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International Psychogeriatrics (2008), 20:1, 57–66 

C 2007 International Psychogeriatric Association


doi:10.1017/S104161020700631X Printed in the United Kingdom

MCI CONFERENCE PAPER

Cognitive training for persons with mild


cognitive impairment
..............................................................................................................................................................................................................................................................................

Sylvie Belleville
Research Center, Institut Universitaire de Gériatrie de Montréal, Canada

ABSTRACT

Recent randomized control trials and meta-analyses of experimental studies


indicate positive effects of non-pharmacological cognitive training on the
cognitive function of healthy older adults. Furthermore, a large-scale
randomized control trial with older adults, independent at entry, indicated
that training delayed their cognitive and functional decline over a five-year
follow-up. This supports cognitive training as a potentially efficient method to
postpone cognitive decline in persons with mild cognitive impairment (MCI).
Most of the research on the effect of cognitive training in MCI has reported
increased performance following training on objective measures of memory
whereas a minority reported no effect of training on objective cognitive measures.
Interestingly, some of the studies that reported a positive effect of cognitive
training in persons with MCI have observed large to moderate effect size.
However, all of these studies have limited power and few have used long-term
follow-ups or functional impact measures. Overall, this review highlights a need
for a well-controlled randomized trial to assess the efficacy of cognitive training
in MCI. It also raises a number of unresolved issues including proper outcome
measures, issues of generalization and choice of intervention format.

Key words: mild cognitive impairment, cognition, memory, cognitive training, cognitive intervention, memory
training

Introduction
There is increasing evidence for the role of environmental and lifestyle factors
as moderators of differences in cognitive aging and as protective agents for the
development of Alzheimer’s disease (AD) (Kramer et al., 2004). These factors
include education, engagement in professional and leisure activities, expertise
and experience. Given the involvement of such factors in the outcome of aging,

Correspondence should be addressed to: Sylvie Belleville, Research Center, Institut Universitaire de Gériatrie de Montréal,
4565 Queen Mary, Montreal, Québec, Canada. Phone: +1 514 340 3540 ext 4779; Fax number: +1 514-340-3548.
Email: Sylvie.belleville@umontreal.ca. Received 14 Feb 2007; revision requested 9 May 2007; revised version received
20 Aug 2007; accepted 21 Aug 2007. First published online 25 October 2007.

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it is reasonable to assume that cognitive training may play a critical role in the
promotion of cognitive vitality in normal aging and in AD. The provision of
cognitive training might also represent a powerful approach in persons with
mild cognitive impairment (MCI). These persons are at risk of developing AD
or other types of dementia since older persons meeting criteria for MCI have
a more frequent progression rate to AD than those not meeting MCI criteria
(e.g. Geslani et al., 2005). Persons with MCI retain a large range of cognitive
capacities which make them an ideal target for cognitive training. The concept of
MCI has spurred a great deal of scientific effort, particularly for the identification
of proper clinical and neurobiological criteria. Research studies have also been
conducted in the domain of pharmacological or non-pharmacological cognitive
interventions. Given the potential for cognitive training as a way to delay cognitive
decline in older adults, an overview of the state of the literature on the topic is
timely.
The goal of this paper is to provide a literature review and assess the empirical
data regarding the role of non-pharmacological training approaches to MCI
while focusing, in particular, on cognitive intervention. The review relied on
a literature search using medline and Psycinfo with “cognitive training” and
“MCI” or “memory training” and “MCI” as key words. This paper begins with
a general description of the concepts related to cognitive intervention and then
summarizes relevant data published on healthy older adults. Finally, it presents
studies using MCI.

The different forms of cognitive intervention used in older adults


In a recent review of the literature on intervention and dementia, Clare et al.
(2005) identified three approaches to cognitive intervention. Cognitive
stimulation refers to the involvement in group activities that are designed
to increase cognitive and social functioning in a non-specific manner. Those
include discussions, supervised leisure activities, list memorization with no
particular support and more structured activities such as reality orientation or
reminiscence. Cognitive rehabilitation involves individually tailored programs
centered on specific activities of daily life (e.g. learning the name of
a new caregiver). Finally, cognitive training involves teaching theoretically
motivated strategies and skills in order to optimize cognition functioning (e.g.
mnemotechnics). Cognitive training is most often provided in small groups and
in a standardized fashion.
The focus in the present paper is on cognitive training since its efficacy in MCI
has been the most often tested. Cognitive training includes repeated problems
and exercises that are designed to work out and drill impaired cognitive capacities
under different conditions. This approach is most often used for improving
elementary domains of cognition such as speed of processing, useful field of
view and attention. Cognitive training also involves teaching strategies that
exploit spared cognitive capacities to improve impaired ones. For example, some
memory-training techniques rely on visual imagery to support episodic memory.
Other techniques involve the acquisition of strategies that optimize cognition,
Cognitive training and MCI 59

such as spaced retrieval or self-cuing memory optimization strategies. Cognitive


training can also result in improving meta-cognition (i.e. the knowledge that
participants have about memory mechanisms and their own memory), and
cognitive self-efficacy (i.e. the notion that participants can exert some control
over their cognition). Importantly, cognitive training does not correspond to
non-specific “brain jogging.” Proper cognitive training programs must rely on
theoretically valid training techniques that take into account the pattern of
impaired and intact capacities. Although this is not always done, these programs
should ideally address the question of ecological validity and consider the impact
of the intervention on a participant’s well-being and response to real life activities.
Finally, these programs ought to rely on techniques that have received empirical
support.
Most studies assessing the efficacy of cognitive intervention in healthy older
adults have relied on cognitive training programs (e.g. Yesavage et al., 1990;
Stigsdotter and Bäckman, 1995; Ball et al., 2002). Verhaeghen et al. (1992)
performed a meta-analysis on 33 studies of memory training involving a total
sample of 1539 normal older adults. The analysis revealed a large effect size for
the training effect (about 0.7). Training was more effective when conducted in
short sessions, with small groups and when accompanied by pre-training on non-
memory components (e.g. improving visual imagery or reducing stress). In terms
of the participants’ characteristics, higher mental status (typically measured
with the MMSE) and younger age were positively correlated with cognitive
training efficacy (Verhaeghen et al., 1992). In a large clinical trial involving
2802 older American seniors, the ACTIVE study indicated that training on
memory, problem solving and useful field of view in normal aging yielded an
enduring improvement on target cognitive domains. The improvement observed
was equivalent to a 7–14 year reduction of aging effects (Ball et al., 2002) and
the positive effect was still observed after a five-year follow-up (Willis et al.,
2006). No significant impact was found on functional activities on a two-year
follow-up. This was probably due to the high level of functioning of the healthy
older adults enrolled in the study as no functional decline was apparent over
the two-year follow-up. In a five-year follow-up, the team reported significant
functional decline in all participants. The decline was not as marked in those
who were part of the training groups, an effect that was significant in the group
that received training on problem solving (Willis et al., 2006).

Empirical support for cognitive intervention in MCI


The finding that cognitive training can delay cognitive and functional decline in
healthy older adults has tremendous consequences for its potential application
to MCI. Cognitive intervention may benefit persons with MCI because these
individuals have a high need for treatment and they retain the cognitive
capabilities to learn and apply sets of new strategies. If designed properly,
cognitive intervention could optimize the cognitive functioning of persons with
MCI, reduce their handicap and alleviate the anxiety resulting from their
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cognitive difficulties and failures. Thus, efficient intervention programs could


yield paramount benefits in terms of cognitive capacities and quality of life.
There has been some debate as to which approach – cognitive stimulation,
cognitive training or cognitive rehabilitation – should be favored in persons
with MCI. This has been raised as an issue because cognitive training has
not received compelling support when used in demented patients (Clare et al.,
2005). Thus, a number of authors have proposed that cognitive rehabilitation
may be a more adapted approach for persons with dementia because it can be
adapted to the pattern of impairment of individual patients (e.g. Adam et al.,
2000; Lekeu et al., 2002). It has been suggested that a similar individually
based rehabilitation approach might be used in persons with MCI (e.g. Van der
Linden et al., 1994). One drawback is related to the fact that persons with MCI
experience little functional impact on daily activities, these activities being the
typical focus of rehabilitation. Identifying activities that would be proper targets
for cognitive rehabilitation in MCI may thus represent a challenge and reduce
the cost-efficacy ratio of this particular approach in this population of older
adults. This may be the reason why, to our knowledge, all intervention studies
published so far in MCI have relied on a cognitive training approach.
Based on our literature search, seven published studies have investigated
the impact of cognitive intervention in persons with MCI. Rapp et al. (2002)
compared a memory intervention condition to a no-training condition in persons
with MCI. The program involved six weekly sessions: one that provided general
information regarding dementia and memory, and five devoted to teaching
specific memory skills (e.g. cueing, categorization). MCI participants were
recruited from the community. They had memory deficit with no other cognitive
impairment, thus meeting criteria for amnestic MCI single domain (Petersen
and Morris, 2005). The participants’ perception of their memory capabilities
(subjective memory measures) was improved following training, but no effect
was found on objective memory measures. However, their study included a very
small number of fairly old participants (nine participants in each group were
on average 75 years of age). Furthermore, their intervention was not optimal.
It included few sessions, each session being very long and there was no pre-
training on visual imagery in spite of the fact that this is likely to be fundamental
to the appropriate use of efficient imagery-based memory strategies (Brooks
et al., 1999).
Günther et al. (2003) tested a computer-assisted cognitive training program in
19 older persons with MCI. The participants were recruited from a residential
home for older people. They had a memory complaint and performed 1 SD
below normative values. The program involved 14 training sessions and the
effect of the training program was tested immediately after completion and
five months later. The authors reported positive training effects on objective
measures of episodic and working memory, but not on subjective measures of
cognition. Furthermore, the positive effect was maintained over the long term.
However, their study is limited by the fact that they did not include a group with
no intervention to test for repetition effects on the cognitive outcome measures.
Recently, three related studies were published on the efficacy of a computer
intervention program in persons meeting criteria for amnestic MCI (Cipriani
Cognitive training and MCI 61

et al., 2006, Rozzini et al., 2007; Talassi et al., 2007). Their program involved
exercises covering a broad range of cognitive capacities including memory,
attention, perception and language. In one of those studies (Rozzini et al.,
2007), the authors reported enduring effect in a one-year randomized study
that compared 59 MCI patients receiving pharmacological therapy (ChEIs)
and cognitive training, pharmacological therapy only, or neither. The training
program was applied in three blocks of 20 one-hour sessions. The group treated
with pharmacological therapy and cognitive training improved their scores on
memory and problem solving tasks as well as on the neuropsychiatric inventory.
Performance on the geriatric depression scale was improved in both those treated
with pharmacological therapy and those treated with pharmacological therapy
and cognitive training.
A study by Olazaran et al. (2004) reported positive effects of cognitive
intervention in 72 people with AD and 12 persons with MCI. Participants
were recruited from clinical units, and persons were identified as MCI on the
basis of Flicker’s criteria (equivalent to a GDS of 3; Flicker et al., 1991). All
patients attended a day hospital. Untreated patients attended the psychosocial
program usually provided by the day hospital. Treated participants were enrolled
in different cognitively demanding activities including list memorization during
a one-year period. Thus, the intervention corresponds more to the definition
of cognitive stimulation than to the definition of cognitive training because,
contrary to the other studies cited here, enrolled patients did not receive training
with particular memory strategies such as organization or mental imagery but
completed informal cognitive activities. The study reported both an increase in
cognition and a decrease in cognitive symptoms in those patients enrolled in the
cognitive stimulation program relative to patients who attended the psychosocial
program usually provided by the day hospital. Note, however, that as the authors
did not analyze the data from those people with MCI separately from those of
migraine with aura (MA) patients, it is unclear whether the former – a relatively
small proportion of the whole group – were actually responsive to cognitive
stimulation. It is indeed possible that providing only non-specific cognitive
activities is insufficient to improve the performance of persons suffering from
relatively mild cognitive impairment.
Belleville et al. (2006) developed a multi-factorial intervention program
tailored to the needs of persons with MCI. The program was designed to
improve episodic memory, a component that is shown to be impaired in MCI,
by providing teaching on a number of episodic memory encoding strategies
that rely on visual imagery, semantic knowledge and organization. The program
also included pre-training in executive control (Kramer et al., 1995), cognitive
speed (Baron and Mattila, 1989) and visual imagery. Furthermore, the program
included instruction on relaxation and on the impact of aging on cognition. A
number of elements were implemented in the program to increase generalization,
such as exercises with graded levels of difficulty, homework and specific
instructions on how to use the strategies in real-life situations. Participants
were invited to take part in eight weekly group sessions (each with four to
five participants) and they were tested with objective and subjective memory
measures one week prior to and one week after the intervention.
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The study included 21 participants with MCI who took part in the training
and eight participants with MCI who were included in a no-intervention control
group. Groups of treated and untreated healthy older adults were also included in
the program. The study reported a significant positive effect of the intervention
on objective measures of episodic memory (delayed recall of word lists; face name
association) in both healthy older adults and persons with MCI. Effects sizes for
these intervention effects were large to medium. There was also a significant
training effect on a subjective memory measure (memory questionnaire) and on
well-being. In contrast, none of these measures improved in the no-intervention
group. Younger age and a higher level of education were associated with larger
training effects. However, severity of the memory deficit (as measured by story
recall) or of the global cognitive deficit (as measured by MMSE and Mattis
dementia rating scale; Mattis, 1976) was not related to training efficacy. Thus,
the success of the intervention is related to pre-morbid personal variables and is
unrelated to the extent of impairment within the group of people with MCI.
Interestingly, memory training has been associated with neurobiological
changes. Valenzuela et al. (2003) measured the effect of the method of loci, a
memory training technique that supports list memory through the use of visual
imagery, in healthy older adults. They used magnetic resonance spectroscopy
to measure brain neurochemistry in different brain regions. Following training,
memory improved and this was associated with an increase in the choline and
creatine signals in the hippocampus. Nyberg and collaborators (2003) measured
brain activation with positron emission tomography (PET) in healthy older
adults who were trained to use the loci method. They reported that older adults
who succeeded in using the technique showed increased activation in parieto-
occipital areas. Similar results have been found by Belleville et al. (2007) in a
group of older persons with MCI using functional magnetic resonance imaging
(fMRI). Following memory training, the people with MCI showed increased
brain activation in parietal areas and a slight increase in the activation of frontal
areas. Using evoked related potentials measures, the authors also found increased
amplitudes of the P2 component, a brain wave that has been related to the active
retrieval of information.

Conclusion
The role that cognitive training has been shown to play in the cognitive vitality of
healthy older adults suggests that cognitive training may also serve to optimize
the cognitive functioning of persons with MCI and perhaps contribute to a
slowing of cognitive decline and the onset of disability. In recent years, there has
been an increasing number of studies assessing the effect of cognitive training
in MCI. Those studies have indicated that such training may have beneficial
effects on objective experimental cognitive measures. While one study failed to
report any positive effect on objective measures, six studies have reported positive
findings – that is, improvement of performance following training. Obviously,
there is an important opportunity for clinical trial development in the field of
Cognitive training and MCI 63

non-pharmacological or cognitive training considering the large effect sizes


reported in preliminary studies.
However, a large number of uncertainties still exist regarding the role and
efficacy of cognitive interventions for people with MCI, and additional research
is necessary for a number of reasons. One major issue is the need for studies
that use larger samples of participants and randomized controlled designs. The
MCI population is heterogeneous and not everyone with MCI will progress to
dementia. This heterogeneity increases the importance of relying on relatively
large sample size studies.
The identification of proper outcome measure will be critical. Most non-
pharmacological studies of MCI have used cognitive symptoms as their endpoint.
Yet, conversion to dementia may be viewed as a more appropriate endpoint.
Note, however, that this in itself may turn out to be problematic because
conversion is a strictly binary outcome and needs to be based on stringent
and valid criteria. Thus, any variant in the criteria used to define conversion is
likely to impact quite significantly on the conclusions derived at in the study.
Considering that MCI and dementia are now seen as a continuum, there may
be an advantage in using symptom progression as a useful outcome – but, here
again, the manner in which progression is measured and defined will need to be
established.
The question of functional outcomes is another unresolved issue raised in
treatment studies. Functional measures are important both because they are key
in the definition of dementia and because their sensitivity to treatment provides
valid observable endings. Yet, we need to measure functional effects of treatment
on measures that are sensitive to MCI and sensitive to the training provided.
Generalization effects to subjective measures in some of the studies suggest
that the intervention has ecological validity. However, this needs to be measured
directly using tools that are more commensurate with real-life situations.
Resolving the issue of functional impact may bear some relevance with the
notion of generalization. In addition, researchers need to document the long-
term efficacy of interventions in MCI and their impact on conversion to
dementia. Long-term studies of healthy older adults suggest that the positive
effect of training is enduring. However, this may not be the case in a population
experiencing cognitive decline, such as people with MCI. Introducing booster
sessions, that is, sessions in which the strategies are later reviewed with
participants, may increase the long-term maintenance of cognitive training. Just
like physical fitness training, it is possible that maintenance of the positive effect
of cognitive training depends on the reinstatement of the original instruction in
the form of booster sessions. There is also a need to test whether an individually
tailored approach – in which the intervention is adapted to individual patients
(Van der Linden et al., 2004) – is more valuable in MCI than the small-group
standardized approach. Cognitive interventions may also be most favorably
combined with interventions that address psychosocial, attribution or self-
regulatory factors (e.g. West and Yassuda, 2004). Designing interventions that
predominantly address executive controls may also be appropriate for persons
with MCI, as it has been shown that executive control is impaired in this
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population (e.g. Belleville et al., 2002; 2007). Along these lines, it is important to
determine the combined value of cognitive and pharmacological interventions
for improving the cognition and well-being of persons with MCI. Indeed, it
has been suggested that combining the two approaches is optimal in dementia
(Requena et al., 2004) and it may also be the case in MCI (Rozzini et al.,
2007).
Finally, memory training in older healthy persons has been associated with
changes in brain activity and neurochemistry (Nyberg et al., 2003; Valenzuela
et al., 2003; Belleville et al., 2007). As research unravels the extent of cognitive
malleability in aging and early dementia, it will be essential to investigate how
neural plasticity is implemented in the brains of affected individuals.

Conflict of interest
None.

Acknowledgments
Sylvie Belleville is supported by a research investigator national award from the
FRSQ and receives grants from the CIHR, CONCOV-Valorisation Recherche
Québec, NSERC and REPAR-FRSQ network. The author is grateful to Harold
Gaboury for editorial assistance and Marc-Antoine Labelle for help in preparing
the manuscript.

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