Young Et Al-2015-Cochrane Database of Systematic Reviews

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Cochrane Database of Systematic Reviews
Aerobic exercise to improve cognitive function in older people

without known cognitive impairment (Review)
Young J, Angevaren M, Rusted J, Tabet N
Young J, Angevaren M, Rusted J, Tabet N.

Aerobic exercise to improve cognitive function in older people without known cognitive impairment.
Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD005381.
DOI: 10.1002/14651858.CD005381.pub4.
www.cochranelibrary.com
Aerobic exercise to improve cognitive function in older people without known cognitive impairment (Review)
Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
HEADER......................................................................................................................................................................................................... 1
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
BACKGROUND.............................................................................................................................................................................................. 3
OBJECTIVES.................................................................................................................................................................................................. 3
METHODS..................................................................................................................................................................................................... 3
Figure 1.................................................................................................................................................................................................. 5
RESULTS........................................................................................................................................................................................................ 6
Figure 2.................................................................................................................................................................................................. 9
Figure 3.................................................................................................................................................................................................. 10
Figure 4.................................................................................................................................................................................................. 11
Figure 5.................................................................................................................................................................................................. 11
Figure 6.................................................................................................................................................................................................. 12
Figure 7.................................................................................................................................................................................................. 12
Figure 8.................................................................................................................................................................................................. 13
Figure 9.................................................................................................................................................................................................. 13
Figure 10................................................................................................................................................................................................ 14
Figure 11................................................................................................................................................................................................ 14
Figure 12................................................................................................................................................................................................ 15
Figure 13................................................................................................................................................................................................ 15
Figure 14................................................................................................................................................................................................ 15
Figure 15................................................................................................................................................................................................ 16
Figure 16................................................................................................................................................................................................ 16
Figure 17................................................................................................................................................................................................ 17
Figure 18................................................................................................................................................................................................ 17
Figure 19................................................................................................................................................................................................ 18
Figure 20................................................................................................................................................................................................ 18
Figure 21................................................................................................................................................................................................ 19
Figure 22................................................................................................................................................................................................ 19
Figure 23................................................................................................................................................................................................ 20
Figure 24................................................................................................................................................................................................ 20
Figure 25................................................................................................................................................................................................ 20
DISCUSSION.................................................................................................................................................................................................. 21
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 22
ACKNOWLEDGEMENTS................................................................................................................................................................................ 22
REFERENCES................................................................................................................................................................................................ 23
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 30
DATA AND ANALYSES.................................................................................................................................................................................... 52
Analysis 1.1. Comparison 1 Aerobic exercise versus any active intervention, Outcome 1 Cognitive speed.................................... 55
Analysis 1.2. Comparison 1 Aerobic exercise versus any active intervention, Outcome 2 Verbal memory functions (immediate).... 56
Analysis 1.3. Comparison 1 Aerobic exercise versus any active intervention, Outcome 3 Visual memory functions (immediate).... 56
Analysis 1.4. Comparison 1 Aerobic exercise versus any active intervention, Outcome 4 Working memory.................................. 57
Analysis 1.5. Comparison 1 Aerobic exercise versus any active intervention, Outcome 5 Memory functions (delayed)................. 57
Analysis 1.6. Comparison 1 Aerobic exercise versus any active intervention, Outcome 6 Executive functions............................... 58
Analysis 1.7. Comparison 1 Aerobic exercise versus any active intervention, Outcome 7 Perception............................................. 59
Analysis 1.8. Comparison 1 Aerobic exercise versus any active intervention, Outcome 8 Cognitive inhibition.............................. 60
Analysis 1.9. Comparison 1 Aerobic exercise versus any active intervention, Outcome 9 Visual attention..................................... 60
Analysis 1.10. Comparison 1 Aerobic exercise versus any active intervention, Outcome 10 Auditory attention............................. 61
Analysis 1.11. Comparison 1 Aerobic exercise versus any active intervention, Outcome 11 Motor function.................................. 62
Analysis 1.12. Comparison 1 Aerobic exercise versus any active intervention, Outcome 12 Drop-out............................................ 62
Analysis 2.1. Comparison 2 Aerobic exercise versus no intervention, Outcome 1 Cognitive speed................................................. 65
Aerobic exercise to improve cognitive function in older people without known cognitive impairment (Review) i
Informed decisions.
Analysis 2.2. Comparison 2 Aerobic exercise versus no intervention, Outcome 2 Verbal memory functions (immediate)............. 66
Analysis 2.3. Comparison 2 Aerobic exercise versus no intervention, Outcome 3 Visual memory functions (immediate)............. 67
Analysis 2.4. Comparison 2 Aerobic exercise versus no intervention, Outcome 4 Working memory............................................... 67
Analysis 2.5. Comparison 2 Aerobic exercise versus no intervention, Outcome 5 Memory functions (delayed)............................. 67
Analysis 2.6. Comparison 2 Aerobic exercise versus no intervention, Outcome 6 Executive functions........................................... 68
Analysis 2.7. Comparison 2 Aerobic exercise versus no intervention, Outcome 7 Cognitive inhibition........................................... 69
Analysis 2.8. Comparison 2 Aerobic exercise versus no intervention, Outcome 8 Visual attention................................................. 70
Analysis 2.9. Comparison 2 Aerobic exercise versus no intervention, Outcome 9 Auditory attention............................................. 70
Analysis 2.10. Comparison 2 Aerobic exercise versus no intervention, Outcome 10 Motor function............................................... 71
Analysis 2.11. Comparison 2 Aerobic exercise versus no intervention, Outcome 11 Drop-out........................................................ 71
Analysis 3.1. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 1 Cognitive speed......................... 74
Analysis 3.2. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 2 Verbal memory functions 75
(immediate)...........................................................................................................................................................................................
Analysis 3.3. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 3 Visual memory functions 76
(immediate)...........................................................................................................................................................................................
Analysis 3.4. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 4 Working memory....................... 76
Analysis 3.5. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 5 Memory functions (delayed)...... 76
Analysis 3.6. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 6 Executive functions................... 77
Analysis 3.7. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 7 Perception................................. 78
Analysis 3.8. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 8 Cognitive inhibition................... 78
Analysis 3.9. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 9 Visual attention......................... 79
Analysis 3.10. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 10 Auditory attention................. 80
Analysis 3.11. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 11 Motor function....................... 80
Analysis 3.12. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 12 Drop-out................................ 81
Analysis 4.1. Comparison 4 Aerobic exercise versus strength programme, Outcome 1 Verbal memory functions (immediate)...... 82
Analysis 4.2. Comparison 4 Aerobic exercise versus strength programme, Outcome 2 Executive functions................................... 83
Analysis 4.3. Comparison 4 Aerobic exercise versus strength programme, Outcome 3 Perception................................................. 84
Analysis 4.4. Comparison 4 Aerobic exercise versus strength programme, Outcome 4 Cognitive speed........................................ 84
Analysis 5.1. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 1 Cognitive speed........ 87
Analysis 5.2. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 2 Verbal memory 88
functions (immediate)..........................................................................................................................................................................
Analysis 5.3. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 3 Visual memory 89
functions (immediate)..........................................................................................................................................................................
Analysis 5.4. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 4 Working memory...... 90
Analysis 5.5. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 5 Memory functions 90
(delayed)................................................................................................................................................................................................
Analysis 5.6. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 6 Executive functions.... 91
Analysis 5.7. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 7 Perception............... 92
Analysis 5.8. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 8 Cognitive inhibition.... 92
Analysis 5.9. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 9 Visual attention........ 93
Analysis 5.10. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 10 Auditory 94
attention................................................................................................................................................................................................
Analysis 5.11. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 11 Motor function...... 94
Analysis 5.12. Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 12 Drop-out.............. 95
Analysis 6.1. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 1 Cognitive speed................... 97
Analysis 6.2. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 2 Verbal memory functions 98
(immediate)...........................................................................................................................................................................................
Analysis 6.3. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 3 Visual memory functions 99
(immediate)...........................................................................................................................................................................................
Analysis 6.4. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 4 Working memory................. 99
Analysis 6.5. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 5 Memory functions 100
(delayed)................................................................................................................................................................................................
Analysis 6.6. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 6 Executive functions............. 100
Aerobic exercise to improve cognitive function in older people without known cognitive impairment (Review) ii
Informed decisions.
Analysis 6.7. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 7 Cognitive inhibition............. 101
Analysis 6.8. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 8 Visual attention................... 102
Analysis 6.9. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 9 Auditory attention............... 102
Analysis 6.10. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 10 Motor function................. 103
Analysis 6.11. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 11 Drop-out.......................... 103
ADDITIONAL TABLES.................................................................................................................................................................................... 103
APPENDICES................................................................................................................................................................................................. 109
WHAT'S NEW................................................................................................................................................................................................. 116
HISTORY........................................................................................................................................................................................................ 116
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 117
DECLARATIONS OF INTEREST..................................................................................................................................................................... 117
SOURCES OF SUPPORT............................................................................................................................................................................... 117
INDEX TERMS............................................................................................................................................................................................... 117
Aerobic exercise to improve cognitive function in older people without known cognitive impairment (Review) iii
Informed decisions.
[Intervention Review]
Aerobic exercise to improve cognitive function in older people without

known cognitive impairment
Jeremy Young1, Maaike Angevaren2, Jennifer Rusted1, Naji Tabet3
1School of Psychology, University of Sussex, Brighton, UK. 2Research Group Lifestyle and Health, University of Applied Sciences, Utrecht,
Netherlands. 3Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK
Contact address: Jeremy Young, School of Psychology, University of Sussex, Brighton, BN1 9QH, UK. J.Young@sussex.ac.uk.
Editorial group: Cochrane Dementia and Cognitive Improvement Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 4, 2015.
Citation: Young J, Angevaren M, Rusted J, Tabet N. Aerobic exercise to improve cognitive function in older people
without known cognitive impairment. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD005381. DOI:
10.1002/14651858.CD005381.pub4.
ABSTRACT
Background
There is increasing evidence that physical activity supports healthy ageing. Exercise is helpful for cardiovascular, respiratory and
musculoskeletal systems, among others. Aerobic activity, in particular, improves cardiovascular fitness and, based on recently reported
findings, may also have beneficial effects on cognition among older people.
Objectives
To assess the effect of aerobic physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without
known cognitive impairment.
Search methods
We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, the Cochrane Controlled Trials
Register (CENTRAL) (all years to Issue 2 of 4, 2013), MEDLINE (Ovid SP 1946 to August 2013), EMBASE (Ovid SP 1974 to August 2013), PEDro,
SPORTDiscus, Web of Science, PsycINFO (Ovid SP 1806 to August 2013), CINAHL (all dates to August 2013), LILACS (all dates to August 2013),
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch), ClinicalTrials.gov
(https://clinicaltrials.gov) and Dissertation Abstracts International (DAI) up to 24 August 2013, with no language restrictions.
Selection criteria
We included all published randomised controlled trials (RCTs) comparing the effect on cognitive function of aerobic physical activity
programmes with any other active intervention, or no intervention, in cognitively healthy participants aged over 55 years.
Data collection and analysis

Two review authors independently extracted the data from included trials. We grouped cognitive outcome measures into eleven categories
covering attention, memory, perception, executive functions, cognitive inhibition, cognitive speed and motor function. We used the mean
difference (or standardised mean difference) between groups as the measure of the treatment effect and synthesised data using a random-
effects model. We conducted separate analyses to compare aerobic exercise interventions with no intervention and with other exercise,
social or cognitive interventions. Also, we performed analyses including only trials in which an increase in the cardiovascular fitness of
participants had been demonstrated.
Main results
Twelve trials including 754 participants met our inclusion criteria. Trials were from eight to 26 weeks in duration.
Aerobic exercise to improve cognitive function in older people without known cognitive impairment (Review) 1
Informed decisions.
We judged all trials to be at moderate or high risk of bias in at least some domains. Reporting of some risk of bias domains was poor.
Our analyses comparing aerobic exercise to any active intervention showed no evidence of benefit from aerobic exercise in any cognitive
domain. This was also true of our analyses comparing aerobic exercise to no intervention. Analysing only the subgroup of trials in which
cardiorespiratory fitness improved in the aerobic exercise group showed that this improvement did not coincide with improvements in any
cognitive domains assessed. Our subgroup analyses of aerobic exercise versus flexibility or balance interventions also showed no benefit
of aerobic exercise in any cognitive domain.
Dropout rates did not differ between aerobic exercise and control groups. No trial reported on adverse effects.
Overall none of our analyses showed a cognitive benefit from aerobic exercise even when the intervention was shown to lead to improved
cardiorespiratory fitness.
Authors' conclusions
We found no evidence in the available data from RCTs that aerobic physical activities, including those which successfully improve
cardiorespiratory fitness, have any cognitive benefit in cognitively healthy older adults. Larger studies examining possible moderators are
needed to confirm whether or not aerobic training improves cognition.
PLAIN LANGUAGE SUMMARY
Aerobic exercise to improve cognitive function in older people without known cognitive impairment
Aerobic exercise is beneficial for healthy ageing. It has been suggested that the increased fitness brought about by aerobic exercise may
help to maintain good cognitive function in older age. We looked for randomised controlled trials of aerobic exercise programmes for
people over the age of 55 years, without pre-existing cognitive problems, which measured effects on both fitness and cognition. The aerobic
exercise programmes could be compared with no intervention (e.g. being on a waiting list for the exercise group) or with other kinds of
activity (including non-aerobic exercises such as strength or balance exercises, or social activities).
In this Cochrane Review, 12 trials including 754 participants met our inclusion criteria. Eight of the 12 trials reported that the aerobic
exercise interventions resulted in increased fitness of the trained group. However, when we combined results across the trials, we did not
find any significant benefits of aerobic exercise or increased fitness on any aspect of cognition. Many included trials had problems with
their methods or reporting which reduced our confidence in the findings.
We did not find evidence that aerobic exercise or increased fitness improves cognitive function in older people. However, it remains
possible that it may be helpful for particular subgroups of people, or that more intense exercise programmes could be beneficial. Therefore
further research in this area is necessary.
Informed decisions.
BACKGROUND physical activity, cardiovascular fitness and cognitive function in

older people comes from several longitudinal studies (Abbott 2004;
Description of the condition Barnes 2003; Etgen 2010; Laurin 2001; Middleton 2011; Richards
2003; Sturman 2005; van Gelder 2004). However, results from
In 2005, there were over 925 million people worldwide aged 55
training studies by Hill 1993 and Blumenthal 1991 failed to correlate
years or older according to the population database of the United
changes in aerobic power (VO2 max) with changes in cognitive
Nations (WPP 2006). It is predicted that in 10 years this will increase
to over 1.4 billion people. Subjective complaints about cognitive measures. At the same time, trials seldom report combinations of
capacities increase with (older) age (Martin 2003; Newson 2006) and activity, fitness and cognition in a single trial.
an objective decline in cognitive performance accelerates around
Why it is important to do this review
the age of 50 (Salthouse 2003; Verhaeghen 1997), with the exception
of cognitive skills with a large crystallised intelligence component. Previous meta-analyses have reported a robust effect of physical
Research has shown that a regular exercise programme can slow activity on cognitive function in older adults (Colcombe 2003;
down or prevent functional decline associated with ageing and Etnier 1997b; Heyn 2004; Smith 2010), but it remains unclear
improve health in this age group. The physical health benefits for whether improvement in cardiovascular fitness (as reflected by
older people who regularly participate in endurance, balance and cardiovascular parameters such as VO2 max) accounts for the
resistance training programmes are well established. Such health effects of physical activity on cognitive capacity. Physiological
benefits include improved muscle mass, arterial compliance, or psychological mechanisms other than aerobic fitness might
energy metabolism, cardiovascular fitness, muscle strength and still account for the effects found in these meta-analyses. This
overall functional capacity (Lemura 2000). It is suspected that Cochrane Review intends to investigate a hypothesised link
physical activity may also enhance cognitive function (Colcombe between physical activity specifically aimed at the improvement of
2003). cardiorespiratory fitness and cognitive function. Such information
will be useful in the quest to identify interventions that may be
Description of the intervention helpful for healthy ageing and protective against the development
In this Cochrane Review we included the interventions of of neurodegenerative disorders such as Alzheimer's disease.
exercise programmes for older people which aimed to improve
cardiorespiratory fitness, the ability of the circulatory and OBJECTIVES
respiratory to supply oxygen to muscles during sustained physical
To assess the effectiveness of physical activity, aimed at improving
activity, through for example walking, running or cycling. We
cardiorespiratory fitness, on cognitive function in older people
compared their effects with a variety of control interventions:
without known cognitive impairment.
either no intervention or exercise interventions which would
not be expected to enhance cardiorespiratory fitness, such as METHODS
strength or balance programmes, or social or mental activities.
Cardiorespiratory fitness may be assessed in a variety of ways. A Criteria for considering studies for this review
common method is to measure VO2 max, which is the maximal
oxygen uptake measured during exercise on a treadmill or cycle, Types of studies
although other physiological measures or walk times may also be We only included randomised controlled clinical trials (RCTs).
used. Blinding of outcome assessors was not required for inclusion in this
review. We did not apply any language restrictions but trials must
How the intervention might work have been published in peer-reviewed journals.
Research using animal models has provided insight into the
Types of participants
possible cellular and molecular mechanisms that could underlie an
effect of physical activity on cognitive function. Increased aerobic Participants were aged 55 or older and not objectively cognitively
fitness increases oxygen extraction, glucose utilisation and cerebral impaired in any way greater than that expected from age alone.
blood flow (Churchill 2002). Cerebral blood flow meets metabolic Hence, we excluded patients with mild cognitive impairment (MCI)
needs of the brain and removes waste (Lojovich 2010). Increased or any form of dementia and patients with other conditions likely
aerobic fitness also increases Brain-Derived Neurotrophic Factor to be associated with cognitive impairment, such as stroke and
(BDNF) and other growth factors which mediate structural depression. However, we included trials of participants with age-
changes (Cotman 2002; Cotman 2007). For example, BDNF is related illnesses (e.g. osteoporosis, arthrosis) or specific disorders
implicated in neurogenesis, synaptogenesis, dendritic branching (e.g. chronic obstructive pulmonary disease (COPD), heart failure).
and neuroprotection (Lojovich 2010). A preliminary survey of the
literature on human research points towards the same possible Types of interventions
physiological mechanisms that could explain the association We included the physical activity interventions of any programme
between physical activity and cognitive vitality (Aleman 2000; of exercise of any intensity, duration or frequency which was
Brown 2008; Colcombe 2006; Davenport 2012; Erickson 2009; aimed at improving cardiorespiratory fitness. Therefore, trials must
McAuley 2004; Prins 2002). Hence it is hypothesised that have reported at least one objective measure of cardiorespiratory
improvements in cardiovascular (aerobic) fitness mediate the fitness. Acceptable comparator interventions were: no treatment; a
benefits of physical activity on cognitive capacity (Etnier 2007; strength or balance programme; or a programme of social activities
McAuley 2004). Therefore this cardiovascular fitness hypothesis or mental activities. Trials which had both an active comparator
implies that changes in cognitive function are preceded by changes group and a no treatment group could contribute data to the
in aerobic fitness. The evidence for this hypothetical link between
Informed decisions.
'aerobic exercise vs. any active intervention' meta-analyses and to (BIREME), World Health Organization (WHO) International Clinical
the 'aerobic exercise vs. no intervention' meta-analyses. Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch),
ClinicalTrials.gov (https://clinicaltrials.gov) and Dissertation
Types of outcome measures Abstracts International (DAI) up to 24 August 2013 with no language
Trials had to report an objective measure of cardiorespiratory restrictions.
fitness. Acceptable measures included, but were not limited to: VO2
We used a combination of MeSH and free text terms to find records
max, Graded Exercise Test (GXT) rate-pressure product, heart rate of physical activity, including: exercise*, motor activit*, leisure
and blood pressure during modified step test, the Six-Minute Walk activit*, physical fitness, physical endurance, exercise tolerance,
Test (6MWT), 400-metre walk time, and ¼ mile walk time. Where exercise test, aerobic, aerobic capacity, physical activity, physical
trials measured more than one fitness parameter, we preferred capacity, physical performance, training. We have listed the search
the measure that we considered to be the purest measure of strategy details in Appendix 1.
cardiorespiratory fitness, or was previously show to be correlated
with VO2 max, or both. We performed a further search update up to November 2014.
We have inserted the search results into the Studies awaiting
Primary outcomes classification section and will fully incorporate these trials in the
The primary outcome measurement was cognitive function, tested next review update.
with a neuropsychological test (sensitive to changes in cognitive
Searching other resources
function in adults) or test battery (a combination of several
neuropsychological tests). We checked reference lists of the included trials and in reviews of
the literature screened for relevant trials. Also we contacted experts
Secondary outcomes in this area and relevant associations.
Other outcome measures were drop-out, as a measure of
Data collection and analysis
acceptability, and adverse events.
Selection of studies
Search methods for identification of studies
The Cochrane Trials Search Coordinator (ANS) assessed the titles
Electronic searches and available abstracts of all trials identified by the initial search
We searched ALOIS - the Cochrane Dementia and Cognitive and excluded irrelevant trials. Two review authors (JY and NT;
Improvement Group's Specialized Register, Cochrane Central or MA and GA previously) independently assessed full paper
Register of Controlled Trials (CENTRAL), MEDLINE (1946 to copies of reports of potentially relevant trials. We resolved any
August 2013), EMBASE (Ovid SP 1974 to August 2013), PEDro, disagreements on inclusion by discussion and through arbitration
SPORTDiscus, Web of Science (Web of Science platform), PsycINFO by a third review author (JR). Details of the study selection process
(Ovid SP 1806 to August 2013), CINAHL (EBSCOhost), LILACS can be found in Figure 1.
Informed decisions.
Figure 1. Study flow diagram for the August 2013 update search
Informed decisions.
Data extraction and management the addiction field. We assessed the included trials using the criteria
and the method indicated in Higgins 2011.
Two review authors (JY and NT) independently extracted data from
the published reports and JY entered them into RevMan 2014, with Measures of treatment effect
full agreement of the second review author. The summary statistics
required for each trial and each outcome for continuous data were For continuous outcome data, we used the weighted mean
the mean (or mean change from baseline), the standard deviation difference (WMD) if trials used the same cognitive tests and if the
(SD) and the number of participants for each treatment group outcome measurements were on the same scale. We calculated
at each assessment. For cognitive data in which a higher score the standardised mean difference (SMD) in all other cases. For
denotes worse performance (e.g. reaction times, digit vigilance, dichotomous data, such as drop-out, we used the odds ratio (OR).
trail making part A, trail making part B, Stroop interference data
Dealing with missing data
and error rates), we entered the mean as a negative variable. If only
the standard error of the mean was reported, we calculated the SD To allow an intention-to-treat (ITT) analysis, we sought data on
using SD = SE x sqrt(N). For dichotomous data, we extracted the every participant randomised irrespective of compliance, whether
number of participants with each outcome in each group. or not the participant was subsequently deemed ineligible, or
otherwise excluded from treatment or follow-up. If ITT data were
The included articles measured cognitive function using various unavailable in the publications, we sought "on-treatment" data or
rating scales. We grouped neuropsychological tests measuring the data of those who completed the trial, where indicated.
approximately the same construct in a total of eleven categories
(see Table 1; Kessels 2000; Lezak 2004). For each trial, only a single Data synthesis
test was admitted to each category. Where a trial used more than
one test within a category, then first we chose the one which was For each cognitive outcome category, we synthesised the data
used most frequently in the included trials; if not, then the one using a random-effects model. We analysed the possible effects
that had been found to load onto the category in previous factor of aerobic exercise versus any active comparator (strength
analysis (Salthouse 1996) or which we considered closer to the programme, flexibility or balance programme, social or mental
core construct of the category. We chose all included tests prior to programme) and versus no intervention (usual care or waiting list).
extraction of results. Subgroup analysis and investigation of heterogeneity
One trial (Blumenthal 1989) reported results for men and women Heterogeneity was low across all domains in all meta-analyses,
separately in the same paper. In this case, we calculated pooled therefore we did not subgroup analyses to explore heterogeneity.
means and SDs by combining results for both genders.
In order to explore further the potential effects the different forms
Assessment of risk of bias in included studies of exercise, we conducted subgroup analyses which compared
Two review authors (JY, NT) independently evaluated the aerobic exercise with (a) flexibility or balance interventions and
methodological quality of the selected articles using two different (b) strength training. We further explored our hypothesis by
methods. We used the criteria list for quality assessment of non- performing analyses of only those trials in which an increase in
pharmaceutical trials (CLEAR NPT) developed using consensus fitness was demonstrated.
(Boutron 2005). This checklist includes information on sampling As an extension to subgroup analyses, a meta-regression would
method, measurement, intervention and reporting of biases and allow the effect of cardiovascular fitness (VO2 max or any other
limitations (see Table 2). We performed a small pilot exercise to
measure of the degree of aerobic fitness) on cognitive outcomes to
clarify the method with some articles that we already excluded
be investigated. However, we did not consider meta-regression in
from the review process. We calculated Cohen's kappa (K)
this Cochrane Review due to the small number of included trials (<
as a measure of inter-observer agreement, and we relied on
eight trials) in all meta-analyses.
Landis 1977's benchmarks for assessing the relative strength of
agreement. We resolved any discordance in assessment through a
RESULTS
single round of discussion and arbitration by a third review author
(JR). Description of studies
We also used the recommended approach for assessing risk Results of the search
of bias in trials included in Cochrane Reviews, which is
based on the evaluation of six specific methodological domains The August 2013 search identified 352 promising abstracts (see
(namely, sequence generation, allocation concealment, blinding, PRIMSA flow diagram). We identified seven potentially relevant
incomplete outcome data, selective outcome reporting and other theses but these had no associated peer-reviewed publications.
issues). For each trial the six domains are analysed, described as We asked the authors of the theses to provide information on
reported in the trial and a final judgment on the likelihood of bias published data, but none were provided. We examined the full
is provided. This is achieved by answering a pre-specified question texts of 82 articles. We identified 2 new trials for inclusion bringing
about the adequacy of the trial in relation to each domain, such the total number of trials included to 12 trials involving 754
that a judgement of "yes" indicates low risk of bias, "no" indicates participants.
high risk of bias, and "unclear" indicates unclear or unknown risk Included studies
of bias. To make these judgments we used the criteria indicated by
the Cochrane Handbook for Systematic Reviews of Interventions (see We have listed the details of the methods, participants,
Higgins 2011 for a detailed description) and their applicability on interventions and outcomes for each included trial in the
Informed decisions.
Characteristics of included studies table. Also, we have summarized Legault 2011 published a pilot RCT of 73 participants randomly
the intervention types in each trial in Table 2. assigned to a physical activity training group, a cognitive training
group, a combined intervention group or a 'healthy aging' control
Bakken 2001 conducted a small RCT (N = 15) comparing an aerobic group, which we considered an active intervention. We did not
exercise group to a waiting list control group for eight weeks. Both use data from the combined intervention group in this review. The
groups showed slight improvement in a measure of aerobic fitness physical activity training group improved in a fitness measure while
over the course of the trial. The only cognitive outcome parameter the cognitive training and control group did not. Cognitive speed,
was the accuracy index - a test of visual attention. verbal memory, working memory, executive function and cognitive
inhibition were tested in the participants.
Blumenthal 1989 randomised 101 participants to aerobic exercise
training, a yoga/flexibility programme or a waiting list control Moul 1995 recruited 30 participants and randomly assigned them
group over 16 weeks. Participants in the aerobic training group to a walking condition, weight training or control condition, which
only experienced a significant increase in their VO2 max. Outcomes we considered to be a flexibility intervention, for 16 weeks. VO2 max
included tests of cognitive speed, verbal, visual and working significantly increased in the walking group but not in the weight
memory, executive functions, cognitive inhibition, visual and training or control conditions. The Ross Information Processing
auditory attention and motor function. Assessment was used to evaluate changes in cognitive function.
Madden 1989 reported different cognitive outcomes for a subset of Oken 2006 randomised 135 participants into an aerobic group, a
the participants from Blumenthal 1989. We did not included any of yoga group or a waiting list control group for six months. There
the data from this paper in the analyses because Blumenthal 1989 were no significant differences between the groups in their fitness
reported data for the same outcome categories. measure. Cognitive speed, delayed memory functions, executive
functions, visual attention and cognitive inhibition were assessed
Emery 1990a assigned 48 participants to an exercise programme, a
in order to test for effects on cognition.
social activity group or a waiting list control group for 12 weeks. No
effect of the exercise programme on cardiovascular function was Panton 1990 included data on 49 participants randomly assigned
demonstrated. As attrition from the social group was comparable to a walk/jog group, a strength group or a no intervention control
to that of the control group, and attendance for the social group condition for 26 weeks. VO2 max significantly improved for the
was poor overall (ranged from 10% to 94%), the trial authors pooled walk/jog group while there was no significant change for strength
data from the social activity and waiting list control groups (we as well as the control groups. Tests for cognitive speed were
included this pooled group in the 'exercise versus any intervention' performed to analyse cognitive function.
analyses). This trial included tests for cognitive speed and auditory
attention. Whitehurst 1991 recruited 14 participants and randomly assigned
them to an exercise programme or a no intervention control
Fabre 2002 presented data from 32 participants randomly assigned condition for eight weeks. Participants in the exercise group
to an aerobic exercise programme, a mental training programme, significantly increased their VO2 max scores, whereas participants
a combined aerobic/mental programme or a social activity group.
in the control group did not. Choice reaction times were tested for
We did not use data from the combined aerobic exercise/mental
evaluation of cognitive function.
training group in this review. There was a significant increase in
VO2 max in the aerobic training group but no change in the other Excluded studies
two groups. The trial included tests for verbal and visual memory,
perception and executive functions. We have listed details of excluded trials in the Characteristics
of excluded studies table. We excluded trials because they were
Kramer 2001 recruited a total of 174 participants and randomly not RCTs (19), did not use a cognitively normal older population
assigned participants to an aerobic walking group or a stretching (11), did not meet other inclusion criteria (1: Kharti 2001 included
and toning group. The aerobic walking group improved their VO2 depressed participants), did not have objective aerobic fitness
max measures while the stretching and toning group decreased parameters (16), did not have objective cognitive outcomes (5),
their VO2 max measures. The trial authors assessed cognitive assessed cognition during exercise (3), did not have pre- to post-
speed, verbal and visual memory, perception, executive and motor intervention data (4), did not have a non-aerobic control group (2),
functions as well as cognitive inhibition, visual and auditory had not been published (7), the data was published in an already
attention with various cognitive tests. Mean results of the subtests included trial (2), or for other reasons: objective cognitive measures
of the pursuit rotor task, Rey's auditory verbal learning test, spatial were not analysed by group (Emery 1990b) or the control group was
attention and visual search task were summed and divided by the exercising but not given a formal program (Etnier 2001).
number of tasks. SD values of these subtests were pooled.
Risk of bias in included studies
Langlois 2012 randomly assigned 83 participants, ensuring gender We have presented the results of the quality assessment of non-
ratio equivalence, to a 12-week exercise training group or a control pharmaceutical trials (CLEAR NPT) (Boutron 2005) in Table 3.
group that maintained their previous activity levels. Participants The overall methodological quality score of the included trials
in the exercise training group improved in physical fitness, as ranged from 24 to 39 (minimum possible score of 14 points,
measured by the 6MWT, significantly more than controls. Outcomes maximum possible score of 48 points; lower scores denote a better
included tests of cognitive speed, verbal and working memory, methodological quality). For most trials, the blinding treatment
executive functions and inhibition. providers and participants was scored "no, because blinding is not
feasible". Two review authors (JY, NT) calculated Cohen's kappa (K)
Informed decisions.
as a measure of inter-observer reliability after the initial screening other seven trials to be at unclear risk of bias for this item. Four trials
and reached 0.84, almost perfect according to Landis 1977. (Fabre 2002; Legault 2011; Moul 1995; Whitehurst 1991) were judged
to be at low risk of bias for addressing incomplete data. Besides
We have presented the results of our 'Risk of bias' assessment in Legault 2011, in all cases this was due to the fact that there were
the Characteristics of included studies tables and in Figure 2. We no drop-outs from these trials. Legault 2011 reported drop-outs per
only considered one trial to be at low risk of bias for sequence group and analysed using ITT principles. All other eight trials were
generation (Oken 2006). We judged the remaining 11 trials to be at judged being at high risk of bias for this item since they reported
unclear risk of bias for sequence generation. Procedures to ensure drop-outs but either lacked information on the group assignment
allocation concealment were not described in the included papers; of these drop-outs (Panton 1990) or lacked ITT analysis, or both. We
all 12 papers were judged to be at unclear risk of bias in this domain. judged all trials, except Blumenthal 1989, to be at unclear risk of
In all 12 included trials blinding of participants and trainers was bias for selective reporting since there was insufficient information
not feasible. This was unlikely to introduce bias in trainers, so to permit a judgment. Blumenthal 1989 was judged being at high
we considered all 12 trials to be at low risk of bias for blinding risk for this item since data on one pre-specified primary cognitive
trainers. This may have introduced bias in participants, so all 12 outcome was missing. We considered all trials to be at low risk of
trials were judged to be at high risk of blinding of the participants. bias for other potential threats to validity. However, we could not
We judged five trials (Bakken 2001; Legault 2011; Oken 2006; Panton rule out risk of contamination bias, where the control group, on
1990; Whitehurst 1991) to be at low risk of bias for blinding of finding out the purpose of a trial, could have increased their levels
the assessors for the cognitive outcomes because assessment of of aerobic exercise as well.
cognition was by means of computerised tests. We considered the
Informed decisions.
Figure 2. Methodological quality summary: review authors' judgements about each methodological quality item
for each included study.
Informed decisions.
Effects of interventions not the comparison group. We were able to conduct meta-analyses
for all 11 of our pre-specified cognitive domains (Analysis 1.1 to
Aerobic exercise versus any active intervention Analysis 1.11; Figure 3; Figure 4; Figure 5; Figure 6; Figure 7; Figure
Eight trials including 506 participants contributed data on at least 8; Figure 9; Figure 10; Figure 11; Figure 12; Figure 13). There was
one cognitive domain. Duration of the intervention in these trials no evidence of benefit of the aerobic exercise intervention in any
ranged from eight weeks to 26.07 weeks. In six trials, trial authors cognitive domain.
showed an increase in aerobic fitness in the active intervention but
Figure 3. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.1 Cognitive
speed.
Informed decisions.
Figure 4. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.2 Verbal memory
functions (immediate).
Figure 5. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.3 Visual memory
Informed decisions.
Figure 6. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.4 Working
memory.
Figure 7. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.5 Memory
functions (delayed).
Informed decisions.
Figure 8. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.6 Executive
functions.
Figure 9. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.7 Perception.
Informed decisions.
Figure 10. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.8 Cognitive
inhibition.
Figure 11. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.9 Visual
attention.
Informed decisions.
Figure 12. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.10 Auditory
attention.
Figure 13. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.11 Motor
function.
There was no difference in dropout rates between the aerobic

exercise intervention and comparison groups (OR 0.96, 95% CI 0.44
to 2.10; seven trials, 469 participants; Analysis 1.12; Figure 14).
Figure 14. Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.12 Drop-out.
Aerobic exercise versus no intervention but not the comparison group. We were able to conduct meta-
analyses for 10 of our 11 pre-specified cognitive domains, besides
Six trials including 296 participants contributed data on at least
perception (Analysis 2.1 to Analysis 2.10; Figure 15; Figure 16; Figure
one cognitive domain. The duration of the intervention in these
17; Figure 18; Figure 19; Figure 20; Figure 21; Figure 22; Figure 23;
trials ranged from eight to 26.07 weeks. In four trials, trial authors
Figure 24). There was no evidence of benefit of the aerobic exercise
showed an increase in aerobic fitness in the active intervention
intervention in any cognitive domain.
Informed decisions.
Figure 15. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.1 Cognitive speed.
Figure 16. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.2 Verbal memory
Informed decisions.
Figure 17. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.3 Visual memory
Figure 18. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.4 Working memory.
Informed decisions.
Figure 19. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.5 Memory functions
(delayed).
Figure 20. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.6 Executive functions.
Informed decisions.
Figure 21. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.7 Cognitive inhibition.
Figure 22. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.8 Visual attention.
Informed decisions.
Figure 23. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.9 Auditory attention.
Figure 24. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.10 Motor function.
There was no difference in dropout rates between the aerobic

to 4.29; five trials, 267 participants; Analysis 2.11; Figure 25).
Figure 25. Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.11 Drop-out.
Aerobic exercise versus flexibility/balance intervention There was no difference in dropout rates between the aerobic
Analysing only the subgroup of trials in which the aerobic exercise
to 1.72; four trials, 351 participants; Analysis 3.12).
intervention was compared to flexibility or balance control groups,
four trials (351 participants) contributed data on at least one Aerobic exercise versus strength training intervention
cognitive domain (Blumenthal 1989; Kramer 2001; Moul 1995; Oken
2006). Intervention duration in these trials ranged from 16 to 26.07 Subgroup analyses of aerobic exercise intervention compared to
weeks. We were able to conduct meta-analyses on all 11 of our pre- strength training controls was not possible since we could only
specified cognitive domains (Analysis 3.1 to Analysis 3.11). There include one trial in these analyses.
was no evidence of benefit of the aerobic exercise intervention in
any cognitive domain.
Informed decisions.
Fitness improved: aerobic exercise versus any active cardiorespiratory fitness. However, this was not accompanied by
intervention any impact on cognitive function. Several issues need further
consideration. Firstly, the quality of the included trials could
Analysing only the subgroup of trials in which the aerobic exercise
have also affected our results. Reporting of methods in the
intervention was shown to enhance fitness relative to any active
included papers was generally quite poor. For all but one trial, the
intervention control groups, six trials including 367 participants
randomisation methods were unclear. It was not feasible to blind
contributed data on at least one cognitive domain (Blumenthal
participants and trainers, but for most trials it was also unclear if
1989; Fabre 2002; Kramer 2001; Legault 2011; Moul 1995; Panton
outcome assessors were blinded, raising the risk of detection bias.
1990). The duration of the intervention in these trials ranged from
Attrition was poorly reported. No trials had published protocols so
eight to 26.07 weeks. We were able to conduct meta-analyses for all
it was not possible to tell if there was selective reporting of results.
11 of our pre-specified cognitive domains (Analysis 5.1 to Analysis
Of note, no included trials assessed for contamination bias which
5.11). There was no evidence of benefit of the aerobic exercise
could have worked against finding group differences. Secondly,
intervention in any cognitive domain.
with healthy older populations, it is possible that "ceiling effects"
There was no difference in dropout rates between the aerobic prevented detection of cognitive improvement. The risk of this
exercise intervention and comparison groups (OR 1.22, 95% CI 0.66 will depend on the task used and what is being measured. In the
to 2.25; five trials, 330 participants; Analysis 5.12). included papers, no trial author discussed any potential impact of a
ceiling effect on the variables measured. However, there was much
Fitness improved: aerobic exercise versus no intervention variation in each measure included in our analyses which makes
ceiling effects unlikely.
Analysing only the subgroup of trials in which the aerobic
exercise intervention was shown to significantly improve fitness Agreements and disagreements with other studies or
relative to no intervention control groups, four trials involving 183 reviews
participants contributed data on at least one cognitive domain.
Intervention duration in these trials ranged from eight to 26 weeks Five meta-analytic studies and one systematic review published
(Blumenthal 1989; Langlois 2012; Panton 1990; Whitehurst 1991). data based on very similar hypotheses yet failed to find comparable
We were able to conduct meta-analyses for 10 of our 11 pre- results:
specified cognitive domains, besides perception (Analysis 6.1 to
Analysis 6.10). There was no evidence of benefit of the aerobic • Etnier 1997b included 134 articles in their review. Their aim was
exercise intervention in any cognitive domain. to give a comprehensive overview of all literature available with
sufficient information to calculate effect sizes. Therefore, apart
There was no difference in dropout rates between the aerobic from RCTs, the review included several cross-sectional studies.
exercise intervention and comparison groups (OR 1.50, 95% CI 0.50 It reported data on the acute effects of exercise and data on
to 4.50; three trials, Analysis 6.11). strength and flexibility regimens as well as results for younger
age groups and cognitively impaired individuals. The authors
All analyses showed no difference on cognitive test scores between concluded that exercise has a small positive effect on cognition
aerobic exercise groups and either active comparator or no and with the effect size depending on the exercise paradigm, the
treatment groups (controls or waiting list groups). In terms of quality of the trial, the participants and the cognitive tests used
dropout (without Panton 1990, which did not include dropouts by as outcome measures.
group), there were no differences between aerobic exercise and any • van Uffelen 2008 set out to systematically review the effect
of our other intervention groups. Also, no trial included adverse of exercise on cognitive performance in older adults with and
events as an outcome and none of the trial reports made any without dementia. They found 23 papers that met their inclusion
mention of adverse events. criteria. They included strength exercise interventions, trials
which did not assess any fitness parameters and a trial where
DISCUSSION both groups received aerobic training, while this review did not.
Their review observed exercise programmes in healthy older
Summary of main results
adults improved memory, information processing abilities and
This Cochrane Review examined the effect of physical activity executive function.
aimed at improving cardiorespiratory fitness on cognitive function • Smith 2010 meta-analytic review assessed the effects of
in healthy older people without known cognitive impairment. aerobic exercise on cognitive performance. Their criteria
The hypothesis being tested is that physical activity brings about differed from this Cochrane Review in including participants
improvements in cognition which are mediated by increased with MCI, younger participants and trials which did not
cardiovascular (aerobic) fitness (Colcombe 2004; Kramer 1999; assess cardiorespiratory fitness. They also included some
McAuley 2004). If true, this would imply that a physically active unpublished trials. The authors concluded that aerobic exercise
lifestyle resulting in enhanced fitness could positively affect is significantly and positively related to modest improvements
people's cognitive abilities as they age and may even prevent, or in attention and processing speed, executive function and
at least delay, the onset of neurodegenerative disorders such as memory.
Alzheimer's disease. • The meta-analysis presented by Colcombe 2003 included 18
studies. Their aim ("to examine the hypothesis that aerobic
Nine of the 12 included trials reported that aerobic exercise
fitness training enhances the cognitive vitality of healthy
interventions resulted in increased cardiorespiratory fitness of
but sedentary older adults") and exclusion criteria (cross-
the intervention group. This is not unexpected as significant
sectional design, no random assignment, unsupervised exercise
evidence already points to exercise having a beneficial effect on
programme, training lacking in fitness component and an
Informed decisions.
average age below 55) were similar to ours. The reviews differed any relationship between intensity of physical activity and change
in that we excluded trials in which allocation was clearly in cognitive function.
quasi-randomised or did not present any fitness parameter.
We also excluded interventions that were not purely exercise AUTHORS' CONCLUSIONS
and which included participants who were cognitively impaired
or suffered from depression. Colcombe 2003 concluded that Implications for practice
physical activity is beneficial for all analysed cognitive functions. We found no evidence that improving cardiorespiratory fitness
• Etnier 2006 published a meta-analytic review on the relationship necessarily results in improvements in cognitive performance in
between aerobic fitness and cognitive performance. Their healthy older adults without known cognitive impairment.
primary goal was "to provide a statistically powerful test of the
viability of the cardiovascular fitness hypothesis by examining Implications for research
the dose-response relationship between aerobic fitness and
We consider that larger studies with robust methodology exploring
cognition". Their search identified 30 studies which reported
possible moderators are still required to confirm whether or not
data on cross-sectional comparisons, pre-post comparisons and
aerobic training improves cognition in this population.
RCTs. Etnier 2006 included only those studies which assessed
aerobic fitness by maximal, submaximal or a composite We wish to emphasise two important points:
measure of fitness which included VO2 max, whereas we
included all measures of aerobic fitness. We imposed a lower 1. Our review includes results from as many as 40 different
age limit and did not include trials on depressed participants cognitive tests. This is already a smaller sample of tests than
whereas Etnier 2006 included all ages and at least one trial on the absolute total reported in the included trials (tests were lost
depressed subjects. Etnier 2006 included unpublished master from analyses in order to avoid double representation of trials
theses and doctoral dissertations, whereas we only included within cognitive categories). A broad battery of tests can give
data published in peer reviewed journals. Post-test comparisons insight into the specificity of physical activity effects. At the same
showed no significant relationships between aerobic fitness time, too great a number of cognitive tests can be confusing and
and cognitive performance. For the exercise groups, increased obscure overall effects. We would recommend that researchers
fitness was associated with worse cognitive function. Age in the field seek agreement on a smaller battery of cognitive tests
interacted with fitness and was a significant negative predictor to use in order to increase comparability between trials. This
of cognitive performance for older adults. smaller core-set of cognitive tests should incorporate measures
of key cognitive domains which are important both scientifically
Although we did not identify any relationship between physical and clinically.
activity or cardiorespiratory fitness and cognitive function, it 2. Any intervention that is to be effective against age-related
is possible that certain subgroups of the population, such as cognitive decline should be assessed over a significant period of
those starting from a lower baseline of fitness, could react time. A limitation of the included RCTs is the lack of long-term
differently to aerobic training. Other factors which might influence follow-up (with an average duration of 15.62 weeks). Longer-
the relationship include: age, frequency of cognitive activities term intervention trials would be very valuable in the future.
(Christensen 1993; Hultsch 1993; Hultsch 1999; Lachman 2010;
Marquine 2012; Wilson 1999; Wilson 2005), social network (Crooks ACKNOWLEDGEMENTS
2008; Seeman 2001), and adherence to a Mediterranean diet
(Panagiotakos 2007; Tangney 2011). The search for possible We thank Jenny McCleery, Co-ordinating Editor of the Cochrane
subgroups has provided some promising results (examples in Dementia and Cognitive Improvement Group (CDCIG), for
Etnier 2007; Podewils 2005; Schuit 2001). assistance. We are grateful to Anna Noel-Storr, Trials Search
Coordinator, for her initial assessment of trials identified by
It is possible that the intensity of physical activities is important searches in this iteration. We thank Sue Marcus, Managing Editor
(Angevaren 2007; Brown 2012; Tierney 2010; van Gelder 2004) which of CDCIG, for assistance. Also, we thank Geert Aufdemkampe, HJJ
may have implications for the effectiveness of some of the training Verhaar, A Aleman and Luc Vanhees for their help with a previous
programmes in the included RCTs. However, Smith 2010 did not find version of this manuscript.
Informed decisions.
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Littbrand 2006 {published data only}
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Informed decisions.
Palleschi 1996 {published data only} Rosendahl 2006 {published data only}
Palleschi L, Vetta F, De Gennaro E, Idone G, Sottosanti G, Rosendahl E, Lindelöf N, Littbrand H, Yifter-Lindgren E,
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van Uffelen 2007 {published data only}
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Wilbur 2005 {published data only} Angevaren 2007

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Williams P, Lord SR. Effects of group exercise on cognitive Barnes 2003
functioning and mood in older women. Australian and New Barnes DE, Yaffe K, Satariano WA, Tager IB. A longitudinal
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healthy older adults. Journal of the American Geriatrics Society
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Williamson JD, Espeland M, Kritchevsky SB, Newman AB,
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randomized trial of physical activity: results of the lifestyle Boutron I, Moher D, Tugwell P, Giraudeau B, Poiraudeau S,
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of Gerontology. Series A: Biological sciences and medical sciences nonpharmaceutical trial (CLEAR NPT) was developed
2009;64(6):688-94. using consensus. Journal of Clinical Epidemiology
2005;58(12):1233-40.
Winter 2007 {published data only}
Winter B, Breitenstein C, Mooren FC, Voelker K, Fobker M, Brown 2008
Lechtermann A, et al. High impact running improves learning. Brown AD, McMorris CA, Longman RS, Leigh R, Hill MD,
Neurobiology of Learning & Memory 2007;87(4):597-609. Friedenreich CM, et al. Effects of cardiorespiratory fitness and
cerebral blood flow on cognitive outcomes in older women.
Zlomanczuk 2006 {published data only} Neurobiology of Aging 2008;31(12):2047-57.
Zlomanczuk P, Milczarek B, Dmitruk K, Sikorski W, Adamczyk W,
Zegarski T, et al. Improvement in the face/name association Brown 2012
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4):417-24. cognitive performance in the elderly. Translational Psychiatry
2012;2:e191.
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impairment. Cochrane Database of Systematic Reviews 2008, cognitive function in older people without known cognitive
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CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Bakken 2001
Methods Parallel-group RCT: 1 intervention group and 1 control group.
At randomisation 15 enrolled; 8 in the aerobic exercise group, 7 in the control group.
Follow-up: 8 weeks
Participants 10 participants (4 males, 6 females) in the age range of 72 to 91 years from a senior housing complex in
Minneapolis, Minnesota.
Inclusion criteria: > 65 years of age with no history of pulmonary disease, recurring falls, orthopaedic
limitations or acute arthritis in the hands.
Interventions Aerobic exercise: 1 hour sessions for 3 sessions per week for 8 consecutive weeks. 10 minutes of warm-
ing up, aerobic conditioning period that increased in duration and intensity (callisthenics, walking and
cycling) systematically each week, 10 minutes of cooling down. Subjects heart rates did not exceed the
upper limit of their THRR*.
Control: continued their normal everyday routine, which did not include any aerobic exercise accord-
ing to the subjects report.
Outcomes AI (Accuracy Index by finger movement)

Resting heart rate
Resting systolic BP
Resting rate-pressure product
GXT test heart rate**
GXT test systolic BP
GXT test RPP (Rate-Pressure product)
Notes Testing took place at the University of Minnesota.
*THRR: (Karvonen) training HR = resting HR + [0.60-0.75 (HRR)].

HRR = age-predicted max HR - resting HR
**GXT: submaximal graded exercise tolerance test. Stage 1; stepping back and forth on the ground at a
frequency of 20 mounts per minute for 3 minutes. Stage 2: stepping up and down a 10.16 cm high step.
Stage 3: stepping up and down a 20.32 cm high step. Stage 4: stepping up and down a 30.48 cm high
step.
RPP; rate-pressure product = systolic BP multiplied by heart rate. A decrease in RPP is a quantitative
measure of aerobic training.
Both groups showed slight increases in RPP from pre-test to post-test.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Unclear risk No information provided.

tion (selection bias)
Allocation concealment Unclear risk No information provided.

(selection bias)
Informed decisions.
Bakken 2001 (Continued)
Blinding (performance High risk Participants were not blinded to their group assignment, but it was not feasi-
bias and detection bias) ble to do so.
Participants
Blinding (performance Low risk It is not feasible that the trainers were blinded to the condition but this non-
bias and detection bias) blinding was unlikely to introduce bias.
Trainers
Blinding (performance Low risk Cognition was assessed with a computer and therefore adequately blinded. At
bias and detection bias) the same time the researchers where unaware of the group assignment of the
Outcome assessors participants.
Incomplete outcome data High risk 3/8 participants were lost from the exercise condition, 2/7 were lost in the con-
(attrition bias) trol group. Main outcomes were not analysed according to the ITT principle.
All outcomes
Selective reporting (re- Unclear risk Insufficient information.

porting bias)
Other bias Low risk However, we cannot rule out contamination bias.
Blumenthal 1989
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 101 participants (50 males and 51 fe-
males) were randomised either to aerobic exercise (N = 33), yoga/flexibility (N = 34) or control (N = 34).
Follow-up: 16 weeks
Participants 101 participants aged 60 to 83 years

Inclusion criteria: free from clinical manifestations of coronary disease assessed by medical history,
physical examination, bicycle ergometry exercise testing.
Exclusion criteria: positive ECG during exercise testing, evidence of coronary artery disease, asthma,
pulmonectomy, uncontrolled hypertension, beta-blocker therapy.
Interventions Aerobic exercise: 3 supervised sessions per week for 16 weeks. Training based on 70% of max heart rate
achieved on exercise test. 10 minutes of warming up, 30 minutes of bicycle ergometry, 15 minutes of
brisk walking/jogging and arm ergometry, 5 minutes of cooling down.
Yoga/flexibility: 2 supervised sessions a week for 60 minutes over 16 weeks.
Controls: not to change their physical activity habits and especially not to engage in any aerobic exer-
cise for the trial period.
Outcomes Tapping (dominant/non-dominant)

Digit span (forward / backward)
Benton Revised Visual Retention test (correct/error)
Story Recall of the Randt Memory test (immediate) - data on the delayed Story Recall of the Randt
Memory test could not be traced by the authors.
Selective reminding test (total/intrusions)
Trail making (part B)
Digit Symbol substitution
2 & 7 test (digits/letters)
Stroop colour word
Stroop interference
Verbal fluency
Non-verbal fluency
VO2 max
AT
Informed decisions.
Blumenthal 1989 (Continued)
Notes Testing took place at the Duke University Medical Center.
A summary combination of the scores on both 2&7 test (letters and digits) was calculated and SDs were
pooled and used in analysis.
Subjects in the aerobic training group experienced a significant 11.6% increase in their VO2 max (from
19.4 to 21.4 mL/kg/min), whereas the participants in the yoga/flexibility and control groups experi-
enced a 1 to 2% decrease in VO2 max (from 18.8 to 18.7 mL/kg/min and 18.5 to 17.9 mL/kg/min, respec-
tively).
Risk of bias


(selection bias)
Participants
Trainers
Blinding (performance Unclear risk Insufficient information is provided to judge the blinding of the cognitive out-
bias and detection bias) comes.
Outcome assessors
Incomplete outcome data High risk 2/33 participants were lost from both the aerobic group and yoga/flexibility
(attrition bias) group and 2/34 the control group. Main outcomes were not analysed accord-
All outcomes ing to the ITT principle.
Selective reporting (re- High risk The methods section describes assessment of the Story Recall of the Randt
porting bias) Memory test after 30 minutes delay. Data on this subtest could not be traced
by the authors.
Other bias Low risk Although contamination bias could not be ruled out.
Emery 1990a
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 48 subjects (8 males and 40 females)
were randomly assigned to an aerobic exercise programme (N = 15), social activity group (N = 15) or a
control group (N = 18).
Follow-up: 12 weeks
Participants 48 participants aged 61 to 86 years from a metropolitan inner-city community.

Inclusion criteria not described.
Exclusion criteria not described.
Interventions Exercise: 3 sessions per week for approximately 60 minutes. 10 to 15 minutes of stretching exercises
followed by 20 to 25 minutes of aerobic exercise (at 70% of age-adjusted max = 220-age), including
Informed decisions.
Emery 1990a (Continued)

rapid walking as well as rhythmic muscle strengthening exercises (e.g. repeatedly standing up and sit-
ting down). 5 minutes of cooling down with dancing and light exercises.
Social activity: 3 sessions per week for 60 minutes. Participation in non-physical activities (card games,
art projects, political discussion groups, watching films).
Controls: not described.
Outcomes Digit Symbol substitution

Digit Span
Copying Words
Copying Numbers (digit/sec)
Weight (kg)
Resting HR
Resting blood pressure (syst/diast)
BP during modified step test
HR during modified step test
Sit-and-reach test
Resting heart rate, maximum heart rate and systolic/diastolic blood pressure indicated no significant
differences between the groups. Both groups showed a significant time main effect decrease in dias-
tolic blood pressure, other measures indicated no significant effects.
Risk of bias


(selection bias)
Participants
Trainers
Blinding (performance Unclear risk Insufficient information provided to assess the blinding of the cognitive out-
bias and detection bias) come measures.
Outcome assessors
Incomplete outcome data High risk 1/15 participants was lost from the aerobic group, 4/15 from the social group
(attrition bias) and 4/18 from the control group. Main outcomes were not analysed according
All outcomes to the ITT principle.
Selective reporting (re- Unclear risk Insufficient information provided.

porting bias)
Informed decisions.
Fabre 2002
Methods Parallel-group RCT: 3 intervention groups and 1 control group. 32 participants (5 males and 27 females)
at randomisation; each group (physical training, memory training, combined physical/memory training
and controls) contained 8 subjects.
Follow-up: 8 weeks
Participants 32 participants in the age range of 60 to 76 years "from clubs".

Inclusion criteria are not described. Exclusion criteria: positive ECG during exercise testing, present de-
pression, could not breathe through the tube during exercise testing, various other reasons such as dis-
ease during training.
Interventions Physical training: two supervised 1 hour exercise sessions per week for 8 weeks: walking and running
to maintain target heart rate (target heart rate corresponded to the ventilatory threshold). 5 minutes of
warming up, 45 minutes of walking/running, 10 minutes of cooling down.
Memory training: 90 minutes of sessions once a week for 8 weeks. 15 minutes of explaining, Israel's
method in core.
Combined physical training and memory training.
Controls: no training whatsoever.
Outcomes Memory quotient (= total score of al WAIS subtests)

Paired associates learning
Digit span forward
Logical memory immediate recall
Orientation
General information
Mental control
Visual reproductions
VO2 max
VO2 max at Vth
Max O2 pulse
Max O2 pulse at Vth
Notes Testing took place at the University of Montpellier.
The physical training resulted in an average significant increase in VO2 max of 12% (from 1350 to 1630
mL/min) and 11% (from 1510 to 1625 mL/min) in the aerobic training group and the combined aero-
bic/mental group, respectively. The VO2 max scores of the participants in the other two groups were
unchanged compared to initial values (mental training group from 1060 to 999 mL/min and controls
from 1256 to 1265 mL/min).
Risk of bias


(selection bias)
Participants
Informed decisions.
Fabre 2002 (Continued)

Trainers
Outcome assessors
Incomplete outcome data Low risk All participants completed the trial.
(attrition bias)
All outcomes

porting bias)
Kramer 2001
Methods Parallel-group RCT: 1 aerobic walking intervention group and 1 stretching/toning control group.174
participants at randomisation. The trial was completed by 124 individuals; 58 (13 men) in the aerobic
group and 66 (20 men) in the stretching and toning group.
Follow-up period: 6 months.
Participants 124 participants aged 60 to 75 years of age.

Inclusion criteria: aged 60 to 75 years, sedentary (no physical activity in the preceding 6 months), capa-
ble of performing exercise, physicians examination and consent to participate, successful completion
of graded exercise test without evidence of cardiac abnormalities, initial depression score on the GDS
below clinical level, no history of neurologic disorders, corrected (near & far) acuity of 20/40 or better,
fewer than three errors on the Pfeiffer Mental Status questionnaire.
Exclusion criteria: younger than 60 years, self-reported activity on a regular basis (2 times a week) in
the preceding 6 months, any physical disability that prohibits mobility, non-consent of physician, evi-
dence of abnormal cardiac responses during graded exercise testing, depression score on the GDS in-
dicative of clinical depression, history of neurologic disorders, corrected (near & far) acuity greater than
20/40, more than three errors on the Pfeiffer questionnaire.
Interventions Aerobic walking exercise: 3 supervised sessions per week for 6 months. Warming up, 40 minutes of
brisk walking (gradually beginning at 10 to 15 minutes up to 40 minutes), cooling down. Initial exercise
was performed at 50 to 55% of VO2 max and increased to 65 to 70% of VO2 max.
Stretching and toning: 3 times a week supervised sessions for 6 months. The programme emphasized
stretches for all the large muscle group of the upper and lower extremities. Each stretch was held for 20
to 30 seconds and repeated 5 to 10 times. Each session was proceeded and followed by 10 minutes of
warm-up and cooling down.
Outcomes Visual search task

Response compatibility task
Task switching paradigm
Stopping paradigm
Spatial attention task
Rey auditory verbal learning test
Pursuit rotor task
Self-ordered pointing task
Spatial working memory
Verbal working memory
Face recognition task
Digit-digit and digit-symbol tests
Forward and backward digit span
Informed decisions.
Kramer 2001 (Continued)

VO2 max (mL/kg/min)
Time on treadmill (min)
Rockport 1-mile walk (min)
Notes Testing took place at the University of Illinois at Urbana-Champaign.
The physical training resulted in improvements of 5.1% on VO2 max measures (from 21.5 to 22.6 mL/
kg/min). The toning group showed a 2.8% decrease in VO2 max scores (from 21.8 to 21.2 mL/kg/min).
Risk of bias


(selection bias)
Participants
Trainers
Outcome assessors
Incomplete outcome data High risk 25/83 subjects from walking group and 25/91 subjects from stretching/toning
(attrition bias) group were dropped from the trial because of withdrawal from the training
All outcomes protocol or incomplete data. These participants did not differ in demographic
characteristics from those who completed the trial. Main outcomes were not
analysed according to the ITT principle.

porting bias)
Langlois 2012
Methods Parallel-group RCT: 1 one exercise training intervention group and 1 waiting list control group. 83 par-
ticipants at randomisation, randomised ensuring gender ratio equivalence: 43 in the intervention
group, 40 in the control group.
Follow-up: 3 months
Participants 72 participants aged 61 to 89.

Inclusion criteria: assessed via complete geriatric assessment as able to perform exercise programme
at low risk.
Exclusion criteria: limitations to undertaking exercise programme, MMSE < 25, or GDS > 10, or both.
Informed decisions.
Langlois 2012 (Continued)
Interventions Physical exercise training group: 12 weeks of 1 hour exercise 3 days/week conducted in supervised 3 to
5 participant subgroups. 10 mins stretching and balancing warm up, 10 to 30 mins aerobic workout, 10
mins strength training, 10 mins cool down. Intensity and duration of aerobic workout increased individ-
ually using modified Borg RPE reaching moderate to hard intensity.
Control group: maintain level of activity during period and were offered physical training programme
after trial.
Outcomes MMSE
WAIS-III Similarities
WAIS-III Digit-Symbol Coding
Trailmaking part A
Trailmaking part B
modified Stroop Colour-Word Test
WAIS-III Letter-Number Sequencing
Digit Span Backwards
Rey Auditory Verbal Learning Task
6MWT
modified Physical Performance Test
Timed Up and Go Test
Gait speed (comfortable and maximum)
Notes Testing took place at the Université du Québec à Montréal.
There was a significantly larger improvement in the exercise training group in comparison to the con-
trol group in the 6MWT.
Risk of bias


(selection bias)
Participants
Trainers
Outcome assessors
Informed decisions.
Langlois 2012 (Continued)
Incomplete outcome data High risk 7/43 participants was lost from the intervention group, 4/40 from the from the
(attrition bias) control group. Main outcomes were not analysed according to the ITT princi-
All outcomes ple.

porting bias)
Legault 2011
Methods Parallel-group RCT: 3 intervention groups and 1 control group. 73 participants at randomisation, 18
(10 female) were put into the physical activity training group, 18 (8 female) into the cognitive training,
19 (12 female) into the combined intervention group, and 18 (7 female) into the healthy aging control
group.
Follow-up period: 4 months.
Participants 73 participants, aged 70 to 85 years of age that were community-dwelling.
Inclusion criteria: aged 70 to 85, identified as "individuals who were appropriate candidates for physi-
cal activity and cognitive training and who appeared likely to adhere to interventions and data collec-
tion protocols" as detailed in a previous paper.
Exclusion criteria: Related to Physical Activity: Severe rheumatologic or orthopedic diseases, severe pul-
monary heart disease, actively participating in a formal exercise programme within the past month
(> 30 min/week), severe cardiac disease, clinically significant aortic stenosis, history of cardiac arrest
which required resuscitation, use of cardiac defibrillator or uncontrolled angina. Other significant co-
morbid disease that would impair ability to participate in the exercise based intervention. Receiving
physical therapy for gait, balance or other lower extremity training. Serious conduction disorder, un-
controlled arrhythmia. Pulmonary embolism or deep venous thrombosis within past 6 months. Hip
fracture, hip or knee replacement, or spinal surgery within past 4 months. Severe hypertension.
Related to Cognition: Neurological disease, stroke that required hospitalisation, Parkinson's, multi-
ple sclerosis, Amyotrophic Lateral Sclerosis, or MCI. Telephone interview for cognitive status ≤ 31. Cur-
rent use of cognitive enhancing prescription or investigational medications. History of participation
in a cognitive training programme in the last two years. 3MSE score < 88 (< 80 for ≤ 8 years education).
Scores ≥ 2 SDs below normal on memory or non-memory domain tests (speed of processing and verbal
fluency). Other significant factors that may affect the ability for cognitive training, including a history
of head trauma resulting in a loss of consciousness, current use of benzodiazepines, hypnotic or anti-
cholinergic agents. Stroke within past 4 months. Baseline Geriatric Depression Scale score ≥ 8.
Related to trial design or adherence: Age < 70 or > 85 years. Unwillingness to be randomized to any of
the four intervention conditions. Failure to provide the name of a personal physician. Living in a nurs-
ing home. Terminal illness with life expectancy less than 8 months. Unable to communicate because of
severe hearing loss or speech disorder. Severe visual impairment. Excessive alcohol use (> 14 drinks per
week). Member of household is already enrolled. Lives distant from the trial site or is planning to move
out of the area in the next year or leave the area for more than one month during the next year. Other
temporary intervening events, such as sick spouse, bereavement or recent move. Participation in an-
other intervention trial. Inability to commit to intervention schedule requirements. Failure to provide
informed consent.
Interventions Physical activity training: centre-based and home-based sessions aimed at aerobic and flexibility train-
ing targeting duration of 150 minutes/week. Two centre-based sessions per week for four months, fo-
cus on walking (or other endurance activity if contraindicated) with explicit intent of improving cardio-
vascular fitness. Centre-based sessions approximately 60 minutes - 40 minutes walking, 20 minutes
flexibility. Tailored home-based walking 1 to 2 sessions per week for first month and encouraged to
slowly increase duration, speed and frequency to achieve 150 min/week goal.
Informed decisions.
Legault 2011 (Continued)

Cognitive training: four consecutive 10 to 12 min sessions per day, administered two times per week for
two months, then one time per week for two additional months at centre via computer, where partic-
ipants studied a list of 30 words, then were given a recognition test consisting of the 30 studied words
and 30 new words with each new word repeated once, and asked to respond "yes" to trial words or
"no" to new words. Intervals between the first and second presentation of new words increased as par-
ticipants reached accuracy thresholds.
Combined physical activity and cognitive training: received both, cognitive was delivered prior to phys-
ical activity to avoid impact of fatigue.
Controls: weekly lectures based on health education, topics such as medications, foot care, travelling
and nutrition.
Outcomes Trailmaking part A

Trailmaking part B
Hopkins Verbal Learning Test
2-Back
Flanker Task
400-metre walk time
Notes Testing took place at Wake Forest University.
400-metre walk times for the physical activity training group decreased by 5.31 seconds and were not
different from the combined intervention group. Walk times for the cognitive training group and the
'healthy ageing' group did not improve.
Risk of bias


(selection bias)
Participants
Trainers
Blinding (performance Low risk Trial was "single-blinded", since it is not possible to blind participants, out-
bias and detection bias) come assessors must have been blinded.
Outcome assessors
Incomplete outcome data Low risk All analyses conducted according to ITT principles. 2/18 participants in the
(attrition bias) physical activity group were excluded because they did not return for the 4-
All outcomes month visit. 1/18 in the physical activity group and 1/19 in the combined inter-
vention group were excluded for not attending any of the centre-based train-
ing sessions.

porting bias)
Informed decisions.
Madden 1989
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 85 participants (44 males and 41 fe-
males) at randomisation; 28 in the aerobic group, 30 in the yoga group and 27 served as controls.
Follow-up: 16 weeks.
Participants Participants were 60 to 83 years of age.

Inclusion criteria: free of medical conditions that would preclude a programme of either aerobic exer-
cise or yoga.
Exclusion criteria: uncontrolled hypertension, diabetes, or coronary heart disease, use of beta-block-
ers or psychotropic medication.
Interventions Aerobic exercise: 3 supervised sessions per week for 16 weeks. 10 minutes of warming up, 30 minutes of
cycling, 15 minutes of brisk walking or jogging or both, 5 minutes of cooling down. All exercise was per-
formed in target (training) heart range (70% of max during initial exercise test).
Yoga: 2 times a week 60 minutes of supervised yoga sessions for 16 weeks.
Control: no change to their physical activity habits for the length of the trial.
Outcomes Letter search RT task (short-term memory)

Word comparison RT task (long-term memory)
VO2 max
Aerobic capacity remained constant for the yoga and control groups between pre- and post-test (re-
spectively from 18.8 to 18.6 mL/kg/min and from 19.1 to 18.6 mL/kg/min), whereas the aerobic exercise
group showed a significant 11% increase in VO2 max (from 19.7 to 21.9 mL/kg/min)
Risk of bias


(selection bias)
Participants
Trainers
Outcome assessors
Incomplete outcome data High risk 3/28 were lost from the exercise group, 2/30 from the yoga group and 1/27
(attrition bias) from the controls. Main outcomes were not analysed according to the ITT prin-
All outcomes ciple.
Informed decisions.
Madden 1989 (Continued)

porting bias)
Moul 1995
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 30 participants (11 males, 19 females),
the walking, weight training and control group all contained 10 participants.
Participants 30 participants aged 65 to 72 years.

Inclusion criteria: nondiseased (no current symptoms or signs suggestive of heart disease), non active
(defined as < 2 moderate to vigorous aerobic or resistance training sessions of > 20 minutes per week).
Interventions Walking: 5 sessions per week. Walking 30 minutes at 60% of HRR (as determined by treadmill testing).
Walking duration was increased 2 minutes per week until they reached 40 minutes and HRR were ad-
justed after 8 weeks of training to 65% of HRR.
Weight training: 5 sessions per week of upper and lower body exercises on alternate days of the week.
Abdominal crunches and back extensions were performed in each session. Weight group employed a
daily adjusted progressive resistive exercise programme (DAPRE) using weights.
Controls: 5 sessions per week mild stretching exercises for 30 to 40 minutes. Minimal challenge to the
cardiovascular or muscular systems.
Outcomes Immediate Memory (Ross Information Processing Assessment)

Recent Memory (RIPA)
Temporal Orientation (RIPA)
Problem Solving and abstract reasoning (RIPA)
Organization (RIPA)
Auditory Processing (RIPA)
Weight (kg)
Sum of seven skinfolds (mm)
VO2 max (mL/kg/min)
Time on treadmill (min)
Ventilation (mL/min)
RER
Knee extension (lb)
Elbow flexion (lb)
Notes Testing took place at the Human Performance Laboratory and Athletic Training Laboratory, Appalachi-
an State University.
Post-test data revealed that the subjects in the walking condition significantly increased their VO2 max
by an average of 16% (from 22.4 to 26.6 mL/kg/min), whereas there were no significant changes in VO2
max for the other two groups (weight training group from 21.4 to 20.4 mL/kg/min and controls from
20.9 to 19.3 mL/kg/min).
Risk of bias

Informed decisions.
Moul 1995 (Continued)

(selection bias)
Participants
Trainers
Outcome assessors
(attrition bias)
All outcomes

porting bias)
Oken 2006
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 135 participants were randomised in a
yoga class (N = 47), exercise group (N = 44) or a wait-list control group (N = 44).
Follow-up: 6 months.
Participants Participants were healthy adults in the age of 65 to 85 years.
Inclusion criteria: other than age not described.
Exclusion criteria: subjects were screened for significant medical problems, had a physical examina-
tion and routine ECG to ensure the safety of the intervention and to exclude participants with pathol-
ogy with might impair cognition. Subjects were excluded for the following reasons: insulin-dependent
diabetes, uncontrolled hypertension, evidence of liver or kidney failure, significant lung disease, alco-
holism or other drug abuse, symptoms or signs of congestive heart failure, symptomatic ischemic heart
disease, or significant valvular disease and significant visual impairment. Subjects also were excluded
if they were actively practicing yoga or had taken a yoga or tai-chi class in the last 6 months or if they
were regularly performing aerobic exercise more than 210 minutes per week.
Interventions Yoga was taught in one class per week along with home practice. The yoga classes were 90 minutes in
duration and designed by a certified Iyengar yoga teacher, an Iyengar trained teacher and a physician.
Over all weeks, eighteen poses were taught. Each class ended with a 10-minute deep relaxation period
with the participant lying supine. Daily home practice was strongly encouraged and participants were
encouraged to honour their individual limits.
A certified personal trainer with experience in the geriatric population directed the aerobic exercise in-
tervention arm of the trial. The aerobic intervention consisted of 1 class per week along with home ex-
ercise. The aerobic exercise consisted of walking on an outdoor 400-metre track for endurance train-
ing. The 1-hour class began with walking 2 laps to warm up and then progressed to mild leg stretches.
Intensity of exercise was determined by heart rate and modified Borg Rate of Perceived Exertion scale
(Borg CR10 Scale). Participants wore a heart-rate monitor, and target heart rate was initially estimated
as 70% of maximum based on morning resting heart rate and age. Participants were instructed to exer-
Informed decisions.
Oken 2006 (Continued)

cise at a level of 6/7 on the Borg scale. Based on perceived exertion, the heart rate target was adjusted
slightly. Participants were strongly encouraged to exercise daily at least 5 times per week in addition to
the weekly class session.
Participants in the wait-list control group received no intervention.
Outcomes Stroop colour word
Covert orienting of spatial attention
Simple RT (msec)
Choice RT (msec)
10-words learning task (delayed recall)
Letter-number sequencing
SF-36
Stanford sleepiness scale (SSS)
Profile of mood states (POMS)
Multidimensional fatigue inventory (MFI)
Centre for epidemiologic studies depression scale (CESD-10)
State-trait anxiety inventory
One-leg stand (sec)
Chair sit and reach (cm)
Sit and stand (sec)
¼ mile walk (sec)
Notes Testing took place at the Oregon Health and Science University.
After 6 months there were no significant differences in time at a ¼ mile walk between all three groups.
Risk of bias
Random sequence genera- Low risk "Subjects were randomly assigned to treatment groups in this study with a
tion (selection bias) planned modified minimization scheme".

(selection bias)
Participants
Trainers
Blinding (performance Low risk Outcome assessors were adequately blinded.

bias and detection bias)
Outcome assessors
Informed decisions.
Oken 2006 (Continued)
Incomplete outcome data High risk 9/47 dropped out from yoga, 6/44 from exercise and 2/44 from the wait-list
(attrition bias) group. ITT analysis was not performed. Quote: "No attempt was made to input
All outcomes missing variables".

porting bias)
Panton 1990
Methods Parallel-group RCT: 2 intervention groups and 1 control group. 57 participants were randomised in a
walk/jog group, a strength group and a control group. Analyses were performed on 17 participants in
the walk/jog group, 20 participants in the strength group and 12 controls.
Participants were not blinded; it is unclear whether the outcome assessor and the caregiver were
blinded.
Participants Participants were retired professionals from the university community of Gainesville, FL and 70 to 79
years of age.
Inclusion criteria: sedentary non-smokers who had no contraindications to exercise testing or training.
Free of any overt evidence of coronary artery disease and other conditions that would limit their partic-
ipation in a vigorous exercise programme as tested with a diagnostic graded exercise test (using a mod-
ified Naughton protocol).
Exclusion criteria were not described.
Interventions The walk/jog group participated in three exercise sessions per week for the duration of the trial. All
training sessions were preceded by 5 to 10 minutes of stretching and warm-up and ended with 5 min of
cool-down exercises. Initially, participants started walking/jogging for 20 minutes at 50% of their max-
imal heart rate reserve (HRRmax). The duration was increased by 5 min every 2 weeks until the partic-
ipants walked for 40 minutes. Training intensity was gradually increased until participants could walk
at 60 to 70% of their HRRmax. During the 14th week of training exercise intensity was further increased
by alternating fast walk/moderate walk or fast walk/slow jog intervals. Five participants increased their
training intensity by increasing the slope of the treadmill. By the 26th week of training, all participants
performed at 85% of HRRmax for 35 to 45 min.
Participants in the strength group participated in 30 min sessions, 3 times a week for 26 weeks. Work-
outs consisted of one set of 10 variable resistance Nautilus exercises (leg, arm and torso muscles). Dur-
ing the first 13 weeks, participants used light to moderate weights and performed 8 to 12 repetitions for
each exercise. During the last 13 weeks, resistance was increased substantially and participants were
encouraged to train to volitional muscular fatigue. When participants could complete 12 or more repe-
titions, the resistance was increased.
Participants in the control group were asked not to change their lifestyle over the 6 month duration of
the trial.
Outcomes Total simple Reaction time

Fractionated Reaction time (PreMotorTime and MotorTime)
Speed of Movement measurements
Fat percentage (predicted from body density)
Body density (7 skinfolds)
1RM muscle strength test
VO2 max
Notes Testing took place at the University of Florida College of Medicine.
Informed decisions.
Panton 1990 (Continued)

Aerobic capacity significantly improved by 20.4% (from 22.5 to 27.1 mL/kg/min) for subjects in the
walk/jog group; participants in both the strength as well as the control group showed no significant
changes in VO2 max (from 22.5 to 23.3 and 22.2 to 22.0, respectively).
Risk of bias


(selection bias)
Participants
Trainers
Blinding (performance Low risk Cognitive function was assessed by computer and therefore adequately blind-
bias and detection bias) ed.
Outcome assessors
Incomplete outcome data High risk 8/57 participants were lost to follow-up; it is unclear from which condition
(attrition bias) these participants were lost. Main outcomes were not analysed according to
All outcomes the ITT principle.

porting bias)
Whitehurst 1991
Methods Parallel-group RCT: 1 intervention group and 1 control group. 14 participants at randomisation (all fe-
males): 7 in both the exercise and the control group.
Follow-up: 8 weeks.
Participants Females in the age range of 61 to 73 years living in a rural community in North Carolina.
Inclusion criteria: did not participate in aerobic exercise more than one time per week prior to the trial.
Medical clearance from a physician (resting ECG and physical examination). Free of primary cardiovas-
cular risk factors. Maintained the household.
Interventions Exercise: 3 supervised sessions per week for 8 weeks (total of 24 sessions). 5 to 10 minutes of warming
up and cooling down. The participants cycled for 8 to 10 minutes the first week to provide acclimati-
zation. Thereafter, 3 to 5 minutes was added to subsequent sessions so that by week 4 all participants
were cycling for 35 to 40 minutes at their target heart rate.
Control: did not engage in any form of vigorous physical activity during the course of the trial.
Outcomes Simple reaction time

Choice reaction time
Informed decisions.
Whitehurst 1991 (Continued)

Estimated VO2 max
Notes Testing took place at the Human Performance Laboratory, Florida Atlantic University.
The subjects in the exercise group significantly increased their VO2 max values by an average 16%
(from 25.4 to 29.7 mL/kg/min), whereas the subjects in the control group increased their VO2 max by a
(non significant) 2% (from 24.7 to 25.4 mL/kg/min).
Risk of bias


(selection bias)
Participants
Trainers
Blinding (performance Low risk Cognitive function was assessed by computer (quote: "a standard choice reac-
bias and detection bias) tion-time apparatus was used") and therefore adequately blinded.
Outcome assessors
(attrition bias)
All outcomes

porting bias)
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Alessi 1999 No pre to post-intervention cognitive data. Mean MMSE scores of the participants was below the
range of what is considered 'normal' cognition (mean MMSE of 13.6 ± 8.5).
Alves 2012 No measure of cardiorespiratory fitness.
Barry 1966 Not a RCT but a CCT.
Blumenthal 1988 Participants were too young to meet the given inclusion criteria of this review.
Blumenthal 1991 Data were already published in Blumenthal 1989.
Bream 1996 No published data.
Informed decisions.
Carles 2007 Participants were too young to meet the given inclusion criteria of this review.
Cassilhas 2007 Exercise was not intended to improve aerobic fitness and no fitness parameters present.
Colcombe 2006 No pre to post-intervention cognitive data.
Deary 2006 Not a RCT but a longitudinal survey.
Dietrich 2004 Data could not test the cardiovascular fitness hypothesis since cognition was assessed during exer-
cise.
Dorner 2007 Participants had cognitive impairment; cognitive impairment was an exclusion criterium for our re-
view.
Dustman 1984 Not a RCT but a quasi-randomised study (participants "alternately assigned").
Emery 1990b Perceived (subjective) measurements of cognition were analysed according to groups but the ob-
jective measures of cognition were analysed according to perceived measures of cognition.
Emery 1998 Only had combined intervention groups and no pure aerobic exercise intervention group.
Emery 2003 Within participants repeated measures design to evaluate the influence of music and exercise on
cognition. No control group.
Erickson 2007 Not a RCT but a cross-sectional study.
Etnier 1997a No exercise intervention.
Etnier 2001 The control group was encouraged to continue exercising; however no formal programme was pro-
vided.
Fabre 1999 No means and SDs for cognitive data. These results are described in Fabre 2002.
Gates 2011 Selected participants that have early changes in memory without diagnosis and excluded people
with perfect MMSE.
Glisky 1997 No published data.
Hassmén 1992 Not RCT but "matched controls".
Hassmén 1997 Not a RCT, participants matched on cognitive performance in pairs, then randomised.
Hawkins 1992 No fitness parameter present.
Hill 1993 Not a RCT but a quasi-randomised study (participants "assigned to intervention group").
Ijuin 2013 No measure of aerobic fitness and not peer-reviewed.
Jacobson 2007 No fitness parameter present and not published in a peer reviewed journal.
Jedrziewski 2007 Not a RCT but a narrative review.
Kerschan 2002 Both groups followed aerobic training intervention.
Informed decisions.
Kharti 2001 Study participants were depressed older men and women: depression was an exclusion criterion
for our review.
Kramer 1999 This article provides no quantitative data on which an analysis can be based. Quantitative data of
the RCT of this research group is provided in Kramer 2001, which is included in our review.
Kramer 2007 Not a RCT but a narrative review.
Larson 2006 Not a RCT but a prospective cohort study.
Lautenschlager 2008 No assessment of fitness parameters.
Leinonen 2007 No pre- to post-intervention data present, only selected baseline results.
Littbrand 2006 No pre- to post-intervention cognitive data. Applicability study for the evaluation of attendance
and adverse events of an exercise programme.
Liu-Ambrose 2010 No measure of cardiorespiratory fitness.
Masley 2009 RCT included younger, middle-aged and older adults.
McAuley 2006 No pre- to post-intervention cognitive parameters.
McKenzie 2000 No published data.
Molloy 1988 Exercise was not intended to improve aerobic fitness.
Mortimer 2012 No aerobic fitness measure.
Munguía-Izquierdo 2007 Participants were too young to meet the given inclusion criteria of this review. No fitness parame-
ters present.
Netz 2007 Data could not test the cardiovascular fitness hypothesis since cognition was assessed during exer-
cise.
O'Dwyer 2007 Not a RCT but description of a study protocol.
Oken 2004 Participants were too young to meet the given inclusion criteria of this review.
Okumiya 1996 No fitness parameter present.
Palleschi 1996 Participants were elderly patients with senile dementia of the Alzheimer type: this was an exclusion
criterion for our review.
Palmer 1995 No published data.
Perri 1984 Not a true RCT but a clinical trial.
Pierce 1993 Participants were too young to meet the inclusion criteria of this review.
Plati 2006 Not a RCT but "matched controls".
Powell 1975 Narrative review; this article provides no quantitative data.
Powers 2007 No published data.
Informed decisions.
Predovan 2012 Not a RCT, group selection was based on order of recruitment and willingness to participate in an
exercise programme.
Prohaska 2007 Not a RCT but a narrative article.
Querry 1998 No published data.
Rikli 1991 Balance, sit and reach flexibility, shoulder flexibility, and grip strength were given as fitness para-
meters. We excluded this RCT since neither of the two fitness parameters reflect aerobic fitness.
Rosendahl 2006 No pre- to post-intervention cognitive data. Mean MMSE scores of the participants was below the
range of what is considered 'normal' cognition (mean MMSE of 17.8 ± 5.1).
Russell 1984 No published data.
Sato 2007 No cognition or fitness parameters, or both.
Shatil 2013 No objective measure of aerobic fitness in all groups.
Sibley 2007 Not a RCT and data could not test the cardiovascular fitness hypothesis since cognition was as-
sessed during exercise.
Small 2006 No fitness parameters present.
Smiley-Oyen 2008 Not a RCT but a quasi-randomised study ("Group allocation alternated between CARDIO and FLEX-
TONE").
Stevenson 1990 Both intervention groups received aerobic training (different levels of intensity).
van Uffelen 2007 Participants had mild cognitive impairment; cognitive impairment was an exclusion criterion for
our review.
Verghese 2006 Not a RCT but a prospective cohort study.
Wallman 2004 Participants were too young to meet the inclusion criteria of this review.
Wilbur 2005 No objective measures of cognitive parameters (symptom impact inventory).
Williams 1997 No objective measures of fitness, only subjective measures (Perceived General Fitness).
Williamson 2009 No assessment of fitness parameters. What could have been used to assess fitness (400 m walk)
was taken here as part of an assessment of functionality (specifically normal gait speed) and be-
cause of how this measure was implemented (walked at usual pace, allowed to rest, allowed to not
complete), it could not be used for fitness assessment.
Winter 2007 Data could not test the cardiovascular fitness hypothesis since cognition was assessed during exer-
cise.
Zlomanczuk 2006 No fitness parameters present.
Characteristics of studies awaiting assessment [ordered by study ID]
Informed decisions.
Chapman 2013
Methods Parallel-group, randomised, controlled trial: 1 intervention group, 1 wait-list control group. 37 par-
ticipants at randomisation; 18 (13 female) were put into the physical training group, 19 (14 female)
were put into the control group.
Follow-up: 12 weeks
Participants Participants were 57 to 75 years of age.
Inclusion criteria: "no prior history of neurological or psychiatric conditions, average IQ range, na-
tive English speaker, and minimum of a high school diploma"
Exclusion criteria: "MR scanning contraindications, cognitive impairment (TICS-M < 28 and MoCA <
26), elevated depressive symptoms (BDI >14), left-handedness, increased body mass BMI > 40, ab-
normal electrocardiographic response, significant hypertensive blood pressure response to exer-
cise, or inability to reach 85% of maximum predicted heart rate for age... if they reported regular
aerobic activity of more than twice a week for 20 min or more.They could not have regularly exer-
cised for at least 3 months prior to enrolling in the study."
Interventions Physical Training: "The training regimen consisted of three 60 min sessions of aerobic exercise
training per week for a period of 12 weeks. The participants’ aerobic exercise alternated each ses-
sion between exercise bike and treadmill. The exercise bike routine included: 5 min warm up at
43 watts, cycling for 50 min at a speed that increased their heart rate to 50–75% of their maximum
achieved heart rate on VO2 max testing, and a 5 min cool down at 43 watts. The treadmill workout
included: 5 min warmup at 2 miles per h (mph), walking on treadmill for 50 min at a speed that in-
creased their heart rate to 50–75% of their maximum achieved heart rate on VO2 max testing, and a
5 min cool down at 2mph."
Control: Wait-list
Outcomes Wechsler Abbreviated Scale of Intelligence (WASI)
BDI
MoCA
Tics-M
Trails B - Trails A
CVLT-II
WMS-IV immediate/delayed memory
Delis-Kaplan Executive Function System-Color Word Interference subtest (DKEFS- color word)
Backward Digit Span
BMI
Structural MRI
absolute Cerebral Blood Flow (aCBF)
RPE
VO2 max
Notes Testing took place at the The University of Texas at Dallas, The University of Texas Southwestern
Medical Center, and The Cooper Institute.
Informed decisions.
Chapman 2013 (Continued)

VO2 max increased significantly to a greater extent for the Physical Training group than the Control
group at the mid-point (p = .03), however at the endpoint change in VO2 max did not differ between
the groups.
Linde 2014
Methods Parallel-group, randomised, controlled trial: 3 intervention groups, 1 wait-list control group. 70 par-
ticipants were randomised: 19 (11 female) to a physical intervention group, 18 (9 female) to a cog-
nitive intervention group, 17 (11 female) to a combined physical and cognitive intervention group,
and 16 (10 female) to a wait-list control group.
Follow-ups: 16-weeks and 3 months after conclusion of intervention
Participants Participants were aged 60-75 from a "medium-sized German city"
Inclusion criteria: "age of 60–75 years"
Exclusion criteria: "dementia, depression, and possible medical conditions (e.g., coronary heart
diseases, hypertension, stroke, pulmonary diseases) that would not allow for participation in a reg-
ular exercise program."
Interventions "The interventions took place in groups of 8–10 participants and were hosted at the facilities of the
Faculty of Sport Sciences and its campus."
Physical Activity Intervention: "Participants trained two times per week, each session lasting 60
min, for a period of 16 weeks." Sessions consisted of 20 mins progressive strength training of each
major muscle group and 40 mins aerobic endurance training - 5 minute warm-up, 30 minute walk-
ing or running, 5 minute cool down. "Each individual was asked to exercise at an intensity of 40–
50% heart rate reserve (moderate intensity) during the beginner’s stage; the intensity of activity
was then incrementally increased to 60–70% (moderate to vigorous intensity) by the end of the de-
velopmental stage."
Cognitive Activity Intervention: "Cognitive training took place once a week for approximately 30
min... The primary element of the cognitive intervention consisted of the individual editing of
worksheets. In addition, some partner and group exercises were carried out. During the first 5 min,
warm-up exercises were performed as a group (e.g., training of short-term memory) or homework
was discussed. Some small amount of information was then given relating to one of the following
topics: information processing speed, attention, introduction to the memory model, sensory mem-
ory, short-term memory, mnemonics, long-term memory, and memory aids. Following the distribu-
tion of information, the following cognitive abilities were practiced for 25 min: short-term memory,
visuospatial skills, information processing speed, concentration, and logical reasoning. At the end
of each session two additional exercises were provided as homework."
Combined Physical and Cognitive Activity Intervention: "The combined intervention consisted of
the physical plus cognitive interventions and took place twice a week. The cognitive training pro-
gram was carried out at the first training session of the week, before the physical training. The total
duration of the first training session each week therefore was 90 min, while the second session last-
ed only 60 min (consisting only of physical training)."
Wait-list Control: "An inactive waiting control group was selected to act as a comparison group.
Study participants in the control group were asked to continue their daily routines as before. To in-
crease the motivation to participate in the study, a 12-week fitness class was offered after the fol-
low-up assessment."
Outcomes Reasoning subtest of Leistungs-Prüf-System 50+ (LPS 50+)
Spatial relations subtest of LPS 50+
d2: Test of Attention
Informed decisions.
Linde 2014 (Continued)

Trail Making Test Part A
Digit-Symbol Substitution Test (DSST from NAI)
Word List test (NAI subtest)
2-km walking test to estimate VO2 max
Notes Testing was conducted at the Faculty of Sport Science at the University of Leipzig.
Increase of cardiovascular fitness were not significantly different between the control and interven-
tion groups.
DATA AND ANALYSES
Comparison 1. Aerobic exercise versus any active intervention
Outcome or subgroup title No. of No. of Statistical method Effect size

studies partici-
pants
1 Cognitive speed 6 389 Std. Mean Difference (IV, Random, 0.12 [-0.08, 0.33]
95% CI)
1.1 Simple reaction time 2 113 Std. Mean Difference (IV, Random, 0.09 [-0.28, 0.46]
95% CI)
1.2 Choice reaction time 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
1.3 Trailmaking part A 1 49 Std. Mean Difference (IV, Random, -0.36 [-0.96, 0.24]
95% CI)
1.4 Digit symbol substitution 3 227 Std. Mean Difference (IV, Random, 0.24 [-0.03, 0.50]
95% CI)
2 Verbal memory functions (immediate) 5 292 Std. Mean Difference (IV, Random, 0.08 [-0.38, 0.55]
95% CI)
2.1 16 words immediate recall 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
2.2 Randt Memory test story recall 1 65 Std. Mean Difference (IV, Random, 0.34 [-0.15, 0.83]
95% CI)
2.3 Ross Information Processing Assess- 1 30 Std. Mean Difference (IV, Random, 0.60 [-0.18, 1.37]
ment immediate memory 95% CI)
2.4 Wechsler Adult Intelligence Scales log- 1 24 Std. Mean Difference (IV, Random, -1.41 [-2.36, -0.45]
ical memory immediate recall 95% CI)
2.5 Rey auditory verbal learning trial I-V 1 124 Std. Mean Difference (IV, Random, 0.10 [-0.25, 0.45]
95% CI)
Informed decisions.

studies partici-
pants
2.6 Hopkins Verbal Learning Test (imme- 1 49 Std. Mean Difference (IV, Random, 0.34 [-0.27, 0.94]
diate) 95% CI)
3 Visual memory functions (immediate) 2 89 Std. Mean Difference (IV, Random, -0.26 [-0.97, 0.44]
95% CI)
3.1 Benton visual retention (#error) 1 65 Std. Mean Difference (IV, Random, 0.02 [-0.47, 0.50]
95% CI)
3.2 Wechsler Memory Scales visual repro- 1 24 Std. Mean Difference (IV, Random, -0.73 [-1.61, 0.15]
duction 95% CI)
4 Working memory 3 238 Std. Mean Difference (IV, Random, 0.10 [-0.16, 0.36]
95% CI)
4.1 Digit span backward 2 189 Std. Mean Difference (IV, Random, 0.16 [-0.13, 0.45]
95% CI)
4.2 2-Back (accuracy, Hits - False Alarms) 1 49 Std. Mean Difference (IV, Random, -0.14 [-0.74, 0.46]
95% CI)
5 Memory functions (delayed) 3 249 Std. Mean Difference (IV, Random, 0.10 [-0.16, 0.35]
95% CI)
5.1 16 words delayed recall 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
5.2 Rey auditory verbal learning delayed 1 124 Std. Mean Difference (IV, Random, 0.19 [-0.17, 0.54]
recall trial 95% CI)
5.3 10 words delayed recall 1 76 Std. Mean Difference (IV, Random, -0.10 [-0.55, 0.35]
95% CI)
5.4 Hopkins Verbal Learning Test - 12 1 49 Std. Mean Difference (IV, Random, 0.18 [-0.42, 0.78]
words (delayed) 95% CI)
6 Executive functions 6 367 Std. Mean Difference (IV, Random, 0.38 [-0.14, 0.90]
95% CI)
6.1 Trailmaking part B 2 113 Std. Mean Difference (IV, Random, 0.27 [-0.11, 0.65]
95% CI)
6.2 Ross Information Processing Assess- 1 30 Std. Mean Difference (IV, Random, 2.75 [1.69, 3.82]
ment problem solving and abstract rea- 95% CI)
soning
6.3 Wechsler Memory Scales mental con- 1 24 Std. Mean Difference (IV, Random, -0.31 [-1.16, 0.55]
trol 95% CI)
6.4 Task switching paradigm (accuracy) 1 124 Std. Mean Difference (IV, Random, 0.03 [-0.32, 0.38]
95% CI)
6.5 Verbal fluency 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
Informed decisions.

studies partici-
pants
6.6 Letter number sequencing 1 76 Std. Mean Difference (IV, Random, 0.07 [-0.38, 0.52]
95% CI)
7 Perception 3 178 Std. Mean Difference (IV, Random, -0.01 [-0.50, 0.48]
95% CI)
7.1 Face recognition (delayed recall) 1 124 Std. Mean Difference (IV, Random, 0.17 [-0.18, 0.53]
95% CI)
ment auditory processing 95% CI)
7.3 Wechsler Adult Intelligence Scales vi- 1 24 Std. Mean Difference (IV, Random, -0.73 [-1.61, 0.15]
sual reproduction 95% CI)
8 Cognitive inhibition 4 314 Std. Mean Difference (IV, Random, -0.06 [-0.28, 0.17]
95% CI)
8.1 Stroop colour word (interference) 2 141 Std. Mean Difference (IV, Random, -0.13 [-0.46, 0.20]
95% CI)
8.2 Stopping task (accuracy choice RT) 1 124 Std. Mean Difference (IV, Random, 0.01 [-0.35, 0.36]
95% CI)
8.3 Flanker Task (Incongruent RT) 1 49 Std. Mean Difference (IV, Random, 0.00 [-0.59, 0.60]
95% CI)
9 Visual attention 3 265 Std. Mean Difference (IV, Random, 0.22 [-0.03, 0.46]
95% CI)
9.1 Digit vigilance 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
9.2 Tracking (accuracy index) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
9.3 2&7 test 1 65 Std. Mean Difference (IV, Random, 0.30 [-0.19, 0.79]
95% CI)
9.4 Visual search (accuracy) 1 124 Std. Mean Difference (IV, Random, 0.25 [-0.10, 0.60]
95% CI)
9.5 Covert orienting of visuospatial atten- 1 76 Std. Mean Difference (IV, Random, 0.09 [-0.36, 0.54]
tion 95% CI)
10 Auditory attention 4 251 Mean Difference (IV, Random, 95% 0.15 [-0.38, 0.69]
CI)
10.1 Digit span forward 4 251 Mean Difference (IV, Random, 95% 0.15 [-0.38, 0.69]
CI)
11 Motor function 2 189 Std. Mean Difference (IV, Random, 0.08 [-0.20, 0.37]
95% CI)
Informed decisions.

studies partici-
pants
11.1 Finger tapping 1 65 Std. Mean Difference (IV, Random, 0.19 [-0.30, 0.68]
95% CI)
11.2 Pursuit rotor task (tracking error) 1 124 Std. Mean Difference (IV, Random, 0.02 [-0.33, 0.38]
95% CI)
12 Drop-out 7 469 Odds Ratio (M-H, Random, 95% CI) 0.96 [0.44, 2.10]
Analysis 1.1. Comparison 1 Aerobic exercise versus any active intervention, Outcome 1 Cognitive speed.
Study or subgroup Treatment Control Std. Mean Difference Weight Std. Mean Difference
N Mean(SD) N Mean(SD) Random, 95% CI Random, 95% CI
1.1.1 Simple reaction time
Oken 2006 38 -321.9 38 -335.6 (74) 20.1% 0.18[-0.27,0.63]
(79.7)
Panton 1990 17 -274 (28.9) 20 -270 (44.7) 9.75% -0.1[-0.75,0.54]
Subtotal *** 55 58 29.85% 0.09[-0.28,0.46]
Heterogeneity: Tau2=0; Chi2=0.48, df=1(P=0.49); I2=0%
Test for overall effect: Z=0.45(P=0.65)
1.1.2 Choice reaction time

Subtotal *** 0 0 Not estimable
Heterogeneity: Not applicable
Test for overall effect: Not applicable
1.1.3 Trailmaking part A

Legault 2011 16 -37.4 (11.3) 33 -34.2 (7.2) 11.27% -0.36[-0.96,0.24]
Subtotal *** 16 33 11.27% -0.36[-0.96,0.24]
1.1.4 Digit symbol substitution

Blumenthal 1989 31 52.5 (8.6) 34 48.7 (10) 16.86% 0.4[-0.09,0.9]
Emery 1990a 14 35.8 (12.6) 24 32.9 (11.3) 9.32% 0.24[-0.42,0.9]
Kramer 2001 58 96.5 (3.9) 66 95.7 (6.3) 32.7% 0.15[-0.2,0.5]
Subtotal *** 103 124 58.88% 0.24[-0.03,0.5]
Total *** 174 215 100% 0.12[-0.08,0.33]

Test for subgroup differences: Chi2=3.24, df=1 (P=0.2), I2=38.35%
Favours control -4 -2 0 2 4 Favours aerobic
Informed decisions.
Analysis 1.2. Comparison 1 Aerobic exercise versus any active

intervention, Outcome 2 Verbal memory functions (immediate).
1.2.1 16 words immediate recall
1.2.2 Randt Memory test story recall

Blumenthal 1989 31 11.1 (3.9) 34 9.8 (3.5) 23.11% 0.34[-0.15,0.83]
Subtotal *** 31 34 23.11% 0.34[-0.15,0.83]
1.2.3 Ross Information Processing Assessment immediate memory

Moul 1995 10 23.5 (3.5) 20 19.6 (7.3) 16.62% 0.6[-0.18,1.37]
Subtotal *** 10 20 16.62% 0.6[-0.18,1.37]
1.2.4 Wechsler Adult Intelligence Scales logical memory immediate recall

Fabre 2002 8 7.4 (1) 16 9.1 (1.2) 13.42% -1.41[-2.36,-0.45]
Subtotal *** 8 16 13.42% -1.41[-2.36,-0.45]
Test for overall effect: Z=2.89(P=0)
1.2.5 Rey auditory verbal learning trial I-V

Kramer 2001 58 10 (1.8) 66 9.8 (2.1) 26.41% 0.1[-0.25,0.45]
Subtotal *** 58 66 26.41% 0.1[-0.25,0.45]
1.2.6 Hopkins Verbal Learning Test (immediate)

Legault 2011 16 6.4 (1.8) 33 5.8 (1.6) 20.44% 0.34[-0.27,0.94]
Subtotal *** 16 33 20.44% 0.34[-0.27,0.94]
Total *** 123 169 100% 0.08[-0.38,0.55]

Heterogeneity: Tau2=0.18; Chi2=12.53, df=4(P=0.01); I2=68.08%
Analysis 1.3. Comparison 1 Aerobic exercise versus any active

intervention, Outcome 3 Visual memory functions (immediate).
1.3.1 Benton visual retention (#error)
Informed decisions.
Blumenthal 1989 31 -5.5 (3.3) 34 -5.6 (3.7) 62.61% 0.02[-0.47,0.5]
Subtotal *** 31 34 62.61% 0.02[-0.47,0.5]
Heterogeneity: Tau2=0; Chi2=0, df=0(P<0.0001); I2=100%
1.3.2 Wechsler Memory Scales visual reproduction

Fabre 2002 8 10.2 (2.8) 16 11.7 (1.3) 37.39% -0.73[-1.61,0.15]
Subtotal *** 8 16 37.39% -0.73[-1.61,0.15]
Total *** 39 50 100% -0.26[-0.97,0.44]

Analysis 1.4. Comparison 1 Aerobic exercise versus any active intervention, Outcome 4 Working memory.
1.4.1 Digit span backward
Blumenthal 1989 31 7.9 (2.9) 34 6.9 (2.3) 27.69% 0.37[-0.12,0.86]
Kramer 2001 58 7.2 (1.8) 66 7.1 (2.1) 53.63% 0.05[-0.3,0.4]
Subtotal *** 89 100 81.32% 0.16[-0.13,0.45]
Heterogeneity: Tau2=0; Chi2=1.05, df=1(P=0.31); I2=4.67%
1.4.2 2-Back (accuracy, Hits - False Alarms)

Legault 2011 16 0.6 (0.2) 33 0.6 (0.2) 18.68% -0.14[-0.74,0.46]
Subtotal *** 16 33 18.68% -0.14[-0.74,0.46]
Total *** 105 133 100% 0.1[-0.16,0.36]

Test for subgroup differences: Chi2=0.77, df=1 (P=0.38), I2=0%
Analysis 1.5. Comparison 1 Aerobic exercise versus any

active intervention, Outcome 5 Memory functions (delayed).
1.5.1 16 words delayed recall
Informed decisions.
1.5.2 Rey auditory verbal learning delayed recall trial

Kramer 2001 58 11.4 (2.7) 66 10.9 (2.6) 50.85% 0.19[-0.17,0.54]
Subtotal *** 58 66 50.85% 0.19[-0.17,0.54]

Oken 2006 38 7 (2) 38 7.2 (1.9) 31.39% -0.1[-0.55,0.35]
Subtotal *** 38 38 31.39% -0.1[-0.55,0.35]
1.5.4 Hopkins Verbal Learning Test - 12 words (delayed)

Legault 2011 16 9.4 (2.2) 33 8.9 (2.5) 17.76% 0.18[-0.42,0.78]
Subtotal *** 16 33 17.76% 0.18[-0.42,0.78]
Total *** 112 137 100% 0.1[-0.16,0.35]

Analysis 1.6. Comparison 1 Aerobic exercise versus any active intervention, Outcome 6 Executive functions.
1.6.1 Trailmaking part B
Blumenthal 1989 31 -79.5 (27.6) 34 -90.9 (34) 18.54% 0.36[-0.13,0.85]
Legault 2011 15 -81.5 (49.1) 33 -86.2 (28.5) 16.98% 0.13[-0.48,0.74]
Subtotal *** 46 67 35.51% 0.27[-0.11,0.65]
1.6.2 Ross Information Processing Assessment problem solving and abstract

reasoning
Moul 1995 10 27.3 (3.5) 20 18.5 (2.9) 11.43% 2.75[1.69,3.82]
Subtotal *** 10 20 11.43% 2.75[1.69,3.82]
Test for overall effect: Z=5.06(P<0.0001)
1.6.3 Wechsler Memory Scales mental control

Fabre 2002 8 5.9 (0.9) 16 6.2 (1) 13.84% -0.31[-1.16,0.55]
Subtotal *** 8 16 13.84% -0.31[-1.16,0.55]
Informed decisions.
1.6.4 Task switching paradigm (accuracy)

Kramer 2001 58 95.8 (6.3) 66 95.6 (7.4) 20.17% 0.03[-0.32,0.38]
Subtotal *** 58 66 20.17% 0.03[-0.32,0.38]
1.6.5 Verbal fluency

1.6.6 Letter number sequencing

Oken 2006 38 10.7 (2.8) 38 10.5 (2.6) 19.05% 0.07[-0.38,0.52]
Subtotal *** 38 38 19.05% 0.07[-0.38,0.52]
Total *** 160 207 100% 0.38[-0.14,0.9]

Heterogeneity: Tau2=0.31; Chi2=25.1, df=5(P=0); I2=80.08%
Test for subgroup differences: Chi2=24.76, df=1 (P<0.0001), I2=83.84%
Analysis 1.7. Comparison 1 Aerobic exercise versus any active intervention, Outcome 7 Perception.
1.7.1 Face recognition (delayed recall)
Kramer 2001 58 75.1 (18.3) 66 71.4 (23.6) 52.02% 0.17[-0.18,0.53]
Subtotal *** 58 66 52.02% 0.17[-0.18,0.53]
1.7.2 Ross Information Processing Assessment auditory processing

Moul 1995 10 27.7 (3.8) 20 27.1 (2.1) 26.25% 0.21[-0.55,0.97]
Subtotal *** 10 20 26.25% 0.21[-0.55,0.97]
1.7.3 Wechsler Adult Intelligence Scales visual reproduction

Fabre 2002 8 10.2 (2.8) 16 11.7 (1.3) 21.72% -0.73[-1.61,0.15]
Subtotal *** 8 16 21.72% -0.73[-1.61,0.15]
Total *** 76 102 100% -0.01[-0.5,0.48]

Informed decisions.
Analysis 1.8. Comparison 1 Aerobic exercise versus any active intervention, Outcome 8 Cognitive inhibition.
1.8.1 Stroop colour word (interference)
Blumenthal 1989 31 -1.7 (6.3) 34 -1.2 (6.1) 21.11% -0.07[-0.55,0.42]
Oken 2006 38 -10.8 (4.3) 38 -10 (4.6) 24.65% -0.18[-0.63,0.27]
Subtotal *** 69 72 45.75% -0.13[-0.46,0.2]
1.8.2 Stopping task (accuracy choice RT)

Kramer 2001 58 93.1 (132.5) 66 92.3 (150.3) 40.21% 0.01[-0.35,0.36]
Subtotal *** 58 66 40.21% 0.01[-0.35,0.36]
1.8.3 Flanker Task (Incongruent RT)

Legault 2011 16 -538.8 33 -539.1 14.04% 0[-0.59,0.6]
(67.9) (80.5)
Subtotal *** 16 33 14.04% 0[-0.59,0.6]
Total *** 143 171 100% -0.06[-0.28,0.17]

Analysis 1.9. Comparison 1 Aerobic exercise versus any active intervention, Outcome 9 Visual attention.
1.9.1 Digit vigilance
1.9.2 Tracking (accuracy index)

Informed decisions.
1.9.3 2&7 test

Blumenthal 1989 31 -6.8 (5.1) 34 -9.1 (9.3) 24.41% 0.3[-0.19,0.79]
Subtotal *** 31 34 24.41% 0.3[-0.19,0.79]
1.9.4 Visual search (accuracy)

Kramer 2001 58 97.8 (3.3) 66 97 (3) 46.66% 0.25[-0.1,0.6]
Subtotal *** 58 66 46.66% 0.25[-0.1,0.6]
1.9.5 Covert orienting of visuospatial attention

Oken 2006 38 -37.1 (34.1) 38 -40.3 (36.8) 28.92% 0.09[-0.36,0.54]
Subtotal *** 38 38 28.92% 0.09[-0.36,0.54]
Total *** 127 138 100% 0.22[-0.03,0.46]

Analysis 1.10. Comparison 1 Aerobic exercise versus any active intervention, Outcome 10 Auditory attention.
Study or subgroup Treatment Control Mean Difference Weight Mean Difference
1.10.1 Digit span forward
Blumenthal 1989 31 8.9 (2.6) 34 8.6 (2) 18.07% 0.33[-0.81,1.46]
Emery 1990a 14 11.5 (4.3) 24 11.4 (4.2) 3.45% 0.1[-2.71,2.91]
Fabre 2002 8 6.1 (0.7) 16 5.6 (0.8) 42.7% 0.55[-0.08,1.18]
Kramer 2001 58 8 (2) 66 8.4 (2.1) 35.78% -0.4[-1.12,0.32]
Subtotal *** 111 140 100% 0.15[-0.38,0.69]
Total *** 111 140 100% 0.15[-0.38,0.69]

Informed decisions.
Analysis 1.11. Comparison 1 Aerobic exercise versus any active intervention, Outcome 11 Motor function.
1.11.1 Finger tapping
Blumenthal 1989 31 123.6 (14.3) 34 120.4 (18.8) 34.33% 0.19[-0.3,0.68]
Subtotal *** 31 34 34.33% 0.19[-0.3,0.68]
1.11.2 Pursuit rotor task (tracking error)

Kramer 2001 58 -29.6 (6.3) 66 -29.8 (6.6) 65.67% 0.02[-0.33,0.38]
Subtotal *** 58 66 65.67% 0.02[-0.33,0.38]
Total *** 89 100 100% 0.08[-0.2,0.37]

Analysis 1.12. Comparison 1 Aerobic exercise versus any active intervention, Outcome 12 Drop-out.
Study or subgroup Treatment Control Odds Ratio Weight Odds Ratio
n/N n/N M-H, Random, 95% CI M-H, Random, 95% CI
Blumenthal 1989 2/33 2/33 12.14% 1[0.13,7.55]
Emery 1990a 1/15 4/15 9.59% 0.2[0.02,2.02]
Fabre 2002 0/8 0/16 Not estimable
Kramer 2001 25/83 25/91 44.57% 1.14[0.59,2.2]
Legault 2011 3/18 0/36 6.06% 16.48[0.8,338.51]
Moul 1995 0/10 0/20 Not estimable
Oken 2006 6/44 9/47 27.65% 0.67[0.22,2.06]
Total (95% CI) 211 258 100% 0.96[0.44,2.1]

Total events: 37 (Treatment), 40 (Control)
Favours aerobic 0.01 0.1 1 10 100 Favours control
Comparison 2. Aerobic exercise versus no intervention

studies partici-
pants
95% CI)
1.1 Simple reaction time 2 109 Std. Mean Difference (IV, Random, -0.09 [-0.47, 0.29]
95% CI)
Informed decisions.

studies partici-
pants
1.2 Choice reaction time 1 14 Std. Mean Difference (IV, Random, -0.53 [-1.60, 0.54]
95% CI)
1.3 Trailmaking part A 1 72 Std. Mean Difference (IV, Random, 0.31 [-0.15, 0.78]
95% CI)
95% CI)
95% CI)
2.1 Randt Memory test story recall 1 65 Std. Mean Difference (IV, Random, -0.04 [-0.53, 0.45]
95% CI)
95% CI)
2.4 Wechsler Adult Intelligence Scales log- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
2.6 Hopkins Verbal Learning Test (imme- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
diate) 95% CI)
3 Visual memory functions (immediate) 1 65 Std. Mean Difference (IV, Random, -0.09 [-0.57, 0.40]
95% CI)
3.1 Benton visual retention (#error) 1 65 Std. Mean Difference (IV, Random, -0.09 [-0.57, 0.40]
95% CI)
3.2 Wechsler Memory Scales visual repro- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
duction 95% CI)
4 Working memory 2 137 Mean Difference (IV, Random, 95% CI) 0.30 [-0.54, 1.15]
4.1 Digit span backward 2 137 Mean Difference (IV, Random, 95% CI) 0.30 [-0.54, 1.15]
4.2 2-Back (accuracy, Hits - False Alarms) 0 0 Mean Difference (IV, Random, 95% CI) 0.0 [0.0, 0.0]
5 Memory functions (delayed) 2 152 Std. Mean Difference (IV, Fixed, 95% 0.09 [-0.23, 0.41]
CI)
5.1 16 words delayed recall 0 0 Std. Mean Difference (IV, Fixed, 95% 0.0 [0.0, 0.0]
CI)
5.2 Rey auditory verbal learning delayed 1 72 Std. Mean Difference (IV, Fixed, 95% 0.25 [-0.21, 0.72]
recall trial CI)
Informed decisions.

studies partici-
pants
5.3 10 words delayed recall 1 80 Std. Mean Difference (IV, Fixed, 95% -0.05 [-0.49, 0.38]
CI)
5.4 Hopkins Verbal Learning Test - 12 0 0 Std. Mean Difference (IV, Fixed, 95% 0.0 [0.0, 0.0]
words (delayed) CI)
95% CI)
95% CI)
soning
6.3 Wechsler Memory Scales mental con- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
trol 95% CI)
6.4 Task switching paradigm (accuracy) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
6.6 Letter number sequencing 1 80 Std. Mean Difference (IV, Random, -0.03 [-0.47, 0.41]
95% CI)
7 Cognitive inhibition 3 217 Std. Mean Difference (IV, Random, 0.20 [-0.06, 0.47]
95% CI)
7.1 Stroop colour word (interference) 3 217 Std. Mean Difference (IV, Random, 0.20 [-0.06, 0.47]
95% CI)
7.2 Stopping task (accuracy choice RT) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
7.3 Flanker Task (Incongruent RT) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
95% CI)
8.2 Tracking (accuracy index) 1 10 Std. Mean Difference (IV, Random, 0.76 [-0.55, 2.07]
95% CI)
95% CI)
8.4 Visual search (accuracy) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
Informed decisions.

studies partici-
pants
8.5 Covert orienting of visuospatial atten- 1 80 Std. Mean Difference (IV, Random, -0.02 [-0.45, 0.42]
tion 95% CI)
9 Auditory attention 1 65 Mean Difference (IV, Fixed, 95% CI) 0.16 [-1.01, 1.33]
9.1 Digit span forward 1 65 Mean Difference (IV, Fixed, 95% CI) 0.16 [-1.01, 1.33]
10 Motor function 1 65 Mean Difference (IV, Fixed, 95% CI) 0.10 [-7.87, 8.08]
10.1 Finger tapping 1 65 Mean Difference (IV, Fixed, 95% CI) 0.10 [-7.87, 8.08]
10.2 Pursuit rotor task (tracking error) 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
11 Drop-out 5 267 Odds Ratio (IV, Random, 95% CI) 1.84 [0.79, 4.29]
Analysis 2.1. Comparison 2 Aerobic exercise versus no intervention, Outcome 1 Cognitive speed.
Oken 2006 38 -321.9 42 -311.4 29.13% -0.13[-0.57,0.31]
(79.7) (78.5)
Panton 1990 17 -274 (28.9) 12 -275 (52) 12.8% 0.02[-0.71,0.76]
Subtotal *** 55 54 41.93% -0.09[-0.47,0.29]

Whitehurst 1991 7 -0.4 (0) 7 -0.4 (0) 6.53% -0.53[-1.6,0.54]
Subtotal *** 7 7 6.53% -0.53[-1.6,0.54]

Langlois 2012 36 -44.1 (13.4) 36 -49.5 (20.2) 26.88% 0.31[-0.15,0.78]
Subtotal *** 36 36 26.88% 0.31[-0.15,0.78]

Blumenthal 1989 31 52.5 (9) 34 48.2 (10.2) 24.66% 0.44[-0.05,0.94]
Subtotal *** 31 34 24.66% 0.44[-0.05,0.94]
Total *** 129 131 100% 0.12[-0.16,0.41]

Informed decisions.
Analysis 2.2. Comparison 2 Aerobic exercise versus no

intervention, Outcome 2 Verbal memory functions (immediate).
Blumenthal 1989 31 11.1 (3.9) 34 11.2 (3.8) 47.53% -0.04[-0.53,0.45]
Subtotal *** 31 34 47.53% -0.04[-0.53,0.45]




Langlois 2012 36 10.9 (3.1) 36 10.2 (3.8) 52.47% 0.21[-0.25,0.67]
Subtotal *** 36 36 52.47% 0.21[-0.25,0.67]

Total *** 67 70 100% 0.09[-0.24,0.43]

Informed decisions.
Analysis 2.3. Comparison 2 Aerobic exercise versus no

intervention, Outcome 3 Visual memory functions (immediate).
Blumenthal 1989 31 -5.5 (3.3) 34 -5.3 (3.2) 100% -0.09[-0.57,0.4]
Subtotal *** 31 34 100% -0.09[-0.57,0.4]

Total *** 31 34 100% -0.09[-0.57,0.4]

Test for subgroup differences: Not applicable
Analysis 2.4. Comparison 2 Aerobic exercise versus no intervention, Outcome 4 Working memory.
Blumenthal 1989 31 7.8 (2.9) 34 7.3 (2.2) 45.38% 0.46[-0.78,1.71]
Langlois 2012 36 6.6 (2.5) 36 6.5 (2.5) 54.62% 0.17[-0.97,1.31]
Subtotal *** 67 70 100% 0.3[-0.54,1.15]

Total *** 67 70 100% 0.3[-0.54,1.15]

Analysis 2.5. Comparison 2 Aerobic exercise versus no intervention, Outcome 5 Memory functions (delayed).
N Mean(SD) N Mean(SD) Fixed, 95% CI Fixed, 95% CI
Informed decisions.

Langlois 2012 36 10.6 (3.2) 36 9.6 (4) 47.23% 0.25[-0.21,0.72]
Subtotal *** 36 36 47.23% 0.25[-0.21,0.72]

Oken 2006 38 7 (2) 42 7.1 (1.6) 52.77% -0.05[-0.49,0.38]
Subtotal *** 38 42 52.77% -0.05[-0.49,0.38]

Total *** 74 78 100% 0.09[-0.23,0.41]

Analysis 2.6. Comparison 2 Aerobic exercise versus no intervention, Outcome 6 Executive functions.
Blumenthal 1989 31 -79.5 (27.6) 34 -81.5 (36.3) 31.45% 0.06[-0.43,0.55]
Langlois 2012 36 -104.9 36 -136.2 32.83% 0.53[0.06,1]
(37.9) (72.9)
Subtotal *** 67 70 64.28% 0.3[-0.16,0.76]

reasoning

Informed decisions.


Oken 2006 38 10.7 (2.8) 42 10.8 (4) 35.72% -0.03[-0.47,0.41]
Subtotal *** 38 42 35.72% -0.03[-0.47,0.41]
Total *** 105 112 100% 0.18[-0.16,0.53]

Analysis 2.7. Comparison 2 Aerobic exercise versus no intervention, Outcome 7 Cognitive inhibition.
Blumenthal 1989 31 -1.7 (6.3) 34 -4.5 (6.7) 29.46% 0.44[-0.06,0.93]
Langlois 2012 36 -141.7 36 -149.4 (43) 33.4% 0.17[-0.29,0.63]
(46.5)
Oken 2006 38 -10.8 (4.3) 42 -11 (3.7) 37.14% 0.05[-0.39,0.49]
Subtotal *** 105 112 100% 0.2[-0.06,0.47]


Total *** 105 112 100% 0.2[-0.06,0.47]

Informed decisions.
Analysis 2.8. Comparison 2 Aerobic exercise versus no intervention, Outcome 8 Visual attention.

Bakken 2001 5 10.1 (23.4) 5 -16.2 (37.3) 5.81% 0.76[-0.55,2.07]
Subtotal *** 5 5 5.81% 0.76[-0.55,2.07]
2.8.3 2&7 test

Blumenthal 1989 31 6.8 (5.1) 34 6.6 (5) 42.23% 0.04[-0.44,0.53]
Subtotal *** 31 34 42.23% 0.04[-0.44,0.53]


Oken 2006 38 -37.1 (34.1) 42 -36.6 (30) 51.96% -0.02[-0.45,0.42]
Subtotal *** 38 42 51.96% -0.02[-0.45,0.42]
Total *** 74 81 100% 0.05[-0.26,0.37]

Analysis 2.9. Comparison 2 Aerobic exercise versus no intervention, Outcome 9 Auditory attention.
Blumenthal 1989 31 8.9 (2.6) 34 8.8 (2.2) 100% 0.16[-1.01,1.33]
Subtotal *** 31 34 100% 0.16[-1.01,1.33]
Total *** 31 34 100% 0.16[-1.01,1.33]

Informed decisions.

Analysis 2.10. Comparison 2 Aerobic exercise versus no intervention, Outcome 10 Motor function.
Blumenthal 1989 31 123.6 (14.3) 34 123.5 (18.4) 100% 0.1[-7.87,8.08]
Subtotal *** 31 34 100% 0.1[-7.87,8.08]

Total *** 31 34 100% 0.1[-7.87,8.08]

Analysis 2.11. Comparison 2 Aerobic exercise versus no intervention, Outcome 11 Drop-out.

n/N n/N IV, Random, 95% CI IV, Random, 95% CI
Bakken 2001 3/8 2/7 15.08% 1.5[0.17,13.23]
Blumenthal 1989 2/33 2/34 17.49% 1.03[0.14,7.79]
Langlois 2012 7/43 4/40 41.48% 1.75[0.47,6.5]
Oken 2006 6/44 2/44 25.95% 3.32[0.63,17.43]
Whitehurst 1991 0/7 0/7 Not estimable
Total (95% CI) 135 132 100% 1.84[0.79,4.29]

Informed decisions.
Comparison 3. Aerobic exercise versus flexibility/balance programme

studies partici-
pants
95% CI)
95% CI)
95% CI)
1.3 Trailmaking part A 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
3 Visual memory functions (immediate) 1 65 Mean Difference (IV, Fixed, 95% CI) 0.05 [-1.65, 1.76]
3.1 Benton visual retention (#error) 1 65 Mean Difference (IV, Fixed, 95% CI) 0.05 [-1.65, 1.76]
3.2 Wechsler Memory Scales visual repro- 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
duction
4 Working memory 2 189 Mean Difference (IV, Random, 95% CI) 0.36 [-0.41, 1.12]
4.1 Digit span backward 2 189 Mean Difference (IV, Random, 95% CI) 0.36 [-0.41, 1.12]
5 Memory functions (delayed) 2 200 Std. Mean Difference (IV, Random, 0.08 [-0.20, 0.36]
95% CI)
5.1 16 words delayed recall 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
5.2 Rey auditory verbal learning delayed 1 124 Std. Mean Difference (IV, Random, 0.19 [-0.17, 0.54]
recall trial 95% CI)
Informed decisions.

studies partici-
pants
5.3 10 words delayed recall 1 76 Std. Mean Difference (IV, Random, -0.10 [-0.55, 0.35]
95% CI)
95% CI)
95% CI)
soning
trol 95% CI)
95% CI)
95% CI)
6.6 Letter number sequencing 1 76 Std. Mean Difference (IV, Random, 0.07 [-0.38, 0.52]
95% CI)
7 Perception 2 144 Std. Mean Difference (IV, Random, 0.22 [-0.11, 0.54]
95% CI)
95% CI)
7.3 Wechsler Adult Intelligence Scales vi- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
Informed decisions.

studies partici-
pants
95% CI)
95% CI)
9.5 Covert orienting of visuospatial atten- 1 76 Std. Mean Difference (IV, Random, 0.09 [-0.36, 0.54]
tion 95% CI)
10 Auditory attention 2 189 Mean Difference (IV, Random, 95% CI) -0.17 [-0.83, 0.49]
10.1 Digit span forward 2 189 Mean Difference (IV, Random, 95% CI) -0.17 [-0.83, 0.49]
95% CI)
95% CI)
95% CI)
Analysis 3.1. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 1 Cognitive speed.
Oken 2006 38 -321.9 38 -335.6 (74) 28.87% 0.18[-0.27,0.63]
(79.7)
Subtotal *** 38 38 28.87% 0.18[-0.27,0.63]



Blumenthal 1989 31 52.5 (8.6) 34 48.7 (10) 24.21% 0.4[-0.09,0.9]
Kramer 2001 58 96.6 (3.9) 66 95.7 (6.3) 46.92% 0.17[-0.19,0.52]
Subtotal *** 89 100 71.13% 0.25[-0.04,0.54]
Favours control -4 -2 0 2 4 Favours treatment
Informed decisions.
Total *** 127 138 100% 0.23[-0.01,0.47]

Analysis 3.2. Comparison 3 Aerobic exercise versus flexibility/

balance programme, Outcome 2 Verbal memory functions (immediate).
Blumenthal 1989 31 11.1 (3.9) 34 9.8 (3.5) 36.83% 0.34[-0.15,0.83]
Subtotal *** 31 34 36.83% 0.34[-0.15,0.83]


Moul 1995 10 23.5 (3.5) 10 16 (8.2) 16.24% 1.14[0.18,2.1]
Subtotal *** 10 10 16.24% 1.14[0.18,2.1]


Kramer 2001 58 10 (1.8) 66 9.8 (2.1) 46.93% 0.1[-0.25,0.45]
Subtotal *** 58 66 46.93% 0.1[-0.25,0.45]
Total *** 99 110 100% 0.36[-0.09,0.8]

Informed decisions.

balance programme, Outcome 3 Visual memory functions (immediate).
Blumenthal 1989 31 -5.5 (3.3) 34 -5.6 (3.7) 100% 0.05[-1.65,1.76]
Subtotal *** 31 34 100% 0.05[-1.65,1.76]

Total *** 31 34 100% 0.05[-1.65,1.76]

Analysis 3.4. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 4 Working memory.
Blumenthal 1989 31 7.9 (2.9) 34 6.9 (2.3) 30% 0.95[-0.31,2.21]
Kramer 2001 58 7.2 (1.8) 66 7.1 (2.1) 70% 0.1[-0.59,0.79]
Subtotal *** 89 100 100% 0.36[-0.41,1.12]
Total *** 89 100 100% 0.36[-0.41,1.12]


balance programme, Outcome 5 Memory functions (delayed).
Informed decisions.
Kramer 2001 58 11.4 (2.7) 66 10.9 (2.6) 61.83% 0.19[-0.17,0.54]
Subtotal *** 58 66 61.83% 0.19[-0.17,0.54]

Oken 2006 38 7 (2) 38 7.2 (1.9) 38.17% -0.1[-0.55,0.35]
Subtotal *** 38 38 38.17% -0.1[-0.55,0.35]
Total *** 96 104 100% 0.08[-0.2,0.36]

Analysis 3.6. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 6 Executive functions.
Blumenthal 1989 31 -79.5 (27.6) 34 -90.9 (34) 25.64% 0.36[-0.13,0.85]
Subtotal *** 31 34 25.64% 0.36[-0.13,0.85]

reasoning
Moul 1995 10 27.3 (3.5) 10 23 (4.1) 9.52% 1.08[0.13,2.03]
Subtotal *** 10 10 9.52% 1.08[0.13,2.03]


Kramer 2001 58 95.8 (6.3) 66 95.6 (7.4) 36.41% 0.03[-0.32,0.38]
Subtotal *** 58 66 36.41% 0.03[-0.32,0.38]

Informed decisions.

Oken 2006 38 10.7 (2.8) 38 10.5 (2.6) 28.43% 0.07[-0.38,0.52]
Subtotal *** 38 38 28.43% 0.07[-0.38,0.52]
Total *** 137 148 100% 0.23[-0.09,0.55]

Analysis 3.7. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 7 Perception.
Kramer 2001 58 75.1 (18.3) 66 71.4 (23.6) 86.44% 0.17[-0.18,0.53]
Subtotal *** 58 66 86.44% 0.17[-0.18,0.53]

Moul 1995 10 27.7 (3.8) 10 26 (2.9) 13.56% 0.48[-0.41,1.38]
Subtotal *** 10 10 13.56% 0.48[-0.41,1.38]

Total *** 68 76 100% 0.22[-0.11,0.54]

Analysis 3.8. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 8 Cognitive inhibition.
Blumenthal 1989 31 -1.7 (6.3) 34 -1.2 (6.1) 24.56% -0.07[-0.55,0.42]
Oken 2006 38 -10.8 (4.3) 38 -10 (4.6) 28.67% -0.18[-0.63,0.27]
Informed decisions.
Subtotal *** 69 72 53.22% -0.13[-0.46,0.2]

Kramer 2001 58 93.1 (132.5) 66 92.3 (150.3) 46.78% 0.01[-0.35,0.36]
Subtotal *** 58 66 46.78% 0.01[-0.35,0.36]
Total *** 127 138 100% -0.06[-0.31,0.18]

Analysis 3.9. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 9 Visual attention.

3.9.3 2&7 test

Blumenthal 1989 31 -6.8 (5.1) 34 -9.1 (9.3) 24.41% 0.3[-0.19,0.79]
Subtotal *** 31 34 24.41% 0.3[-0.19,0.79]

Kramer 2001 58 97.8 (3.3) 66 97 (3) 46.66% 0.25[-0.1,0.6]
Subtotal *** 58 66 46.66% 0.25[-0.1,0.6]

Oken 2006 38 -37.1 (34.1) 38 -40.3 (36.8) 28.92% 0.09[-0.36,0.54]
Subtotal *** 38 38 28.92% 0.09[-0.36,0.54]
Total *** 127 138 100% 0.22[-0.03,0.46]
Informed decisions.

balance programme, Outcome 10 Auditory attention.
Blumenthal 1989 31 8.9 (2.6) 34 8.6 (2) 31.14% 0.33[-0.81,1.46]
Kramer 2001 58 8 (2) 66 8.4 (2.1) 68.86% -0.4[-1.12,0.32]
Subtotal *** 89 100 100% -0.17[-0.83,0.49]
Total *** 89 100 100% -0.17[-0.83,0.49]

Analysis 3.11. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 11 Motor function.
Blumenthal 1989 31 123.6 (14.3) 34 120.4 (18.8) 34.33% 0.19[-0.3,0.68]
Subtotal *** 31 34 34.33% 0.19[-0.3,0.68]

Kramer 2001 58 -29.6 (6.3) 66 -29.8 (6.6) 65.67% 0.02[-0.33,0.38]
Subtotal *** 58 66 65.67% 0.02[-0.33,0.38]
Total *** 89 100 100% 0.08[-0.2,0.37]

Informed decisions.
Analysis 3.12. Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 12 Drop-out.
Blumenthal 1989 2/33 2/33 7.3% 1[0.13,7.55]
Kramer 2001 25/83 25/91 69.17% 1.14[0.59,2.2]
Oken 2006 6/44 9/47 23.53% 0.67[0.22,2.06]
Total (95% CI) 170 181 100% 0.99[0.58,1.72]

Favours treatment 0.01 0.1 1 10 100 Favours control
Comparison 4. Aerobic exercise versus strength programme

studies partici-
pants
1 Verbal memory functions (immedi- 1 20 Mean Difference (IV, Fixed, 95% CI) 0.30 [-4.17, 4.77]
ate)
1.1 Randt Memory test story recall 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
1.2 16 words immediate recall 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
1.3 Ross Information Processing As- 1 20 Mean Difference (IV, Fixed, 95% CI) 0.30 [-4.17, 4.77]
sessment immediate memory
1.4 Wechsler Adult Intelligence Scales 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
logical memory immediate recall
1.5 Rey auditory verbal learning trial 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
I-V
2 Executive functions 1 20 Mean Difference (IV, Fixed, 95% CI) -2.30 [-4.49, -0.11]
2.1 Trailmaking part B 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
2.2 Ross Information Processing As- 1 20 Mean Difference (IV, Fixed, 95% CI) -2.30 [-4.49, -0.11]
sessment problem solving and ab-
stract reasoning
2.3 Wechsler Memory Scales mental 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
control
2.4 Word comparison (#error) 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
2.5 Task switching paradigm (accura- 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
cy)
2.6 Verbal fluency 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
Informed decisions.

studies partici-
pants
3 Perception 1 20 Mean Difference (IV, Fixed, 95% CI) -0.5 [-2.93, 1.93]
3.1 Face recognition (delayed recall) 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
3.2 Ross Information Processing As- 1 20 Mean Difference (IV, Fixed, 95% CI) -0.5 [-2.93, 1.93]
sessment auditory processing
3.3 Wechsler Adult Intelligence Scales 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
visual reproduction
4 Cognitive speed 1 37 Mean Difference (IV, Fixed, 95% CI) -4.0 [-27.93, 19.93]
4.1 Simple reaction time 1 37 Mean Difference (IV, Fixed, 95% CI) -4.0 [-27.93, 19.93]
Analysis 4.1. Comparison 4 Aerobic exercise versus strength

programme, Outcome 1 Verbal memory functions (immediate).


Moul 1995 10 23.5 (3.5) 10 23.2 (6.3) 100% 0.3[-4.17,4.77]
Subtotal *** 10 10 100% 0.3[-4.17,4.77]


Total *** 10 10 100% 0.3[-4.17,4.77]

Informed decisions.

Analysis 4.2. Comparison 4 Aerobic exercise versus strength programme, Outcome 2 Executive functions.

reasoning
Moul 1995 10 27.3 (3.5) 10 29.6 (0.6) 100% -2.3[-4.49,-0.11]
Subtotal *** 10 10 100% -2.3[-4.49,-0.11]

4.2.4 Word comparison (#error)



Total *** 10 10 100% -2.3[-4.49,-0.11]

Informed decisions.
Analysis 4.3. Comparison 4 Aerobic exercise versus strength programme, Outcome 3 Perception.

Moul 1995 10 27.7 (3.8) 10 28.2 (1) 100% -0.5[-2.93,1.93]
Subtotal *** 10 10 100% -0.5[-2.93,1.93]

Total *** 10 10 100% -0.5[-2.93,1.93]

Analysis 4.4. Comparison 4 Aerobic exercise versus strength programme, Outcome 4 Cognitive speed.
Panton 1990 17 -274 (28.9) 20 -270 (44.7) 100% -4[-27.93,19.93]
Subtotal *** 17 20 100% -4[-27.93,19.93]
Total *** 17 20 100% -4[-27.93,19.93]

Favours treatment -100 -50 0 50 100 Favours control
Comparison 5. Fitness Improved: aerobic exercise versus any active intervention

studies partici-
pants
95% CI)
Informed decisions.

studies partici-
pants
1.1 Simple reaction time 1 37 Std. Mean Difference (IV, Random, -0.10 [-0.75, 0.54]
95% CI)
95% CI)
1.3 Trailmaking part A 1 49 Std. Mean Difference (IV, Random, -0.36 [-0.96, 0.24]
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
2.4 Wechsler Adult Intelligence Scales log- 1 24 Std. Mean Difference (IV, Random, -1.41 [-2.36, -0.45]
95% CI)
2.6 Hopkins Verbal Learning Test (imme- 1 49 Std. Mean Difference (IV, Random, 0.34 [-0.27, 0.94]
diate) 95% CI)
3 Visual memory functions (immediate) 2 89 Mean Difference (IV, Random, 95% -0.59 [-2.04, 0.87]
CI)
3.1 Benton visual retention (#error) 1 65 Mean Difference (IV, Random, 95% 0.05 [-1.65, 1.76]
CI)
3.2 Wechsler Memory Scales visual repro- 1 24 Mean Difference (IV, Random, 95% -1.45 [-3.50, 0.60]
duction CI)
95% CI)
95% CI)
4.2 2-Back (accuracy, Hits - False Alarms) 1 49 Std. Mean Difference (IV, Random, -0.14 [-0.74, 0.46]
95% CI)
5 Memory functions (delayed) 2 173 Mean Difference (IV, Random, 95% 0.48 [-0.29, 1.25]
CI)
Informed decisions.

studies partici-
pants
5.1 16 words delayed recall 0 0 Mean Difference (IV, Random, 95% 0.0 [0.0, 0.0]
CI)
5.2 Rey auditory verbal learning delayed 1 124 Mean Difference (IV, Random, 95% 0.5 [-0.44, 1.44]
recall trial CI)
5.3 10 words delayed recall 0 0 Mean Difference (IV, Random, 95% 0.0 [0.0, 0.0]
CI)
5.4 Hopkins Verbal Learning Test - 12 1 49 Mean Difference (IV, Random, 95% 0.44 [-0.94, 1.82]
words (delayed) CI)
95% CI)
95% CI)
soning
6.3 Wechsler Memory Scales mental con- 1 24 Std. Mean Difference (IV, Random, -0.31 [-1.16, 0.55]
trol 95% CI)
95% CI)
95% CI)
6.6 Letter number sequencing 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
7 Perception 3 178 Std. Mean Difference (IV, Random, -0.01 [-0.50, 0.48]
95% CI)
95% CI)
7.3 Wechsler Adult Intelligence Scales vi- 1 24 Std. Mean Difference (IV, Random, -0.73 [-1.61, 0.15]
95% CI)
95% CI)
95% CI)
Informed decisions.

studies partici-
pants
8.3 Flanker Task (Incongruent RT) 1 49 Std. Mean Difference (IV, Random, 0.00 [-0.59, 0.60]
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
9.5 Covert orienting of visuospatial atten- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
tion 95% CI)
10 Auditory attention 3 213 Mean Difference (IV, Random, 95% 0.15 [-0.49, 0.79]
CI)
10.1 Digit span forward 3 213 Mean Difference (IV, Random, 95% 0.15 [-0.49, 0.79]
CI)
95% CI)
95% CI)
95% CI)
Analysis 5.1. Comparison 5 Fitness Improved: aerobic exercise

versus any active intervention, Outcome 1 Cognitive speed.
Panton 1990 17 -274 (28.9) 20 -270 (44.7) 16.81% -0.1[-0.75,0.54]
Subtotal *** 17 20 16.81% -0.1[-0.75,0.54]
Informed decisions.

Legault 2011 16 -37.4 (11.3) 33 -34.2 (7.2) 18.87% -0.36[-0.96,0.24]
Subtotal *** 16 33 18.87% -0.36[-0.96,0.24]

Blumenthal 1989 31 52.5 (8.6) 34 48.7 (10) 25.5% 0.4[-0.09,0.9]
Kramer 2001 58 96.5 (3.9) 66 95.7 (6.3) 38.83% 0.15[-0.2,0.5]
Subtotal *** 89 100 64.32% 0.24[-0.05,0.52]
Total *** 122 153 100% 0.08[-0.22,0.37]

Analysis 5.2. Comparison 5 Fitness Improved: aerobic exercise versus any

active intervention, Outcome 2 Verbal memory functions (immediate).

Blumenthal 1989 31 11.1 (3.9) 34 9.8 (3.5) 23.11% 0.34[-0.15,0.83]
Subtotal *** 31 34 23.11% 0.34[-0.15,0.83]

Moul 1995 10 23.5 (3.5) 20 19.6 (7.3) 16.62% 0.6[-0.18,1.37]
Subtotal *** 10 20 16.62% 0.6[-0.18,1.37]

Fabre 2002 8 7.4 (1) 16 9.1 (1.2) 13.42% -1.41[-2.36,-0.45]
Subtotal *** 8 16 13.42% -1.41[-2.36,-0.45]
Informed decisions.
Test for overall effect: Z=2.89(P=0)

Kramer 2001 58 10 (1.8) 66 9.8 (2.1) 26.42% 0.1[-0.25,0.45]
Subtotal *** 58 66 26.42% 0.1[-0.25,0.45]

Legault 2011 16 6.4 (1.8) 33 5.8 (1.6) 20.44% 0.34[-0.27,0.94]
Subtotal *** 16 33 20.44% 0.34[-0.27,0.94]
Total *** 123 169 100% 0.08[-0.38,0.55]

Analysis 5.3. Comparison 5 Fitness Improved: aerobic exercise versus any

active intervention, Outcome 3 Visual memory functions (immediate).
Blumenthal 1989 31 -5.5 (3.3) 34 -5.6 (3.7) 57.44% 0.05[-1.65,1.76]
Subtotal *** 31 34 57.44% 0.05[-1.65,1.76]

Fabre 2002 8 10.2 (2.8) 16 11.7 (1.3) 42.56% -1.45[-3.5,0.6]
Subtotal *** 8 16 42.56% -1.45[-3.5,0.6]
Total *** 39 50 100% -0.59[-2.04,0.87]

Informed decisions.

versus any active intervention, Outcome 4 Working memory.
Blumenthal 1989 31 7.9 (2.9) 34 6.9 (2.3) 27.69% 0.37[-0.12,0.86]
Kramer 2001 58 7.2 (1.8) 66 7.1 (2.1) 53.63% 0.05[-0.3,0.4]
Subtotal *** 89 100 81.32% 0.16[-0.13,0.45]

Legault 2011 16 0.6 (0.2) 33 0.6 (0.2) 18.68% -0.14[-0.74,0.46]
Subtotal *** 16 33 18.68% -0.14[-0.74,0.46]
Total *** 105 133 100% 0.1[-0.16,0.36]

Analysis 5.5. Comparison 5 Fitness Improved: aerobic exercise versus

any active intervention, Outcome 5 Memory functions (delayed).

Kramer 2001 58 11.4 (2.7) 66 10.9 (2.6) 68.43% 0.5[-0.44,1.44]
Subtotal *** 58 66 68.43% 0.5[-0.44,1.44]


Legault 2011 16 9.4 (2.2) 33 8.9 (2.5) 31.57% 0.44[-0.94,1.82]
Subtotal *** 16 33 31.57% 0.44[-0.94,1.82]
Total *** 74 99 100% 0.48[-0.29,1.25]
Informed decisions.


versus any active intervention, Outcome 6 Executive functions.
Blumenthal 1989 31 -79.5 (27.6) 34 -90.9 (34) 22.25% 0.36[-0.13,0.85]
Legault 2011 15 -81.5 (49.1) 33 -86.2 (28.5) 20.87% 0.13[-0.48,0.74]
Subtotal *** 46 67 43.12% 0.27[-0.11,0.65]

reasoning
Moul 1995 10 27.3 (3.5) 20 18.5 (2.9) 15.38% 2.75[1.69,3.82]
Subtotal *** 10 20 15.38% 2.75[1.69,3.82]
Test for overall effect: Z=5.06(P<0.0001)

Fabre 2002 8 5.9 (0.9) 16 6.2 (1) 17.88% -0.31[-1.16,0.55]
Subtotal *** 8 16 17.88% -0.31[-1.16,0.55]

Kramer 2001 58 95.8 (6.3) 66 95.6 (7.4) 23.62% 0.03[-0.32,0.38]
Subtotal *** 58 66 23.62% 0.03[-0.32,0.38]


Total *** 122 169 100% 0.48[-0.18,1.15]

Heterogeneity: Tau2=0.46; Chi2=24.7, df=4(P<0.0001); I2=83.81%
Informed decisions.
Test for subgroup differences: Chi2=24.35, df=1 (P<0.0001), I2=87.68%
Analysis 5.7. Comparison 5 Fitness Improved: aerobic

exercise versus any active intervention, Outcome 7 Perception.
Kramer 2001 58 75.1 (18.3) 66 71.4 (23.6) 52.02% 0.17[-0.18,0.53]
Subtotal *** 58 66 52.02% 0.17[-0.18,0.53]

Moul 1995 10 27.7 (3.8) 20 27.1 (2.1) 26.25% 0.21[-0.55,0.97]
Subtotal *** 10 20 26.25% 0.21[-0.55,0.97]

Fabre 2002 8 10.2 (2.8) 16 11.7 (1.3) 21.72% -0.73[-1.61,0.15]
Subtotal *** 8 16 21.72% -0.73[-1.61,0.15]
Total *** 76 102 100% -0.01[-0.5,0.48]


versus any active intervention, Outcome 8 Cognitive inhibition.
Blumenthal 1989 31 -1.7 (6.3) 34 -1.2 (6.1) 28.01% -0.07[-0.55,0.42]
Subtotal *** 31 34 28.01% -0.07[-0.55,0.42]

Kramer 2001 58 93.1 (132.5) 66 92.3 (150.3) 53.36% 0.01[-0.35,0.36]
Subtotal *** 58 66 53.36% 0.01[-0.35,0.36]
Informed decisions.

Legault 2011 16 -538.8 33 -539.1 18.63% 0[-0.59,0.6]
(67.9) (80.5)
Subtotal *** 16 33 18.63% 0[-0.59,0.6]
Total *** 105 133 100% -0.02[-0.27,0.24]


versus any active intervention, Outcome 9 Visual attention.

5.9.3 2&7 test

Blumenthal 1989 31 -6.8 (5.1) 34 -9.1 (9.3) 34.35% 0.3[-0.19,0.79]
Subtotal *** 31 34 34.35% 0.3[-0.19,0.79]

Kramer 2001 58 97.8 (3.3) 66 97 (3) 65.65% 0.25[-0.1,0.6]
Subtotal *** 58 66 65.65% 0.25[-0.1,0.6]

Total *** 89 100 100% 0.27[-0.02,0.56]

Informed decisions.

versus any active intervention, Outcome 10 Auditory attention.
Blumenthal 1989 31 8.9 (2.6) 34 8.6 (2) 21.72% 0.33[-0.81,1.46]
Fabre 2002 8 6.1 (0.7) 16 5.6 (0.8) 41.51% 0.55[-0.08,1.18]
Kramer 2001 58 8 (2) 66 8.4 (2.1) 36.76% -0.4[-1.12,0.32]
Subtotal *** 97 116 100% 0.15[-0.49,0.79]
Total *** 97 116 100% 0.15[-0.49,0.79]


versus any active intervention, Outcome 11 Motor function.
Blumenthal 1989 31 123.6 (14.3) 34 120.4 (18.8) 34.33% 0.19[-0.3,0.68]
Subtotal *** 31 34 34.33% 0.19[-0.3,0.68]

Kramer 2001 58 -29.6 (6.3) 66 -29.8 (6.6) 65.67% 0.02[-0.33,0.38]
Subtotal *** 58 66 65.67% 0.02[-0.33,0.38]
Total *** 89 100 100% 0.08[-0.2,0.37]

Informed decisions.
Analysis 5.12. Comparison 5 Fitness Improved: aerobic

exercise versus any active intervention, Outcome 12 Drop-out.
Blumenthal 1989 2/33 2/33 9.16% 1[0.13,7.55]
Fabre 2002 0/8 0/16 Not estimable
Kramer 2001 25/83 25/91 86.78% 1.14[0.59,2.2]
Legault 2011 3/18 0/18 4.06% 8.35[0.4,174.5]
Total (95% CI) 152 178 100% 1.22[0.66,2.25]

Comparison 6. Fitness improved: aerobic exercise versus no intervention

studies partici-
pants
95% CI)
95% CI)
1.2 Choice reaction time 1 14 Std. Mean Difference (IV, Random, -0.53 [-1.60, 0.54]
95% CI)
1.3 Trailmaking part A 1 72 Std. Mean Difference (IV, Random, 0.31 [-0.15, 0.78]
95% CI)
95% CI)
95% CI)
2.1 Randt Memory test story recall 1 65 Std. Mean Difference (IV, Random, -0.04 [-0.53, 0.45]
95% CI)
95% CI)
95% CI)
Informed decisions.

studies partici-
pants
2.6 Hopkins Verbal Learning Test (imme- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
diate) 95% CI)
3 Visual memory functions (immediate) 1 65 Mean Difference (IV, Random, 95% CI) -0.28 [-1.87, 1.30]
3.1 Benton visual retention (#error) 1 65 Mean Difference (IV, Random, 95% CI) -0.28 [-1.87, 1.30]
3.2 Wechsler Memory Scales visual repro- 0 0 Mean Difference (IV, Random, 95% CI) 0.0 [0.0, 0.0]
duction
95% CI)
95% CI)
4.2 2-Back (accuracy, Hits - False Alarms) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
5 Memory functions (delayed) 1 72 Mean Difference (IV, Fixed, 95% CI) 0.92 [-0.75, 2.59]
5.1 Rey auditory verbal learning delayed 1 72 Mean Difference (IV, Fixed, 95% CI) 0.92 [-0.75, 2.59]
recall trial
95% CI)
95% CI)
soning
trol 95% CI)
6.4 Task switching paradigm (accuracy) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
6.6 Letter number sequencing 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
7 Cognitive inhibition 2 137 Std. Mean Difference (IV, Random, 0.29 [-0.04, 0.63]
95% CI)
7.1 Stroop colour word (interference) 2 137 Std. Mean Difference (IV, Random, 0.29 [-0.04, 0.63]
95% CI)
7.2 Stopping task (accuracy choice RT) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
Informed decisions.

studies partici-
pants
7.3 Flanker Task (Incongruent RT) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
95% CI)
95% CI)
95% CI)
95% CI)
8.4 Visual search (accuracy) 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
95% CI)
8.5 Covert orienting of visuospatial atten- 0 0 Std. Mean Difference (IV, Random, 0.0 [0.0, 0.0]
tion 95% CI)
9 Auditory attention 1 65 Mean Difference (IV, Fixed, 95% CI) 0.16 [-1.01, 1.33]
9.1 Digit span forward 1 65 Mean Difference (IV, Fixed, 95% CI) 0.16 [-1.01, 1.33]
10 Motor function 1 65 Mean Difference (IV, Fixed, 95% CI) 0.10 [-7.87, 8.08]
10.1 Finger tapping 1 65 Mean Difference (IV, Fixed, 95% CI) 0.10 [-7.87, 8.08]
10.2 Pursuit rotor task (tracking error) 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
11 Drop-out 3 164 Odds Ratio (IV, Random, 95% CI) 1.50 [0.50, 4.50]
Analysis 6.1. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 1 Cognitive speed.
Panton 1990 17 -274 (28.9) 12 -275 (52) 16.2% 0.02[-0.71,0.76]
Subtotal *** 17 12 16.2% 0.02[-0.71,0.76]

Whitehurst 1991 7 -0.4 (0) 7 -0.4 (0) 7.73% -0.53[-1.6,0.54]
Subtotal *** 7 7 7.73% -0.53[-1.6,0.54]
Informed decisions.
Langlois 2012 36 -44.1 (13.4) 36 -49.5 (20.2) 40.2% 0.31[-0.15,0.78]
Subtotal *** 36 36 40.2% 0.31[-0.15,0.78]

Blumenthal 1989 31 52.5 (9) 34 48.2 (10.2) 35.86% 0.44[-0.05,0.94]
Subtotal *** 31 34 35.86% 0.44[-0.05,0.94]
Total *** 91 89 100% 0.25[-0.05,0.55]

Analysis 6.2. Comparison 6 Fitness improved: aerobic exercise versus

no intervention, Outcome 2 Verbal memory functions (immediate).
Blumenthal 1989 31 11.1 (3.9) 34 11.2 (3.8) 47.53% -0.04[-0.53,0.45]
Subtotal *** 31 34 47.53% -0.04[-0.53,0.45]




Langlois 2012 36 10.9 (3.1) 36 10.2 (3.8) 52.47% 0.21[-0.25,0.67]
Subtotal *** 36 36 52.47% 0.21[-0.25,0.67]
Informed decisions.

Total *** 67 70 100% 0.09[-0.24,0.43]

Analysis 6.3. Comparison 6 Fitness improved: aerobic exercise versus

no intervention, Outcome 3 Visual memory functions (immediate).
Blumenthal 1989 31 -5.5 (3.3) 34 -5.3 (3.2) 100% -0.28[-1.87,1.3]
Subtotal *** 31 34 100% -0.28[-1.87,1.3]

Total *** 31 34 100% -0.28[-1.87,1.3]

Analysis 6.4. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 4 Working memory.
Blumenthal 1989 31 7.8 (2.9) 34 7.3 (2.2) 47.3% 0.18[-0.31,0.67]
Langlois 2012 36 6.6 (2.5) 36 6.5 (2.5) 52.7% 0.07[-0.39,0.53]
Subtotal *** 67 70 100% 0.12[-0.21,0.46]

Informed decisions.
Total *** 67 70 100% 0.12[-0.21,0.46]

Analysis 6.5. Comparison 6 Fitness improved: aerobic exercise

versus no intervention, Outcome 5 Memory functions (delayed).
Langlois 2012 36 10.6 (3.2) 36 9.6 (4) 100% 0.92[-0.75,2.59]
Subtotal *** 36 36 100% 0.92[-0.75,2.59]
Total *** 36 36 100% 0.92[-0.75,2.59]


versus no intervention, Outcome 6 Executive functions.
Blumenthal 1989 31 -79.5 (27.6) 34 -81.5 (36.3) 49.09% 0.06[-0.43,0.55]
Langlois 2012 36 -104.9 36 -136.2 50.91% 0.53[0.06,1]
(37.9) (72.9)
Subtotal *** 67 70 100% 0.3[-0.16,0.76]

reasoning

Informed decisions.



Total *** 67 70 100% 0.3[-0.16,0.76]


versus no intervention, Outcome 7 Cognitive inhibition.
Blumenthal 1989 31 -1.7 (6.3) 34 -4.5 (6.7) 46.87% 0.44[-0.06,0.93]
Langlois 2012 36 -141.7 36 -149.4 (43) 53.13% 0.17[-0.29,0.63]
(46.5)
Subtotal *** 67 70 100% 0.29[-0.04,0.63]


Total *** 67 70 100% 0.29[-0.04,0.63]

Informed decisions.
Analysis 6.8. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 8 Visual attention.

6.8.3 2&7 test

Blumenthal 1989 31 6.8 (5.1) 34 6.6 (5) 100% 0.04[-0.44,0.53]
Subtotal *** 31 34 100% 0.04[-0.44,0.53]


Total *** 31 34 100% 0.04[-0.44,0.53]


versus no intervention, Outcome 9 Auditory attention.
Blumenthal 1989 31 8.9 (2.6) 34 8.8 (2.2) 100% 0.16[-1.01,1.33]
Subtotal *** 31 34 100% 0.16[-1.01,1.33]
Informed decisions.

Total *** 31 34 100% 0.16[-1.01,1.33]

Analysis 6.10. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 10 Motor function.
Blumenthal 1989 31 123.6 (14.3) 34 123.5 (18.4) 100% 0.1[-7.87,8.08]
Subtotal *** 31 34 100% 0.1[-7.87,8.08]

Total *** 31 34 100% 0.1[-7.87,8.08]

Favours aerobic -10 -5 0 5 10 Favours control
Analysis 6.11. Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 11 Drop-out.
n/N n/N IV, Random, 95% CI IV, Random, 95% CI
Blumenthal 1989 2/33 2/34 29.66% 1.03[0.14,7.79]
Langlois 2012 7/43 4/40 70.34% 1.75[0.47,6.5]
Whitehurst 1991 0/7 0/7 Not estimable
Total (95% CI) 83 81 100% 1.5[0.5,4.5]

Favours treatment 0.01 0.1 1 10 100 Favours control
ADDITIONAL TABLES
Informed decisions.
Table 1. Grouping of cognitive tests and studies over cognitive functions

Cognitive function Cognitive tests Trial
Cognitive speed Simple RT Panton 1990, Oken 2006
Choice RT Hassmén 1997, Whitehurst 1991
Trailmaking part A Emery 1998, Legault 2011, Langlois 2012
Digit symbol substitution Blumenthal 1989, Kramer 2001, Emery

1990a
Verbal memory func- Randt memory test story recall Blumenthal 1989
tions (immediate)
16 words immediate recall Hassmén 1997
Ross Information Processing Assessment memory immediate Moul 1995

recall
Wechsler Adult Intelligence Scales logical memory immediate Fabre 2002

recall
Rey auditory verbal learning test trail I-V Kramer 2001, Langlois 2012
Hopkins Verbal Learning Test Legault 2011
Visual memory func- Benton visual retention Blumenthal 1989

tions (immediate)
Wechsler Memory Scales visual reproduction immediate recall Fabre 2002
Working memory Digit span backward Blumenthal 1989, Kramer 2001, Langlois
2012
2-Back Legault 2011
Memory function 16 words delayed recall Hassmén 1997

(delayed)
Rey auditory verbal learning test delayed recall trail Kramer 2001, Langlois 2012
10 words delayed recall Oken 2006
Hopkins Verbal Learning Test - 12 words Legault 2011
Executive functions Trailmaking part B Blumenthal 1989, Legault 2011, Langlois

2012
Ross Information Processing Assessment problem solving and Moul 1995

abstract reasoning
Wechsler Memory Scales mental control Fabre 2002
Task switching paradigm Kramer 2001
Verbal fluency Emery 1990a
Letter number sequencing Oken 2006
Informed decisions.
Table 1. Grouping of cognitive tests and studies over cognitive functions (Continued)
Perception Face recognition Hassmén 1997, Kramer 2001
Ross Information Processing Assessment auditory processing Moul 1995
Wechsler Adult Intelligence Scales visual reproduction Fabre 2002
Cognitive inhibition Stroop colour word test Blumenthal 1989, Oken 2006, Langlois
2012, Predovan 2012
Stopping task Kramer 2001
Flanker Task Legault 2011
Visual attention Digit vigilance Emery 1990a
Tracking Bakken 2001
2&7 test Blumenthal 1989
Visual search Kramer 2001
Covert orienting of visuospatial attention Oken 2006
Auditory attention Digit span forward Blumenthal 1989, Emery 1990a, Fabre
2002, Hassmén 1997, Kramer 2001
Motor function Finger tapping Bakken 2001, Blumenthal 1989, Emery

1998
Pursuit rotor task Kramer 2001
Table 2. Types of interventions in each trial
Trial Aerobic ex- Strength Flexibili- Social Cognitive Education Miscella- No inter-
ercise ty/balance neous vention
Library
Cochrane
Bakken 2001 x - - - - - - x
Blumenthal 1989 x - x - - - - x
Emery 1990a x - - x - - - x
Better health.
Informed decisions.
Trusted evidence.
Fabre 2002 x - - x x - - -
Kramer 2001 x - x - - - - -
Langlois 2012 x - - - - - - x
Legault 2011 x - - - x x - -
Madden 1989 x - x - - - - x
Moul 1995 x x x - - - - -
Oken 2006 x - x - - - - x
Panton 1990 x x - - - - - x
Whitehurst 1991 x - - - - - - x
Table 3. Methodological quality of included trials (CLEAR NPT score)

Study ID Number
1/2 3 4 5 6 / 6.1.1 / 6.1.2 7 / 7.1.1 / 7.1.2 8/ 9 10 Total

8.1.1
Bakken 2001 3/3 1 3 1 2/3/2 2/3/2 1/0 1 2 28
Blumenthal 1989 3/3 1 3 1 2/2/2 2/2/2 4/3 1 3 34
Emery 1990a 3/3 1 3 1 2/2/2 2/2/2 4/3 1 2 33

106
Table 3. Methodological quality of included trials (CLEAR NPT score) (Continued)
Fabre 2002 3/3 1 3 2 2/1/1 2/1/1 4/3 1 1 29
Library
Cochrane
Kramer 2001 3/3 1 3 1 2/3/1 2/3/1 4/3 1 2 33
Langlois 2012 3/3 1 3 3 2/3/2 2/3/2 4/3 1 2 37
Legault 2011 3/3 1 3 1 2/3/1 2/3/1 4/3 1 1 31
Better health.
Informed decisions.
Trusted evidence.
Madden 1989 3/3 1 3 1 2/3/2 2/3/2 4/3 1 2 34
Moul 1995 3/3 1 3 3 2/3/1 2/3/1 4/3 1 1 34
Oken 2006 1/1 1 3 1 2 / 2 /1 2/2/1 1/3 1 2 24
Panton 1990 3/3 1 3 2 2/3/3 2/3/3 4/3 1 2 38
Whitehurst 1991 3/3 1 3 2 2/3/3 2/3/3 4/3 1 3 39
See Table 4 for CLEAR NPT items.

107
Informed decisions.
Table 4. CLEAR NPT checklist items

Number Checklist item
1 Was the generation of allocation sequences adequate?
2 Was the treatment allocation concealed?
3 Were the details of the intervention administered to each group made available?a
4 Were care providers' experience or skillb in each arm appropriate?c
5 Was participant (i.e. patients) adherence assessed quantitatively?d
6 Were participants adequately blinded?
6.1.1 If participants were not adequately blinded, were all other treatments and care (cointerventions)
the same in each randomised group?
6.1.2 If participants were not adequately blinded, were withdrawals and lost to follow-up the same in
each randomised group?
7 Were care providers or persons caring for the participants adequately blinded?
7.1.1 If care providers were not adequately blinded, were all other treatments and care (cointerventions)
the same in each randomised group?
7.1.2 If care providers were not adequately blinded, were withdrawals and losses to follow-up the same
in each randomised group?
8 Were outcome assessors adequately blinded to assess the primary outcomes?
8.1.1 If outcome assessors were not adequately blinded, were specific methods used to avoid ascertain-
ment bias?e
9 Was the follow-up schedule the same in each group?f
10 Were the main outcomes analysed according to the ITT principle?
a The answer should be "Yes" if these data are either described in the report or made available for
each arm (reference to preliminary report, online addendum, etc.).
b Care provider experience or skill will be assessed only for therapist-dependent interventions
(where the success of the intervention is directly linked to the providers' technical skill. For other
treatment this item is not relevant and should be answered "Unclear".
c Appropriate experience or skill should be determined according to published data, preliminary

studies, guidelines, run-in period, or a group of experts and should be specified in the protocol for
each study arm before the beginning of the survey.
d Treatment adherence will be assessed only for the treatments necessitating iterative interven-
tions (physiotherapy that supposes several sessions, in contrast to a one-shot treatment such as
surgery). For one-shot treatments, this item is not relevant and should be answered "Unclear".
e The answer is "0" if the answer to 8 is "Yes". The answer should be "Yes" if the main outcome is ob-
jective or hard, or if outcomes were assessed by a blinded or at least an independent endpoint re-
Informed decisions.
Table 4. CLEAR NPT checklist items (Continued)

view committee, or if outcomes were assessed by an independent outcome assessor trained to per-
form the measurements in a standardised manner, or if the outcome assessor was blinded to the
study purpose and hypothesis.
f This item is not relevant if follow-up is part of the question. For example, this item is not relevant
for a trial assessing frequent versus less frequent follow-up for cancer recurrence. In these situa-
tions, this item should be answered "Unclear".
For items 6, 7 and 8 a score of 1 was given for a "Yes", a score of 2 for "No, because blinding is not feasible", a score of 3 for "No, al-
though blinding is feasible" and a score of 4 for "Unclear". The other items of the checklist (1 to 5, 6.1.1, 6.1.2, 7.1.1, 7.1.2, 8.1.1, 9 and
10) were given a score of 1 for "Yes", 2 for "No" and 3 for "Unclear".
APPENDICES
Appendix 1. Search strategies: August 2013
Source Search strategy Hits retrieved
1. ALOIS (www.med- Keyword search: "physical activity" OR exercise 8

icine.ox.ac.uk/alois)
- all dates to August
2013
2. MEDLINE In- 1. exercise.mp. or Exercise/ 650

process and other
non-indexed cita- 2. exercis*.mp.
tions and MEDLINE
3. motor activit*.mp. [mp=title, abstract, original title, name of substance word,
1946 to August 2013
subject heading word, keyword heading word, protocol supplementary concept,
(Ovid SP)
rare disease supplementary concept, unique identifier]
4. leisure activit*.mp.
5. physical fitness.mp.
6. physical endurance.mp. or Physical Endurance/
7. exercise tolerance.mp. or Exercise Tolerance/
8. aerobic.mp.
9. physical activity.mp.
10. Motor Activity/
11. physical capacity.mp.
12. physical performance training.mp.
13. cognit*.mp.
14. Mental Processes/ or mental process*.mp.
15. maximal VO2.mp.
Informed decisions.
(Continued)
16. METS.mp.
17. Watts.mp.
18. treadmill speed.mp.
19. inclination.mp.
20. Adult/ or adult*.mp.
21. middle aged.mp. or Middle Aged/
22. aged.mp. or Aged/
23. elderly.mp.
24. old*.mp.
25. geriatric.mp. or Geriatrics/
26. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12
27. 13 or 14 or 15 or 16 or 17 or 18 or 19
28. 20 or 21 or 22 or 23 or 24 or 25
29. 26 and 27 and 28
30. randomised controlled trial.pt.
31. controlled clinical trial.pt.
32. randomized.ab.
33. placebo.ab.
34. drug therapy.fs.
35. randomly.ab.
36. trial.ab.
37. groups.ab.
38. or/30-37
39. 29 and 38
40. (2012* or 2013*).ed.
41. 39 and 40
3. EMBASE 1. exercise.mp. or Exercise/ 750
1974 to 2013 week 27 2. exercis*.mp.

(Ovid SP)
3. motor activit*.mp. [mp=title, abstract, subject headings, heading word, drug
trade name, original title, device manufacturer, drug manufacturer, device trade
name, keyword]
Informed decisions.
(Continued)
8. aerobic.mp.
10. Motor Activity/
13. cognit*.mp.
15. maximal VO2.mp.
16. METS.mp.
17. Watts.mp.
19. inclination.mp.
23. elderly.mp.
24. old*.mp.
27. 13 or 14 or 15 or 16 or 17 or 18 or 19
28. 20 or 21 or 22 or 23 or 24 or 25
29. 26 and 27 and 28
30. "randomi?ed controlled trial".mp. [mp=title, abstract, subject headings, heading

word, drug trade name, original title, device manufacturer, drug manufacturer, de-
vice trade name, keyword]
31. "controlled clinical trial".mp. [mp=title, abstract, subject headings, heading

word, drug trade name, original title, device manufacturer, drug manufacturer, de-
vice trade name, keyword]
32. random*.mp.
33. randomised controlled trial/
34. clinical trial.mp.
35. or/30-34
36. 29 and 35
37. (2012* or 2013*).em.
38. 36 and 37
4. PSYCINFO 1. exercise.mp. or Exercise/ 92
Informed decisions.
(Continued)
1806 to August week 2. exercis*.mp.
5 2011 (Ovid SP)
3. motor activit*.mp. [mp=title, abstract, heading word, table of contents, key con-
cepts, original title, tests & measures]
8. aerobic.mp.
10. Motor Activity/
13. cognit*.mp.
15. maximal VO2.mp.
16. METS.mp.
17. Watts.mp.
19. inclination.mp.
23. elderly.mp.
24. old*.mp.
27. 13 or 14 or 15 or 16 or 17 or 18 or 19
28. 20 or 21 or 22 or 23 or 24 or 25
29. 26 and 27 and 28
30. "randomi?ed controlled trial".mp. [mp=title, abstract, heading word, table of

contents, key concepts, original title, tests & measures]
31. "controlled clinical trial".mp. [mp=title, abstract, heading word, table of con-
tents, key concepts, original title, tests & measures]
32. random*.mp.
33. randomised controlled trial/
34. clinical trial.mp.

Informed decisions.
(Continued)
35. 30 or 31 or 32 or 33 or 34
36. 29 and 35
37. (2012* or 2013*).up.
38. 36 and 37
5. CINAHL (EBSCO- S1 TX exercis* 213

host) to August 2013
S2 TX "physical activit*"
S3 TX cycling
S4 TX swim*
S5 TX gym*
S6 TX walk* OR treadmill
S7 TX danc*
S8 TX yoga*
S9 TX "tai chi"
S10 (MH "Exercise+")
S11 (MH "Clinical Trials")
S12 TX trial
S13 TX RCT OR CCT
S14 TX placebo*
S15 TX "double-blind*" OR "single-blind*"
S16 TX groups OR "control group"
S17 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10
S18 S11 OR S12 OR S13 OR S14 OR S15 OR S16
S19 TX elderly
S20 (MH "Aged")
S21 TX geriatric
S22 S19 OR S20 OR S21
S23 TX cognition
S24 cognition
S25 (MH "Cognition")
S26 TX cognitive
S27 AB brain OR mental OR memory OR "executive function*"
S28 S23 OR S24 OR S25 OR S26 OR S27
S29 S17 AND S18 AND S22 AND S28
S30 EM 2012
Informed decisions.
(Continued)
S31 EM 2013
S32 S30 OR S31
S33 S29 AND S32
6. Web of Science Topic=("physical activity" OR "physical exercise" OR cycling OR yoga OR swim* OR 869
(1945 to August 2013) danc* OR aerobic*) AND Topic=(cogni* OR elderly OR memory OR geriatric) AND
(ISI Web of Knowl- Topic=(randomly OR trial OR RCT)
edge)
Timespan=2012-2013. Databases=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH,
BKCI-S, BKCI-SSH, CCR-EXPANDED, IC.
7. LILACS (BIREME) "exercício físico" OR "physical exercise" OR aerobic$ OR aeróbico OR aerobio OR yo- 165
All dates to August ga OR "physical activit$" OR "actividad física" OR "atividade física" [Words] and ran-
2013 domised OR randomized OR trial OR randomly OR groups [Words] and elderly OR
idoso OR anciano [Words]
8. CENTRAL (the #1 "cognit* impair*" 191

Cochrane Library; Is-
sue 2 of 4, 2013) #2 MeSH descriptor: [Cognition Disorders] explode all trees
#3 MCI
#4 ACMI
#5 ARCD
#6 SMC
#7 CIND
#8 BSF
#9 AAMI
#10 LCD
#11 QD or "questionable dementia"
#12 AACD
#13 MNCD
#14 MCD
#15 "N-MCI" or "A-MCI" or "M-MCI"
#16 (cognit* or memory or cerebr* or mental*) near/3 (declin* or impair* or los* or

deteriorat* or degenerat* or complain* or disturb* or disorder*)
#17 "preclinical AD"
#18 "pre-clinical AD"
#19 "preclinical alzheimer*" or "pre-clinical alzheimer*"
#20 aMCI or MCIa
#21 "CDR 0.5" or "clinical dementia rating scale 0.5"
#22 "GDS 3" or "stage 3 GDS"
#23 "global deterioration scale" and "stage 3"
#24 "Benign senescent forgetfulness"
Informed decisions.
(Continued)
#25 "mild neurocognit* disorder*"
#26 (prodrom* near/2 dement*)
#27 episodic* near/2 memory
#28 "preclinical dementia" or "pre-clinical dementia"
#29 episodic near/2 memory
#30 "pre-clinical dementia" or "preclinical dementia"
#31 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14

or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or
#27 or #28 or #29 or #30
#32 "Physical therap*"
#33 "physical activit*"
#34 fitness
#35 exercis*
#36 aerobic
#37 "physical* fit*"
#38 "physical capacity"
#39 "physical training"
#40 Cycling
#41 swim*
#42 gym*
#43 danc*
#44 yoga
#45 "tai chi"
#46 walk*
#47 flexibility
#48 motor*
#49 "leisure activit*"
#50 "physical endurance"
#51 MeSH descriptor: [Exercise Therapy] explode all trees
#52 #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or
#44 or #45 or #46 or #47 or #48 or #49 or #50 or #51 in Trials
#53 #31 and #52 from 2009 to 2011, in Trials
#54 #52 and (brain or MMSE or cognition or cognitive or memory) from 2012 to 2013,
in Trials
9. ClinicalTrials.gov Interventional Studies | cognition OR cognitive OR memory OR MMSE OR brain | 273

(www.clinicaltrial- "Physical therapy" OR "physical activity" OR "physical exercise" OR cycling OR
Informed decisions.
(Continued)
s.gov) All dates to Au- yoga OR swim OR swimming OR dance OR aerobic | Adult, Senior | received from
gust 2013 01/01/2012 to 08/03/2013
10. ICTRP Search Interventional Studies | cognition OR cognitive | "Physical therapy" OR "physical ac- 187
Portal (http:// tivity" OR "physical exercise" OR cycling OR yoga OR swim OR swimming OR dance
apps.who.int/tri- OR aerobic | Adult, Senior | received from 01/01/2012 to 08/03/2013
alsearch) [includes:
Australian New
Zealand Clinical Tri-
als Registry; Clinical-
Trilas.gov; ISRCTN;
Chinese Clinical Tri-
al Registry; Clinical
Trials Registry – In-
dia; Clinical Research
Information Service
– Republic of Korea;
German Clinical Tri-
als Register; Iranian
Registry of Clinical
Trials; Japan Primary
Registries Network;
Pan African Clinical
Trial Registry; Sri
Lanka Clinical Trials
Registry; The Nether-
lands National Trial
Register] All dates to
August 2013
TOTAL before removal of duplicates and first assessment 3398
TOTAL after removal of duplicates and first assessment 352
WHAT'S NEW
Date Event Description
14 April 2015 New search has been performed We performed a literature search update in November 2014. We
have put the search results into the Studies awaiting classifica-
tion section of this review. We will fully incorporate them into the
next review update.
14 April 2015 New citation required but conclusions We performed a literature search update in November 2014. We
have not changed have put the search results into the Studies awaiting classifica-
tion section of this review. We will fully incorporate them into the
next review update. The conclusions are unchanged.
HISTORY
Protocol first published: Issue 3, 2005
Review first published: Issue 2, 2008
Informed decisions.
Date Event Description
24 August 2013 New search has been performed A new update search was performed for this review on 24 August
2013
17 December 2008 New citation required but conclusions The update rendered one study (Oken 2006) which met the inclu-
have not changed sion criteria. The results of the review have slightly changed.
17 December 2008 Amended Incorporation of the risk of bias tables for all included studies
15 July 2008 New search has been performed A new update search was performed for this review on 15 July
2008
10 April 2008 New search has been performed The delayed memory functions data have been corrected
10 April 2008 New citation required and conclusions Errors in the data entry for the outcome delayed memory func-
have changed tion have been corrected. The effect of physical exercise on this
outcome are not statistically significant
CONTRIBUTIONS OF AUTHORS
JY and MA: drafted reviews, obtained copies of trial reports, selected trials for inclusion and exclusion, extracted and entered data, and
interpreted data analyses.
NT: screened trials for inclusion and exclusion, extracted data and interpreted data analyses.
JR: interpreted data analyses.
Consumer Editor: Judith Hoppesteyn-Armstrong
DECLARATIONS OF INTEREST
Jeremy Young - none known
Maaike Angevaren - none known
Jennifer Rusted - none known
Naji Tabet - none known
SOURCES OF SUPPORT
Internal sources
• No sources of support supplied
External sources
• NIHR, UK.
This update was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Dementia
and Cognitive Improvement group. The views and opinions expressed therein are those of the authors and do not necessarily reflect
those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health
INDEX TERMS
Medical Subject Headings (MeSH)

Cognition [*physiology]; Cognition Disorders [prevention & control]; Exercise [*physiology]; Memory [physiology]; Oxygen
Consumption [physiology]; Physical Fitness [*physiology]; Randomized Controlled Trials as Topic
MeSH check words

Aged; Humans; Middle Aged

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Cochrane

Aerobic exercise to improve cognitive function in older people

Young J, Angevaren M, Rusted J, Tabet N

Young J, Angevaren M, Rusted J, Tabet N.

Aerobic exercise to improve cognitive function in older people without

Jeremy Young1, Maaike Angevaren2, Jennifer Rusted1, Naji Tabet3

Editorial group: Cochrane Dementia and Cognitive Improvement Group.

Data collection and analysis

PLAIN LANGUAGE SUMMARY

BACKGROUND physical activity, cardiovascular fitness and cognitive function in

There was no difference in dropout rates between the aerobic

There was no difference in dropout rates between the aerobic

Wilbur 2005 {published data only} Angevaren 2007

References to studies awaiting assessment Christensen 1993

Aleman 2000 Cotman 2002

Cotman 2007 Hultsch 1999

Crooks 2008 Kessels 2000

Davenport 2012 Lachman 2010

Etgen 2010 Laurin 2001

Hultsch 1993 Middleton 2011

Newson 2006 Sturman 2005

Podewils 2005 Tierney 2010

Prins 2002 van Gelder 2004

Richards 2003 Verhaeghen 1997

Seeman 2001 WPP 2006

Characteristics of included studies [ordered by study ID]

Outcomes AI (Accuracy Index by finger movement)

Notes Testing took place at the University of Minnesota.

*THRR: (Karvonen) training HR = resting HR + [0.60-0.75 (HRR)].

Both groups showed slight increases in RPP from pre-test to post-test.

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No information provided.

Allocation concealment Unclear risk No information provided.

Bakken 2001 (Continued)

Selective reporting (re- Unclear risk Insufficient information.

Participants 101 participants aged 60 to 83 years

Outcomes Tapping (dominant/non-dominant)

Blumenthal 1989 (Continued)

Notes Testing took place at the Duke University Medical Center.

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No information provided.

Allocation concealment Unclear risk No information provided.

Participants 48 participants aged 61 to 86 years from a metropolitan inner-city community.

Emery 1990a (Continued)

Outcomes Digit Symbol substitution

Notes Testing took place at the Duke University Medical Center.

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No information provided.

Allocation concealment Unclear risk No information provided.

Selective reporting (re- Unclear risk Insufficient information provided.

Participants 32 participants in the age range of 60 to 76 years "from clubs".

Combined physical training and memory training.

Controls: no training whatsoever.

Outcomes Memory quotient (= total score of al WAIS subtests)

Notes Testing took place at the University of Montpellier.

Bias Authors' judgement Support for judgement

Random sequence genera- Unclear risk No information provided.

Allocation concealment Unclear risk No information provided.

Fabre 2002 (Continued)

Selective reporting (re- Unclear risk Insufficient information provided.

Follow-up period: 6 months.

Participants 124 participants aged 60 to 75 years of age.