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For personal use. Only reproduce with permission The Lancet Publishing Group.
THE LANCET
NeurologyVol 3 June 2004 http://neurology.thelancet.com
343
The recent availability of longitudinal data on the possibleassociation of different lifestyles with dementia and Alzheimer’s disease (AD) allow some preliminaryconclusions on this topic. This reviewsystematicallyanalyses the published longitudinal studies exploring theeffect of social network, physical leisure, and non-physicalactivity on cognition and dementia and then summarisesthe current evidence taking into account the limitations ofthe studies and the biological plausibility. For all threelifestyle components (social, mental, and physical), abeneficial effect on cognition and a protective effectagainst dementia are suggested. The three componentsseem to have common pathways, rather than specificmechanisms, which might converge within three majoraetiological hypotheses for dementia and AD: thecognitive reserve hypothesis, the vascular hypothesis, andthe stress hypothesis. Taking into account theaccumulated evidence and the biological plausibility ofthese hypotheses, we conclude that an active and sociallyintegrated lifestyle in late life protects against dementiaand AD. Further research is necessary to better define themechanisms of these associations and better delineatepreventive and therapeutic strategies.
Lancet Neurol
2004;
3:
343–53
It is a common belief that maintenance of an active life helpsold people to preserve their physical and mental health.Many clinicians have observed that an old patient’s capacity to cope with disease can be negatively affected by unfamiliarenvironments, such as hospitals. For decades psychologistshave studied the effect of an engaged lifestyle on cognitivedecline,
1
and developed the disuse hypothesis.
2
Sociologistshave examined the effect of social network on cognitiveability and suggested that social isolation acceleratescognitive decline in ageing.
3
In addition, many studies haveshown that social network, leisure activities, and physicalexercise prolong life, improve physical health in general, anddecrease the occurrence of specific diseases such ascardiovascular disease.This background has led to the hypothesis that bothsocial network and leisure activity are implicated in thedevelopment of dementia and Alzheimer’s disease (AD).During the past 5 years, sufficient results from longitudinalstudies have been published to allow some conclusions to bemade. This reviewassesses the published longitudinalstudies of lifestyles and cognition and dementia, andsummarises the current evidence, taking into account thelimitations of the studies and biological plausibility.
Lifestyle effects on survival and health
There is a large amount of epidemiological data on thehealth benefits of social integration and social support. Andthere is more evidence of the effects of leisure activities onhealth and survival, especially physical activities and physicalexercise.
Social networks
In a review paper, House and colleagues
4
concluded thateven after controlling for baseline health status, people withboth a small quantity and a low quality of social relationshave an increased risk of death. In a comprehensive reviewon the effects of social environment on health and ageing,Seeman and Crimmins
5
more recently stated that there isclear evidence for the hypothesis of a generally health-promoting effect of social relationships. The beneficial effectseems to be widespread and life-long from childhood tomiddle and old age. The evidence is mainly from studieswith mortality as the outcome.
6–8
Overall, socially isolatedpeople have two to four times increased risk of all-causemortality compared with those with extended ties to friendsand relatives and in the community.
6,9
In addition, withphysical function as an indicator of general health status,several studies have reported an association between limitedsocial ties and physical decline.
10
The effects of social network on morbidity have mostcommonly been studied in relation to cardiovasculardisease, especially coronary heart disease (CHD) andstroke.
11–14
Authors of a systematic review of psychosocialfactors in the aetiology and prognosis of CHD concludedthat prospective cohort studies provide strong evidence of an independent aetiological and prognostic role of socialsupport for CHD.
12
According to Berkman and colleagues
15
and Seeman,
16
emotional support could have a major role indetermining a favourable prognosis after CHD and stroke.
 Leisure activity 
Survival is the most common measure of benefits from non-physical activity. In a Swedish study in 1996, peopleattending cultural events, reading books or periodicals, and
Review
Lifestyle and dementia
 All authors are at the Aging Research Center, Division of GeriatricEpidemiology and Medicine, Neurotec Department, KarolinskaInstitute and Stockholm Gerontology Research Center, Stockholm,Sweden.
Correspondence:
Prof Laura Fratiglioni, Aging Research Center,Olivecronas väg 4 (Box 6401), S-113 82 Stockholm, Sweden.Tel +46 8 6905818; fax +46 8 6905954;email laura.fratiglioni@neurotec.ki.se
 An active and socially integrated lifestyle in latelife might protect against dementia
Laura Fratiglioni, Stephanie Paillard-Borg, and Bengt Winblad
 
For personal use. Only reproduce with permission The Lancet Publishing Group.
THE LANCET
NeurologyVol 3 June 2004 http://neurology.thelancet.com
344
playing music or singing in a choir survived longer thanthose who did not participate in such activities;
17
a similarpositive effect was observed in a US study, in which survivalwas longer in people participating in social and productiveactivities.
18
This beneficial effect was similar to andindependent of the effect of fitness activity, which suggeststhat mechanisms other than increased cardiopulmonary fitness might be involved. Similar results have been reportedmore recently from another Swedish study, where greatersurvival was detected in people engaged in solitary activity,such as reading of books or newspapers or solving of crossword puzzles.
19
 Physical activity 
By 1995 the American Centers for Disease Control andPrevention and the American College of Sports Medicinealready encouraged US adults to have 30 min or more of moderate-intensity physical activity on most, preferably all,days of the week.
20
This recommendation was on the basisof an extensive review of research on mortality in generaland cardiovascular disease in particular. Physical activity decreases the risk of cardiovascular disease and improvessurvival after a cardiovascular event.
21
This positive effecthas been shown in men and women
22,23
as well as in middleage and old age.
24
Light to moderate exercise can have asimilar beneficial effect to vigorous physical activity.
25–27
The evidence for a protective effect against stroke is lessstrong.
21
Beneficial effects of physical exercise have beenreported in several diseases—such as hypertension,diabetes mellitus, obesity, osteoporosis, anddepression.
21,28–30
Lifestyle effects on cognition
Research on different lifestyles and cognition is importantfor understanding and better defining their possible effectson dementia. We present here a systematic review of theobservational studies and a summary of the randomisedclinical trials.
Observational studies
Several cross-sectional studies have showed that cognitiveability is strongly related to social ties and various activities.These studies were excluded because of the lack of correcttemporal relation between cause and effect.
Review
Lifestyle and dementia
Table 1. Observational longitudinal studies of the association between social network and cognition
Study, RefnAge at Social Follow-upCognitive Control ReportedCountrybaseline networks (years)assessmentfactorsassociations(years)at baseline
Bassuk et al,312812>65Social engagement index 3, 6, 12 Global cognitive Eth, Inc, Social disengagementUSA(marital status, contacts, functioning (Short PMF, Depr, with cognitive declineattendance of church, Portable Mental Status CVD, Smok,recreational activities)Questionnaire)Alc, PA, ESHultsch et al,32250 5865Social activities; new-6 Decline in cognitive CD, IADL, No association of socialCanadainformation-processing functioning (memory, SH, Med, activities with cognitionactivities; physical activitycomprehension, andspeed)PersSeeman et al,331189 70–79Social ties; emotional 5 Neuropsychological Eth, Inc, CD, Emotional support (butUSAsupport; instrumental supportbattery (language, Dep, SEB, not social ties) withmemory, PAbetter cognitive functionconceptualisation,visuospatial ability)Bosma et al,348304981Physical exercise, mental 3 Specific tests for CogLow participation in anyNetherlandsand social activities memory, verbal fluency;activity with cognitiveglobal cognitive test decline(MMSE) Aartsen et al,352076 5585Everyday activity, including 6Specific tests for PFNo association of anyNetherlandssocial, experiential, and memory, fluid activity with cognition,developmental activitiesintelligence, and speed, but information-global cognitive test processing speed with(MMSE)developmental activityMenec, 361292 67–95Social, mental, and 6Combined physical and ADL, IADL, Greater overall activity,Canadaproductive activities; number mental function indexCog, SH, and social andof leisure activitiesMorb, LS productive activities withbetter functionZunzunegui 37 964 >65Social relations (social 4Global cognitive Dep, BP, PFPoor social relations, lowet al,Spainnetwork, social integration, functioning (scale participation in socialand social engagement)including memory and activities, and socialorientation items)disengagement withcognitive decline
 All associations were controlled for age, gender, and education. Eth=ethnicity; Inc=income; CVD= cardiovascular disease; PMF=physical and mental function; dep=depression;smok=smoking; alc=alcohol; PA=physical acivities; ES=emotional support; CD=chronic diseases; IADL=instrumental activity daily living; SH= subjective health; med= medication;pers=personality; SEB=self-efficacy believe; cog= cognitive function; PF= physical function; morb=morbidity; LS=life satisfaction; BP=blood pressure.
 
For personal use. Only reproduce with permission The Lancet Publishing Group.
THE LANCET
NeurologyVol 3 June 2004 http://neurology.thelancet.com
345
We identified 15 observational longitudinal studies,which were all done in Europe and in North America,
31–44
except one from China (tables 1–3).
45
With the exception of two investigations that included a large sample of volunteers,
32,38
all are population-based studies from wellknown cohort surveys focused on ageing. The initial cohortof the MacArthur Studies of Successful Aging comprisedhigh-functioning older adults, which could limit thegeneralisability of the findings.
33,41
The definition of different activities and social networkvaries largely not only in the measurements used but also inthe conceptual level of investigation. Some studies usedsimple quantitative assessment, such as number of socialties, number of activities, and time devoted to activities.Other studies took into account underlying dimensions andpossible mechanisms by examining emotional or structuralsupport, social integration, and social engagement; newinformation processing activities, cognitive activity score,experiential activities, and developmental activities; orspecific aerobic exercises. With the available information, itis not possible to identify the effect of a specific mental orphysical activity; therefore, generalisations are made aboutbroad categories. Large variation is also present in theassessment of cognitive performance, ranging from very short global cognitive tests
31
to large neuropsychologicalbatteries testing multiple cognitive domains.
32,33
Most of thestudies examined the association between the lifestyleassessed at baseline and cognitive performance at follow-up;only six studies related the lifestyle to cognitive decline. Lessvariation is present in the length of follow-up (6–7 years inmost studies). Only one study had a follow-up of less than3years,
41
and one study examined results derived from threefollow-ups expanding the observational period to 12 years.In only two studies did researchers assess midlife activity inrelation to cognitive ability after 65 years of age.
38,40
All studies controlled for demographics includingeducation, but only a few included other indicators of socioeconomic status, which could have a confounding role.Whether education sufficiently controls for the socioeconomicstatus is unclear, especially in these elderly cohorts where socialmobility was common.
46
All studies controlled for baselinecognitive performance and for health status, mostly measuredwith functional scales or self-assessment or reported diseases.Few studies explicitly controlled for depression,
31,33,37,44
and only two for personality.
32,38
As commonly happens in epidemiological research, noneof the reported studies were totally free of methodologicalproblems. Although each study has some limitations, theresearchers consistently tried to verify the possible effect of such limitations on their results. In summary, the findingsfrom these studies can be regarded as internally valid.
 Randomised controlled trials
There are no randomised controlled trials that test thehypothesis that a rich social network decreases age-relatedcognitive decline.
Cognitive training
Numerous cognitive training interventions have been doneunder laboratory or small-scale clinical conditions. In general,
Review
Lifestyle and dementia
Table 2. Observational longitudinal studies of the association between non-physical leisure activities and cognition
Study, RefnAge at Non-physical activitiesFollow-upCognitive Control ReportedCountrybaseline (years)assessmentfactorsassociations(years)
Gold et al,38 316 64·7 Engaged lifestyle (SES, locus 40Intelligence (verbal, SRH, pers, Engaged lifestyle withCanada
*
men(mean atof control and intellectual nonverbal, mechanical paternal SESmaintenance of verbalfollow-up)activities)tasks)intelligenceHultsch 322505586Social activities; new-6Decline in cognitive CD, IADL, Intellectually challenginget al, information-processing function (memory, SH, med, activities with lower probabilityCanadaactivities; physical activitycomprehension, and speed)persof cognitive decline, but alsohigher cognition with higheractivityBosma 348304981Physical exercise, mental, and 3Specific tests for memory, CogAll three activities with loweret al,social activities (hours per and verbal fluency; global probability of cognitiveNetherlandsweek)cognitive test (MMSE)decline, but also highercognition with higher activity Aartsen 3520765585Everyday activity, including 6Specific tests for memory, PFNo association of any activityet al,social, experiential, and fluid intelligence, and speed;with cognition, but information-Netherlandsdevelopmental activitiesglobal cognitive test (MMSE)processing speed withdevelopmental activityMenec,36 129267–95Social, mental, and productive6Combined physical and ADL, IADL, Greater overall activity, andCanadaactivities; number of leisure mental function indexcog, SH, social and productiveactivitiesmorb, LSactivities with better functionRichards 39191936Spare-time activity (activities 7Verbal memorySES, IQ, SH, Spare-time activity andet al,with high social and mental depphysical exercise with betterUKcomponent); physical exercise memory performance in midlife
 All associations were controlled for age, gender, and education. SES=socioeconomic status. Additional control was performed for SRH=self reported health; pers=personality;CD=chronic diseases; IADL=instrumental activity daily living; SH=subjective health; med=drug use; cog=cognitive function; PF=physical function; morb=morbidity, LS=lifesatisfaction; dep=depression.
*
Confirmed by Arbuckle et al (reference 40) with a follow-up of 45 years.
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