EEE Physical Activity and Risk of Cognitive Impairment and Dementia in Elderly Persons Danielle Laurin, MSc; René Verreault, MD, PRD; Joan Lindsay Kathleen MacPherson, MD: Kenneth Rockwood, MD Context: Dementia is common, costly, and highly age related. Little attention has been paid to the identifica- tion of modifiable lifestyle habits for its prevention, Objectives To explore the association between physi- cal activity and the risk of cognitive impairment and dementia, Design, Setting, and Subjects: Data come from a community sample of 9008 randomly selected men and women 65 years or older, who were evaluated in the 1991-1992 Canadian Study of Health and Aging, 44 prospective cohort study of dementia, OF the 6434 cligible subjects who were cognitively normal at baseline, 4615 completed a 5-year follow-up. Sereen- ing and clinical evaluations were done at both waves of the study. In 1999-1997, 3804 remained without ‘cognitive impairment, 436 were diagnosed as having, cognilive impairment-no dementia, and 285 were diagnosed as having dementia. PhD; Main Outcome Measure: Incident cognitive impairment and dementia by levels of physical activity at baseline Results: Compared with no exercise, physical activity was associated with lower risks of cognitive impair- ment, Alzheimer disease, and dementia of any type. Sig- nificant trends for increased protection with greater physi- cal activity were observed. High levels of physical activi were associated with reduced risks of cognitive impair- ment (age-,sex-,and education-adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.83), Alzheimer disease (odds ratio, 0.50; 95% confidence interval, 0.28-0.90), and dementia of any type (odds ratio, 0.03; 95% confi- dence interval, 0.40-0.98), Conclusion: Regular physical activity could represent aan important and potent protective factor for cognitive decline and dementia in elderly persons. Arch Neurol, 2001;58:498-504 From the Laval University Geriatric Research Uni, Centre Phcbergement St-Augustin da ‘Centre hospitaler afi universtave de Quebec EMENTIA represents a ‘major health problem in aging societies." Apart from hormonal replac ‘ment therapy"? and ant settings, beneficial effects of physical fi ness interventions on memory and other aspects of cognition have been docu- ‘mented in elderly persons, although in- consistently.2»>* Beauport, and Department of ‘Social and Preventive Medicing Laval University, Sainte-Foy Quebec (Ms Laurin and Dr Verveault); Department of Epidemiology an Community ‘Medicine, University of Ottawa, ‘Ottawa, Ontario, and Aging Related Diseases Division, Laboratory Center {for Disease Control, Health ‘Canada, Ottawa (Dr Lindsay) cand Department of Community Health and Epidemiology Dalhousie University, Half, [Nova Scotia, and Division of Geriatric Medicine, Dalhousie University, Queen Elizabeth Health Sciences Center Halifax (Drs MacPherson and Rockwood) hypertensive'® and nonsteroidal anti- inflammatory drug* treatments, few preventive strategies for dementia and its leading cause, Alzheimer disease, have been explored "* Comparatively litle at- tention has been paid to the identifica tion of modifiable environmental factors such as diet and lifestyle habits, snclud- sng physical fitness Physical activity has well-known ben- clits for several chronic disorders," in- cluding coronary arte diabetes melitus, and osteoporosis. While its influence on premature mortality mong both young and old segments ofthe elderly population is also well estab- lished,* the evidence that physteal ac- tivity may delay cognitive loss and impale rent is more equivocal" Im clinical disease, stroke, (©2001 American Med jamanetwork.comy/ on 01/24/2021 Few epidemiological studies have ex amined the role of physical activity on the risk of cognitive impairment and demen- tia in elderly persons, Suggestions that ex- ercise may be protective for dementia, and for Alzheimer disease in particular, have been made in some case-control studies us- ing prevalent cases,” but again these findings have not consistently been rep- licated.*"” In these studies, retrospective ‘of physical activity anits the validity of the results. Discordant results have also been reported in a few prospec- tive studies. This study evaluates the association between regular physical activity and sub- sequent occurrence of cognitive impair- ‘ment and dementia, within the Canadian Study of Health and Aging (CSHA),alarge- Association, All rights reserved.SUBJECTS AND METHODS Data come from the community sample of the CSHA. a na- ‘ional, multicenter, prospective cohort study, designed tof ceuson the prevalence, incidence, and risk faciorsfor demen- ‘sand Alzheimer dseasein elderly Canadians. Methodological details ofthe study have been described elsewhere**” Briefly, ‘daring the fist wave ofthe study conducted in 1991-1002 (SHAD, representative samples of men and women 65 years or older were drawn from population-based listings for 36 ‘whan and surrounding rural areas inal 10 Canadian prov- {nces, Of the 10263 people involved, 9008 were living inthe community and constituted tr initial pool of subjects. ll ‘subjects were interviewed to ascertain thie perceived health status, general chronic conditions, and functional ability in basic and instrimental activities of daily living, based on 3 ‘modified version of the Oder Americans Research Survey scale." Participants were sereened for dementia using the Modified Mini-Mental State (3M) Examination." Sub- ects who sereened positive (3MS Examination sore $77), anda random sample of those who screened negative (MS Examination score =78) were asked to atend an extensive standardized sage clinical evaluation.” A nrsefirst screened for hearing and vision problems, and collected information bout medication regimen and medical ana family histories, ‘Next, a physician caried out standardized physical and new- rologic examinations, Third, a psychometrst administered aneutopsychological test battery” toall individuals deemed, testable (MS Examination score =50), the results of which, were interpreted by a neuropsychologit. Preliminary diag- noses were made independently according to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteri” by the physician andthe neuropsychologit who sab> sequen arrived at a diagnosis in a consensus conference Consensts diagnoses constituted the following: no cogni {ive impairment, cognitive impsirment-no dementia [CIND]™ Alzheimer disease (probable or possible) according to NINCDS-ADRDA (National Institut of Neurological Disor- ders and Stroke-Alzheimer’s Disease and Related Disorders Assocation) criteria, vascular dementia according to World Health Organization International Classification of Disease, 10th Revision erteria* other specific dementia and unclas” siabl dementia. ll subjects without dementia were asked to-complete and return by mallaselladministered ik fac torquetionnsre covering peciicexposons or which prior hypotheses existed. This questionnaire included ques- {None about demographic characterises, occupational and environmental exposures, ifesyle, and medial and fm- iy histones Follow-up wascarred out in 1999-1997 (CSHA-2). All subjects who could be contacted and who aged to partic Pate inthe second wave were relnterviewed to measure hangesin health stat and functioning following 35-year riod om average Subjects took pat tn the sme dlagnos- Uc proces a in CSHA"1, including screening and ciel evaluation, Diagnose from consensus conferencsin CSHA-2 swore made without knowledge of SHA diagnoses, Two Tal diagnoses were made for dementia and vascular de- tmenta, one according tothe same criteria used in CSHA-1 andthe other according vo more recent Diagnostic and Sia tistical Manual of Mental Disorders, Fourth Edition” and NINDS-AIREN (National Insitute of Neurlogieal Disor ders and Siroke-Association Internationale pour la Re- cherche et TEnsegnement en Neurosciences) eel” Exercise data were cllcied a part of CSHA-1 when subjects were not demented and represen a proxy fr ear ier activity up unl the ime of basclne. The level of physi cal activity wae asesed by combining > questions from the fek actor questionnate regarding Irequency and intensity Of exerts for subjects who reported regular physical act fy. A compost score ling physical activity as ether lov, ‘moderator high, was cbianed by summing answers tothe frequency question (3 times per week, weekly, ores than ‘wee andthe intensity question (moe vigorous equal, Oo les vigorous than walking) high level of physical a {ity corresponded toan exercise engaged 3 or more times er weekal an intensity greater than walking, while a rod rate level of plyscal activity coresponded to exercise also engaged 3 or more mes pr week but ofan intensity equal towalking all other combinations of quency and inen- sy were considered as low level of physical sci. Sub- jects wo repored no regular exercise constituted the reer- ce category. The measurement properties of hs index were Continued on next page scale, prospective cohort study, based on a representa live sample of the elderly Canadian population, (as Unimpaired subjects were younger and had completed more Years of education (medians of 72 and 11 years, re spectively) than those with CIND (medians of 78 and © years) or dementia (medians of 80 and 10 years) (Fale 1). The sex distribution was similar across categories, Re- ported regular exercise was more frequent for controls than for subjects with CIND or dementia. Table | also lists the distribution of these characteristics for eligible subjects in CSHA-1 who died during follow-up or did not partic pe in CSHA-2, Decedents and nonrespondents were older, less educated, and less physically active at baseline than subjects in the control group, and were generally similar to the group of subjects with CIND or dementia, (aernoytep) ARCH NETROLNOC WAR TOT (©2001 American Med jamanetwork.comy/ on 01/24/2021 After adjusting for age, sex, and education, low, mod- crate, and high levels of physical activity were related to lower risks for CIND compared with no physical acti lty (Table 2). Likewise, moderate and high levels of physical activity were associated with significantly lower risks for Alzheimer disease and for dementia of any type. A similar but nonsignificant eflect was observed with vas- cular dementia, Significant trends for lower risk with « higher level of physical activity were observed in the groups with CIND (P<.001), Alzheimer disease (P=.02), and dementia of any type (P=.04), ‘Associations between physical activity and risk of IND and dementia were examined separately for men and women (Fable 3). Among women, after adjusting, forage and education, regular exercise was associated with significantly lower risks of CIND, Alzheimer disease, and dementia. The ORs were lowest for the highest level of physical activity, showing approximately 50% redue- Association, All rights reserved.sscessed with an independent sample of 738 elderly indi idhals, to whom the risk factor questionnaire was admin fstered by an interviewer. Construct validity was assessed by comparing the combined score with other reported. markers of health hypothesized to be related to exercise and self-rated health. The average intraclass coelicent for the combined score was 0.76 (05% confidence interval [ci], 0.72-0.79; P=002), while the combined score dem- onstrated satisfactory construct validity, and seemed to be well associated with mortality over 5 years.” Ethical approval for the study was obtained from eth- {es review boards in all participating centers. Subjects liv fngin the province of Newfoundland had to be excluded fom, (CSHA-2 final analyses, because of recent provincial legisla- ton restricting the possibility of obtaining consent from prox tes for partiipation of mentally incompetent subjects, DESIGN The effec of physical activity on cognive impairment and dementia was analyzed using case control approach within the CSHATT cohort, with incident cases and contol se lected atthe end of CSHA-2 Tobe inched inthe analy sis sect nally had to be screened negative or with out dementia or CIND according tothe links evaluation, ‘he fellowing 4 outcomes were examined according to CCSHA-2 final dagnose:CIND, Alzheimer disease, vase lar dementia, and any typeof dementia The diagnosis of dementia for these analyses was based on the Diagnostic tnd Slaistial Mana of Blental Disorders, Fourth Editon criteria.” Subjects who remained without cogaitve im- parent or dementia in CSHA-2, cording tothe sreen- Ing test and/or the clinical evaluation, served as controle 2h end point was examined among controle only and Consisted of whether they experienced a reduction of 5 poinisormorecon the 3Ms Exanination score from CSHA-1 (oCSHA2 STUDY POPULATION (Of the 9008 subjects in the original sample at CSHA-1, 4442 subjects from Newfoundland were exeluded from the analyses as were 829 subjects diagnosed as having CIND for dementia in CSHA-1, Of the remaining 7740 eligible subjects, 434 (83.1%) subjects had a risk factor ques- Uonnaire available. Subjects who died during the follow-up period (1=1172), who relused to participate in CSHA-2 (n=374), or who were lost to follow-up (1=273) also were excluded, leaving 4015 subjects. Of these, 3894 were still not cognitively impaired in CSHA-2 (controls) find 436 were disgnored as having CIND, 194 Alzheimer disease, 61 vascular dementia, and 30 other specific oF ‘unclassifiable dementi, STATISTICAL ANALYSIS Five separate analyses were performed to assess the aso- clations between exercise and Incident cognitive lose, CIND. Alzheimer disease, vascular dementia, and any type of dementia, Univariate and multivariate logistic regression models were used to analyze the crude and Adjusted ods ratios (ORs) forthe 5 end points, Age, tex, and education were included in-all multivariate tmodele as potential confounders; age and education twere entered as continuous variables, Other variables Ceamined ss potential confounders included the follow- ing family history of dementia, regular smoking: regular aeohol consumption; use of nonsteroldl anteinfam matory drugs; summation score forthe 7 ems ofa ‘ies of dally Ge, eating transferring [le the capacity to getin and out of bed} toileting, grooming, dressing, talking. and bathing); a summation score for the 7 items of instrumental activites of daly living (le, sll meeting tens hing ney, mel re fated health; and number of reported chronte diseases from alist of 10 condiions (Je, heat disease, hyperten- son, cancer, stroke and other neurologic disease, thr, ules, diabetes mel, thyroid disease, kidney disease" and depression). Modification of rk by age sex, education, and family history of dementia was investigated using iteration terme. x? Tests for linear trend were performed using the level physical activity ‘atlable san ordinal variable in adjusted models tions in risk of CIND and dementia, and a 60% redue- tion for Alzheimer disease, as compared with no physi- cal activity. Trends in decreasing risk with increasing levels, of activity were significant for CIND (P<.001), Alzhel- mer disease (P=.03), and dementia (P= 02). Among men, associations between levels of physical activity and de- ‘ereased risk of CIND and dementia were observed, but none were of statistical significance. No interaction was found between regular physical activity and age, educa- story of dementia (data not shown). The association between physical activity and tisk of CIND, cimer disease, and dementia, according to sex and adjusted for several potential confounders, is given in Table 4. Estimates of ORs for men and women were sim lar to those reported earlier, but some lost statistical sig- nificance. Among women, tests for trend remained sig- nificant for CIND (P<.003) and Alzheimer disease (P=.05), but did not reach statistical significance for de- mentia of any type (P=.18), (aepnostep) ARCH NETROLNOC WAR TOT (©2001 American Med jamanetwork.comy/ on 01/24/2021 Table 8 gives the association between physical ac- Livity and risk of a 5-point loss on the 3MS Examina- tion, according to sex among controls only. After adjust- ing for age and education, no association was found for men, whereas a significant protective effect was ob- served for the highest level of physical activity among, women (OR, 0.58; 95% Cl, 0.40-0.82). A significant trend, foran increased protective elect with higher level of physi- calactivity was noted in women (P<.01), but not in men. a This large-scale, prospective cohort study showed a sig- nificant protective effect of regular physical activity on the risk of cognitive impairment and dementia, particu- larly of the Alzheimer type, in a representative sample of the Canadian elderly population, These associations were observed mainly in women and revealed a signili- cant dose-response relationship showing decreasing risk. Association, All rights reserved.‘Table 1. Characteristics at Baseline of Study Population, Decedents, and Nonrespondents* one ecoae Nonresponcente arabe (o= 3009 (2280) (watt) (a=007) ony cere 217 (505) 138,817) 53186) 346 204) 238445) 1025 (358) 210,482) 159,637) 510 (468) 22 (488) 152(89) 38202) 7927) 278 (237) THD) sm Ne 1543 (308) sro (ait) 100 282) 585 (482) 221 381) Female 2351 (604) 257 (689) 176 61.3) 607 618) 220,649) Eduetiona ley oe 980 252) 201 (462) 8 (249) 392 (335) 213(380) 2 1750 453), 183,375) sn7 (418) 523 (447) 215(«238) 1147 (205) 71063) 65235) 255218) 156 (242) Regular physica activi None 1103 (300), 160 (442) 110 (444) £85 (610) 219(371) Low 485132) 44018) 24013) 138127) eat) Moderate 1360 (37) 122,319) 79(319) 287/063) 211 (353) High 71 (109) 471123) 31128) 109 (102) 91154) “Al lus ar expressed as numbers pecetaes).CIND ndeates cote impale no dementa {Physical actly was he compost seoreobtaned by summiog arses fhe fequncy question = mes per week wee) ar ess than wee) nthe nasty question (more vigorous, quilt a ss gorous than ling) 00 he Canaan Sty of Heath and Aging Seo te ‘Sujets and Methods secton for futher explanation ‘Table 2, Relationship Between Physical Activity and Risk of Cognitive Impaitment-No Dementia (CIND) and Dementia ‘Dement eno vascular Type ‘ay Type me. ot cases) ho. of ase) Wo. oases) Ne. of ase) Necotcontes oR (@9% cI)" Wo. of Contols Of (@3% Cl) No. eConkols OR (8% ci) No ef Conois Om (89% ci) yee aeigh None tenia 3.00 avii03 40 ania soo siamo 4.00 Low id85 065 (046-095) 211485 OT(O3B418) 5485 OSL 2014s) 7885 a6 (AT-1.0) Moderate 12/1360 067 (052-087) S21360 OT (0N6-098) 18/1360 070(037-131) Ta/36o 069 (080.095) High 41731 OS8(01-083) 16731 050(028000) ws} CeB(O2r-14s) 30731 068 (040.098) Test for wend Pot = 2 ary = 04 OR dates ods ae; contence tea bata are aust for. tll evel See the “Sublets and Methods" section fr an explanation ofthe phys actu catego. with increasing level of physical activity. We also found dementia and did not include specific measures of phy'i- 4 lower risk of cognitive loss associated with intensive cal exercise. Finally, Broe et al conducted a 3-year fol- regular physical activity among elderly women who re- low-up study of 327 people in Australia and reported no mained cognitively normal during the study period, association between physical exercise (ranging [rom gar- Few other prospective stidies have examined the dening to sports or walking) and risk of dementia or per- association of regulat exercise with the risk ofdementia formance to a series of cognitive tess, in elderly populations. In Japan, Yoshitake al" fol- (Our results are based on a large representative lowed up a cohort of 828 people for 7 years and re- sample, using a rigorous prospective design, avoiding bi- ported a relative risk of 0.20 for Alzheimer disease in __ases related to retrospective assessment of regular exer- physically active compared with nonactive subjects, but _cise and other exposures. In addition, participation rates did not find any association for vascular dementia. These remained high™ throughout all phases of the study" and, analyses were based on small samples of incident cases, subjects were assessed using an extensive standardized and measurement of physical activity was limited to a diagnostic protocol including clinical evaluations by a phy- 4-category question on intensity ofphysical activities from _sician and a neuropsychologist leisure to work. Li et al” completed a 3-year follow-up ‘Our study also has limitations. OF al eligible sub- study of 1090 people in China and found a relative risk jects at baseline for whom a risk factor questionnaire of 8.7 for dementia in subjects limited to indoor activi was available, 1172 (18.2%) died during the 5-year tues, compared with those without such limitations. The follow-up period and were excluded from the analyses. less study, howeve was based on only 13 incident cases of These subjects were, at baseline, generally older, (©2001 American Med Association, All rights reserved.‘Table 3, Relationship Between Physical Actvty and Risk of Cognitive Impairment-No Dementia (C1ND) and Dementia, According to Sex eno Any Type he. of ase) Wo. of cases) No-et contol on (ear ci)" __—nacatCenlele oR (BETH) Na ofContale OR BBY ch), Physi actviyt None ss00 1.00 re) 1.00 ana 1.00 Low jane 088030411) 69 sr (038219) ‘te 88 0.42186), Moderate eas a2 62.138) 17825 68 (038137), 33625 oazio4etai) igh pases 088 0.42111) 1386 067 (020-150) 10886 (045-155) Test for wend Pe 36 Pat Priel activity None tata 100 emo 1.00 aur 1.00 Low 31316 071 (045-100) ‘016 060 031-110) 1826 035 031-097) Moderate sams 0 82,037.074) 825 167 (042-106), 451835 oe 043.005), High juss 083,031.08) 7388 038(0.16091) 125 048 025008) Test for wend Poot Pas pee OR dates oda; contence nea {Data at aque forage and educational vel Sethe “Subets nd Method section fan explanation of the py actly catego. ‘Table 4. Relationship Between Physical Actvty and Risk of Cognitive Impairment-No Dementia (CIND) and Dementia, According to Sex and Adjusted for Several Potential Confounders ‘Dement ID, oF (29% C)* 88, OF (29% Ct ‘Any Typ, OF (9% Regular physica activi None 1.00 1.00 1.00 Low 065 (020-138) 087 (0.26200) 096 0.40231) Moderate oe (058-134) 051 (025-150) 072 038-138) High 068 (030-120) 073,027198) 01 (045-183), Test for wend Pa P=.50 Regular pial acy None 100 100 1.00 Low 060 (041-1.16 070 033.149) 063 032-125), Moderate 05 (036-082) 037 (ost-143) 087 (055-139), High 0 (025-000) 027 (008.090) 055(025-121), Test for wend P=.003 P=5 Paste OR deat oda, contence nea 0d aos ar adjusted fo ape, sx educational eel smotng, alto use of nonsteroidal antintammatry drugs, neta aby in base ang lostumentl atte of daly hg, the pst atin categories. ‘educated, less physically active, and suffered more fre- {quently from chronic diseases than subjects who com- pleted follow-up. Excluding decedents may have pro- duced distortions in the results, if they were both less physically active at baseline and at high risk of develop- ing cognitive impairment or dementia. In a recent arlicle by CSHA investigators presenting ineidence fig- ures for dementia in Canada," an effort was made to estimate the probability of dementia for subjects who died during follow-up, Irom the following 3 sources: (Q) the mention of dementia on death certificates; (2) information from proxies about a diagnosis of memory aed heath, andi number of cron heath condos. Se ite "Subjcsand Methods set fan expaton of problem, Alzheimer disease, or senile dementia prior to death; and (3) a logistic regression model estimating the probability that the deceased person was demented prior to death, based on an analysis of 71 people who died within 2 to 5 months of undergoing a complete diagnostic evaluation, These estimates could be obtained for most decedents, but were unavailable for nonrespondents. Using one or more of these criteria, 21.2% of decedents could he classified as having devel oped dementia during follow-up. When analyses were redone including 249 decedents as demented cases and 773s nondemented controls, the observed associations lation, All rights reserved.‘Table 5, Relationship Between Physical Actvty and Risk of Cognitive Loss, According to Sex, Among Cognitvely Normal Subjects cogarive Loss Mo, otasespo. of Conrls om (9% cy" fo. otcasespo. of Conrols (08 (9%) igs aeiph None 113280 1.00 170853 1.00 Low asa 095 053-14) tas? 1.06 0.78-1.45) Moderate 124301 35 (052-115), 18253 asz(ore17) igh 111283 98,0.7-135) 407206, 038 04008) Test for wend post OR nates odds ate; Cl, contence tea $Date aguste forage and educatonal level Se the “Subjects and Metods section for an explanation of hepsi acy catego. between physical activity and risk of dementia persisted and were even more statistically significant. This sug- ‘gests that exclusion of deceased subjects from our study had litle effect on our results, if anything making esti rates somewhat conservative Ic might be argued that engaging in regular physi- cal activity does not perse play a protective role on cog- nition and cognitive disorders, as suggested by our study but rather can he viewed merely as a marker of good health, being itself related to lower risk of cognitive im- pairment and dementia, We tried to examine this hy- pothesis by adding in our logistic models variables re- lated to health status, and observed that risk estimates remained very similar to those reported for men and women when controlling for age and education only. Despite the prospective nature of the study, our te sults might possibly be explained by some preclinical cog- nitive decline (not yet detectable by screening and clinical ‘evaluations at CSHA-1) among subjects who later devel- ‘oped CIND or dementia by CSHA-2. Ifso, lower physical activity could then be a consequence of CIND or demen- tis at is preclinical sate rather than a risk factor. In this ‘context, we reanalyzed our data excluding subjects who reported early cognitive symptoms in the first 2 years of follow-up and obtained practically unchanged results. More- ‘over, the fact that the protective ellect of exercise on cog- nitive loss persisted among subjects who remained with- ‘out CIND or dementia during the whole 5-year follow-up period does not favor this hypothests of « preclinical state forexplaining our results, although it cannot be ruled out Several mechanisms may underlie the potentially pro- Lective ellects of physical activity on cognitive function. I has been shown that physical activity sustains cerebral blood ow” by decreasing blood pressure, lowering lipid levels, inhibiting platelet aggregabilty, or enhancingcerebral meta- bolic demands. There is also evidence that exercise may improve aerobic capacity and cerebral nutrient sup- ply." More recently, experimental studies in rodents in- dicated that growth factors could be involved.” To our knowledge, our results suggest, for the first time, that ex- tercise may be protective especially for women. Apparent lack of association between exercise and CIND and de- mentia in men could be attributed to insufficient mum bers of cases. Stronger associations found in women could also be related to some interaction between exercise and, hormone metabolism, Endurance exercise training has been (©2001 American Med jamanetwork.comy/ on 01/24/2021 shown to have an independent but complementary el to hormone replacement therapy on serum lipid profiles in healthy postmenopausal women. ‘Our study suggests that engaging in regular physical activity, among other health benefits, may delay or prevent the onset of cognitive impairment and dementia in the el- derly, especially in women. Although these findings will eed confirmation in further epidemiological and intervention studies, this study suggests that regular practice of phy’ sal activity could represent an important and potent pro- ‘clive factor for cognitive impairment, Alzheimer disease, and other dementia in the elderly population. Accepted for publication November 29, 2000. Data reported in this article were collected as part of the CSHA. The core study was funded by the Seniors’ Inde- pendence Research Program, through the National Health Re- search and Development Program (NHRDP) of Heath Canada (Project No, 6606-3954-MC [S]). Additional funding was pro- vided by Pfizer Canada Inc through the Medical Research Council/Pharmaceutical Manufacturers Association of Cama Health Activity Program, NHRDP (Project No. 6603-1417- 302 [R)), Bayer Inc, and the British Columbia Health Re- search Foundation (Project Nos. 38 [93-2] and 34 [96-1)) Ms Laurin was supported in part by a National Health PhD Fellowship provided by the NHRDP (Project No. 6605-5228. 47) and by the Laval University Chair for Geriatric Re- search. Dr Verrealt is supported bythe Laval University Chair {Jor Geriatric Research This study was coordinated through the University of Ottawa and the Division of Aging and Seniors, Health Canada. We are grateful to Susan Kirkland, PhD, for her com- iments on an earlier draft of the manuscript. Corresponding author and reprints: René Verreaull, MD, PhD, Laval University Geriatric Research Unit, Cen- tre dhebergement St-Augustin du Centre hospitalier afiie universitaire de Quebec, 2135 Terrasse Cadieux, Beau- port, Quebec, Canada GC 122 (e-mail: Rene.Verreault @msp.ulaval-ea), EES] 1. Cabs EL Ral Heath of ler women. Med Nar Am 109882 artes 2 Muara Cotman GW, Kavas Ct al othe lie’ Disease Cope Association, All rights reserved.Bn 18 6 ” ® 0 2 a 2 a en 28 a. Ey Ey on n 2 a Downloaded From:: ‘ine Su. Eogen pact hay far anmar of milo odeate AE hina sexe a andonze onpolea Wa JU 200023 007-105, drson VW Page Miler, ea Exon for Ashamed ‘zen waren: ndomied, double ln plrsh-onvoea via Merlo Svs 308 Forte. Seu iL Steen Ao Preto of emartiinranoiend ‘oul bing parake courted Syke yperensienin ups (9st eat oes sara Gio Frail L nu Fastom J, Wtad 3, VanenM. Occurence and Pofeson of dara ia communi popdaton age 75 Jer ard ol: Felatonsip of anthyparansive medeaon use. Ach Newel 100056901 os Sars, Mander A. Ugo jd, Christoph. A oul ind, labo ‘aneledio eteralnsopesialin Achrnersese, eaaly 195 srr Fragen LEpfenisogy of Achinas disease and cure posses fr pevenion et New Seand Sop 1008165300 ‘Du Cl Eider ote dren: rec delopmets anne ap preaches. J Neuro Aeurasurg Pychay. 1966047888 Eo PB Shu of ek tr for denen sane wih sla, Stoke, arabs. ry He Extn SU. ue aang Nor Am 00478367.76 GPS Stamper Clit, tal Pysalactty and shot sels nwa daa 02820612067 Patenuger RSJ, Hye ST Wng AL Le Jung Kaper. The ase ‘Sor ofchangesa yal arb andar wh totality among mh. HE! / Med. 1093:28 5585, ‘ope Par Gertie aie JANA 1007-27-1863186, Elon. Gait eine. Ie 1899 SE. Ferns L.tmian, Level Sel Smoking, psa, nd ave Me oxpectaney AJ pe 190 406 88, Nar Jaze Bare adh pshlogial sao stueand ty {ews Prep lr She 1004791107 1118. Cet. ZatoW. Pry as, ogni ptmane an apo, Med Se Spo Ber 191 288-72 Okuma, Masubayes K Wal, iru , Dl, Cru TEs fx ‘looser uton commun dling ce peopl tan years of ape. Ae Ger Sae 00544260572 ogee Maer Monel Ar echngretemen pyc tty Sts crralartsin ard comion Am Gea So 19038123128. Wellrdo ME Sune Randomised ara wralt xcs the ty Goran 1008 200-208 Ener GF Ga Mt Psjealogeal and cognv ects of an exeise progam {or aman-esing oder ius. Georg. 1080307180188 Wits Lad eal grou exsteseon cope ncn ard mood Inoler omen Aus 2 Pabe aah 0872045 52 ‘se ial AL Yoga ict ast ew phil nes eae andar an nee progr Jaana 80 ‘Bande Distan Rung RO, ssl Meta acc owdneuropsytclogial uncon of erin Son ort prctone. Masa rcs wating adi ewabel gy. 06 HID, Sorat, Maley M. Thc ng arm exec tng ony ‘holga! nctonn ln acu J Geant T0058 P12 Pr CaaS Hare Ad. Rlcstps etwse yc neti ardcog nie bis in ads, Payot Aging 1084 18-18. Suey Karma & Sons I. Srp copie até bahaoural changes re =uling am proved pyses ines mpeteans ove 80 yeas pe. 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