Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Exposure to polychlorinated biphenyls and organochlorine pesticides and risk of dementia, Alzheimer's disease and cognitive decline in an older population: a prospective analysis from the Canadian Study of Health and Aging.

BACKGROUND: Little attention has been paid to neurotoxicants on the risk of dementia. Exposure to known neurotoxicants such as polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is suspected to have adverse cognitive effects in older populations. OBJECTIVE: To assess whether plasma concentrations of PCBs and OC pesticides are associated with the risk of cognitive decline, Alzheimer's disease (AD) and of all-cause dementia in the Canadian older population. METHODS: Analyses were based on data from the Canadian Study of Health and Aging, a 3-phase, 10-year population-based study of individuals aged 65+ years. Analyses included 669 clinically assessed subjects, of which 156 developed dementia including 108 incident cases of AD. Subjects were screened at each phase with the 100-point Modified Mini-Mental State Examination (3MS), a measurement of global cognitive function. Statistical analyses included Cox proportional hazards model when the outcome was dementia or AD, and a repeated-measure mixed model when the outcome was the 3MS score. RESULTS: No association of PCB and OC pesticides with the risk of dementia and AD was observed. Elevated concentrations of PCB congeners nos 118, 153, 156, 163, and OC pesticides 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) were significantly associated with cognitive decline as assessed with the 3MS. A posteriori analyses suggested that only p,p'-DDE was significantly related to a higher cognitive decline in time based on the 3MS among incident cases of dementia compared to subjects remaining nondemented. CONCLUSION: PCB and OC pesticide plasma concentrations were not related to the incident diagnosis of neither dementia, nor AD. Using the 3MS scores as the outcome, higher concentrations of four PCB congeners and two OC pesticides were associated with lower cognitive performances in subjects. The association of p,p'-DDE with cognitive decline in time in incident cases of dementia merits further investigation.

Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer's disease.

BACKGROUND: Some observational studies have established an association between exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and a decreased risk of subsequently developing Alzheimer's disease (AD). Mild cognitive impairment or cognitive impairment, not dementia (CIND) is more likely to convert to AD, and no specific preventive method is currently available. The objective of this study was to determine the association of NSAID use in 5276 cognitively normal subjects of the Canadian Study of Health and Aging, a 10-year population-based cohort study, with the incidence of CIND, AD, and all-cause dementia. METHODS: Hazard ratios were calculated from Cox proportional hazards models with age as the time scale according to three study samples including 824 cases of dementia (563 cases of AD), 630 cases of dementia (435 cases of AD), and 883 cases of CIND, respectively. Adjustments were made for gender, education, lifestyle factors, comorbid diseases, and vascular risk factors. RESULTS: Lower risks for AD and all-cause dementia were significantly associated with the use of any NSAIDs and the salicylates without barbiturates subgroup in the study sample including subjects with CIND at baseline. There was a weak association between any NSAIDs and the risk of CIND (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00). CONCLUSION: These results suggest that there is an association between NSAID use and a lower incidence of AD and, to a lesser extent, of CIND.

Polychlorinated biphenyls and organochlorine pesticides in plasma of older Canadians.

No nationwide study has ever measured polychlorinated biphenyl (PCB) and organochlorine pesticide (OCP) body burden in Canadians aged 65 years and over. The objective of this study was to determine plasma concentrations of PCB congeners and OCPs in participants from a sub-cohort of the Canadian Study of Health and Aging and to examine the effects of socio-demographic, anthropometric and lifestyle characteristics on selected organochlorine concentrations. Archived plasma samples collected from 2023 subjects were analyzed by gas chromatography-mass spectrometry using negative chemical ionization for 15 PCB congeners and 11 OCPs. Descriptive statistics were used to report PCB congeners and OCP plasma concentrations. Multivariate models were used to study whether age at blood collection, sex, education, body mass index, rural residence, geographic region, smoking status and alcohol intake influences PCB 153, the most abundant congener, and the major OCP (beta-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor, p,p'-DDE) plasma concentrations. Statistical analyses were restricted to 1979 subjects and 17 organochlorine compounds for which at least 50% of the samples had concentrations above the limit of detection. Of these, 775 were men (mean age: 82.2 years) and 1204 were women (mean age: 84.6 years). The median concentrations (ng/g lipid) of PCB 153 in the plasma of men and women were 70.9 and 75.4, respectively. The levels of the sum of PCBs and the sum of dioxin-like PCBs were 276 and 31.3 for men, and 300 and 45.5 for women, respectively. The median concentrations (ng/g lipid) of p,p'-DDE, the most abundant OCP, were 565 for men and 828 for women. All compounds were positively and significantly intercorrelated (rs=0.39-0.99; p<0.001). Except for trans-nonachlor, the multivariate models revealed that age and male sex were the determining characteristics that showed, respectively, strongly positive and negative associations with selected organochlorine concentrations. These plasma concentrations from a large population based study can be considered as baseline data for body burdens of older Canadians.

Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 µg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Vascular risk factors and cognitive functions in nondemented elderly individuals.

BACKGROUND: The brain-at-risk stage is the earliest phase of the vascular cognitive impairment continuum and includes individuals with vascular risk factors (VRF). However, there is still no clear definition of this concept. The aim of the study is to characterize the neuropsychological profile of elderly individuals by 3 levels of VRF. METHODS: This is a cross-sectional analysis of the Canadian Study of Health and Aging baseline data; 577 nondemented elderly individuals > or =65 years old were divided into 3 groups: reference group (0 VRF; n = 82); intermediate brain-at-risk group (1-2 VRF; n = 360); high brain-at-risk group (> or =3 VRF; n = 135). A principal component analysis (PCA) and univariate/multivariate analyses of variance were performed to examine the relationships between the groups and various cognitive measures. MAIN FINDINGS: The PCA produced a 2-component solution (1) executive/psychomotor functions including measures of abstraction and (2) verbal memory. The high brain-at-risk group performed significantly worse than the reference group on the first component. CONCLUSIONS: Elderly individuals presenting with > or =3 VRF are more impaired on measures of executive functions/ processing speed than participants without any VRF.

Is complexity of work associated with risk of dementia? The Canadian Study of Health And Aging.

The authors evaluated the association of complexity of work with data, people, and things with the incidence of dementia, Alzheimer's disease, and vascular dementia in the Canadian Study of Health and Aging, while adjusting for work-related physical activity. The Canadian Study of Health and Aging is a 10-year population study, from 1991 to 2001, of a representative sample of persons aged 65 years or older. Lifetime job history allowed application of complexity scores and classification of work-related physical activity. Analyses included 3,557 subjects, of whom 400 were incident dementia cases, including 299 with Alzheimer's disease and 93 with vascular dementia. In fully adjusted Cox regression models, high complexity of work with people or things reduced risk of dementia (hazard ratios were 0.66 (95% confidence interval: 0.44, 0.98) and 0.72 (95% confidence interval: 0.52, 0.99), respectively) but not Alzheimer's disease. For vascular dementia, hazard ratios were 0.36 (95% confidence interval: 0.15, 0.90) for high complexity of work with people and 0.50 (95% confidence interval: 0.25, 1.00) for high complexity of work with things. Subgroup analyses according to median duration (23 years) of principal occupation showed that associations with complexity varied according to duration of employment. High complexity of work appears to be associated with risk of dementia, but effects may vary according to subtype.

Omega-3 fatty acids and risk of cognitive impairment and dementia.

It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline. This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia. Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves (1991-1992 and 1996-1997) of the Canadian Study of Health and Aging. Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline. Results were adjusted for age, sex, education, smoking, alcohol intake, body mass index, history of cardiovascular disease, and apolipoprotein E e4 genotype. In the cross-sectional analysis, no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia. In the prospective analysis, a higher eicosapentaenoic acid (p < 0.01) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid (p < 0.07), omega-3 (p < 0.04) and total polyunsaturated fatty acid (p < 0.03) concentrations were found in dementia cases. These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia.

Neyman's bias re-visited.

In case-control studies using prevalent cases, an apparent association may be spurious if the risk factor affects survival. In his description of this potential bias, Neyman disregarded competing risks. We use a compartment model to illustrate Neyman's bias and show that it can explain the apparent association only if the risk factor influences mortality from the disease being studied. Any effect of the risk factor on mortality from other causes is not relevant. The apparent protective effect of smoking in relation to Alzheimer disease is used as an example, but the result holds for any irreversible noncommunicable disease and for any dichotomous risk factor.

Prevalence and correlates of overweight and obesity among older adults: findings from the Canadian National Population Health Survey.

BACKGROUND: The prevalence of obesity among elderly persons in industrialized countries ranges from 15% to 20%. Little is known about variations of overweight within subgroups of the elderly population. This study examined the factors associated with overweight and obesity among older men and women. METHODS: Data for 12,823 community-dwelling persons aged 65 and older from the 1996-1997 Canadian National Population Health Survey were examined. Predictors of overweight (body mass index [BMI] = 25.0-29.9 kg/m2) and obesity (BMI = >30 kg/m2) relative to normal weight (BMI = 20.0-24.9 kg/m2) were examined using logistic regression analyses. Analyses were stratified by gender. The predictor variables included age, education, marital status, place of birth, region, smoking status, alcohol use, chronic conditions, physical activity, functional limitations, self-rated health, social support, and psychological distress. RESULTS: Overall, 39% and 13% of Canadian older adults were classified as overweight and obese, respectively. Some of the risk factors for overweight were male gender, low education, being married, Canadian born, residence in the Atlantic provinces, no use of alcohol, comorbidity, physical inactivity, and limited functional status. Risk factors for obesity were similar to those for overweight except for being unmarried; American, European, and Australian born; lower and higher levels of alcohol use; poor self-rated health; and psychological distress. CONCLUSIONS: The results could lead to more effective weight-control interventions that are designed to promote increased physical activity and healthy eating habits among obese older individuals.

Dementia / Alzheimer's Disease.

HEALTH ISSUES: Dementia, including Alzheimer's disease (AD) increases exponentially with age from the age of 65. The number of people with dementia will increase significantly over the next three decades as the population ages. While prevalence and incidence rates do not differ markedly in women, compared to men, women live longer on average, so the number of women with dementia is greater than for men. Also, women are more frequently caregivers for people with dementia. Thus, dementia is an important health problem for women. KEY FINDINGS: The Canadian Study of Health and Aging showed an increase in prevalence of dementia with age for both sexes, approximately doubling every five years of age. Rates of AD were higher in women whereas rates of vascular dementia were higher in men. The risk of AD increased with increasing age, lower education, and apolipoprotein E epsilon4. Regular physical activity was clearly protective in women; this was less clear for men. Use of non-steroidal anti-inflammatory drugs, wine consumption, and past exposure to vaccines decreased the risk of AD. Estrogen replacement therapy did not reduce the risk of AD. About three quarters of caregivers for dementia patients were women. DATA GAPS AND RECOMMENDATIONS: The protective effect of regular physical activity for AD provides an additional reason to promote regular physical activity at all ages. Ongoing surveillance of the incidence, prevalence and risks for dementia is needed to monitor the impact of treatments as well as the aging of the population on the burden of dementia.

Plasma polychlorinated biphenyl and organochlorine pesticide concentrations in dementia: the Canadian Study of Health and Aging.

BACKGROUND: Even though polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides are recognized as neurotoxicants, few studies have investigated their associations with dementia. Here, we assess associations of plasma PCB and OC pesticide concentrations with all-cause dementia and Alzheimer's disease (AD). METHODS: Analyses are based on data from the Canadian Study of Health and Aging, a population-based study of men and women aged 65+ years at baseline. PCB and OC pesticide concentrations were measured in 2023 participants who had complete clinical evaluations and blood samples; 574 had dementia, including 399 cases of AD. Concentrations were log-transformed and used as continuous variables in logistic regression models to assess their individual associations with dementia and AD. RESULTS: After adjustment for blood collection period, total plasma lipids, age, sex, education, apolipoprotein E e4 allele (ApoE4), tobacco and alcohol use, rural/urban residence, and comorbidities, elevated plasma PCB concentrations were not associated with increased prevalence of dementia and AD. Elevated concentrations of some OC pesticides and metabolites such as hexachlorobenzene, cis-nonachlor and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane were significantly associated with a reduced prevalence of dementia. A significant reduced prevalence of AD was also observed with elevated hexachlorobenzene concentrations. Other OC pesticides and metabolites were not associated with the prevalence of dementia or AD. No effect modification by sex and ApoE4 was observed for either dementia or AD. CONCLUSIONS: Elevated plasma PCB and OC pesticide concentrations were not associated with higher prevalence of all-cause dementia and AD. The possibility of modest reductions in prevalence with specific OC pesticides remains to be further investigated given the cross-sectional design of this study.

Genetic determinants of "cognitive impairment, no dementia".

Dementia is a heritable condition with devastating effects on both patients and their caregivers. Studies have identified genetic variants associated with increased susceptibility to late-onset Alzheimer disease (AD)-related dementia; however, no studies have assessed whether genetic variation is associated with the early stages of cognitive decline. Given that cerebrovascular disease is an established mechanism in which chronic ischemia increases susceptibility to dementia, we assessed whether genetic variation associated with either cardio-metabolic or AD-related traits is associated with an early stage of cognitive decline called "cognitive impairment, no dementia" (CIND). We studied 484 CIND patients and 459 cognitively healthy controls selected from the Canadian Study of Health and Aging. We tested for association between ~200,000 genetic variants selected from genes associated with cardio-metabolic traits and CIND status using the Cardio-MetaboChip. We also assessed whether AD-related variants and APOE alleles were associated with CIND status, either individually or as part of a composite genetic risk score. We identified a potential association between the ZNF608/GRAMD3 locus, specifically the rs1439568 polymorphism and CIND status (major allele odds ratio [OR] = 1.51; p = 8.4 × 10(-6)). AD-related variants were not associated with CIND status, however APOE E4 allele frequency was significantly higher in CIND patients versus healthy controls (OR = 1.35; p = 0.044). We identified a potential association between the ZNF608/GRAMD3 locus and CIND status, although AD-related variants were not associated with CIND. Additional replication of this association signal is invited.

Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against dementia, although epidemiologic studies have yielded inconclusive results. Fish is the main dietary source of n-3 PUFAs and is sometimes contaminated with mercury. This neurotoxicant may modify the association with dementia. OBJECTIVE: We evaluated the association of erythrocyte membrane total n-3 PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and blood mercury with the incidence of dementia and Alzheimer disease (AD) in the Canadian Study of Health and Aging (CSHA) with adjustment for confounders including apolipoprotein E epsilon4 (APOE epsilon4) status. DESIGN: The CSHA is a cohort study of a representative sample of persons aged > or =65 y, conducted from 1991 to 2002. A subsample of 663 nondemented CSHA subjects with a complete clinical examination, blood samples, and follow-up information was eligible for prospective analyses on laboratory measurements. Of these, 149 were incident cases of dementia, including 105 with AD. RESULTS: In adjusted Cox regression models with age as the time scale, there were no associations between total n-3 PUFAs, DHA, or EPA and dementia or AD. In contrast, a mercury concentration in the highest quartile was associated with a reduced risk of dementia (hazard ratio: 0.53; 95% CI: 0.33, 0.88). However, significant risk reductions were limited to subjects with concentrations of both n-3 PUFAs and mercury that were above the median. There was no modification of risk by APOE epsilon4 status. CONCLUSIONS: No associations between n-3 PUFAs and dementia or AD were found. The results regarding mercury may indicate a spurious association.

Planning for end-of-life care: findings from the Canadian Study of Health and Aging.

Steps involved in formalizing end-of-life care preferences and factors related to these steps are unclear in the literature. Using data from the third wave of the Canadian Study of Health and Aging (CSHA-3), we examined the relations between demographic and health predictors, on the one hand, and three outcomes, on the other (whether participants had thought about, discussed , or formalized their end-of-life preferences), and considered, as well, whether relations existed among the three outcomes. Canadian region of residence, female gender, and more years of education predicted having thought about preferences; region of residence, female gender, and lack of cognitive impairment predicted discussion of preferences; and region of residence and not being married predicted whether formal documents were in place. Ontario residents were most likely to have thought about, discussed, and formalized their preferences, whereas Atlantic residents were least likely to. Finally, having thought about preferences was associated with discussion, and having thought about and having discussed preferences were each associated with formalization of preferences. These findings are in keeping with the position that Advance Directives (AD) execution is a multi-stage process. A better understanding of this process may prove useful for the development of interventions to promote planning for end-of-life care.

Mapping the connections between education and dementia.

Explanations for the association between educational attainment and the risk of dementia fall into three main categories. It may arise as an artefact of study methods; education may predict broader socioeconomic circumstances and exposures, or education may reflect brain reserve or cognitive capacity that protect against dementia. Data from the Canadian Study of Health and Aging (N=6646, giving 44,676 person-years of follow-up) are analyzed to test a series of hypotheses reflecting these explanations. Years of education showed a strong association with the risk of dementia (relative risk [RR] 2.1 for those with less than 6 years of education compared to those with 13 or more years; RR=2.9 among survivors). Possible artefactual factors were detected, but were insufficient to invalidate the association. Adjustments for a range of other socioeconomic indicators, health problems and lifestyle factors reduced, but did not remove, the association. Adjustments for intelligence and for an indicator of lifetime mental activity also appeared to account for some but not all of the association. The conclusion is that there appears to be a real association between educational attainment and the risk of dementia 50 to 60 years later; this influence appears to run through a number of different, and sometimes complementary, pathways.

Does cognitive status modify the relationship between education and mortality? Evidence from the Canadian Study of Health and Aging.

BACKGROUND: There is compelling evidence of an inverse relationship between level of education and increased mortality. In contrast to this, one study showed that among subjects with Alzheimer's Disease, those with high education are more than twice as likely to die earlier; however, this result has proven difficult to replicate. We examine the relationship between education and mortality by cognitive status, using a large, nationally representative sample of elderly people. PATIENTS: A representative sample of 10,263 people, aged 65 or over, from the 10 Canadian provinces, participated in the Canadian Study of Health and Aging in 1991. METHODS: Information about age, gender, education, and an initial screening for cognitive impairment were collected; those who screened positive for cognitive impairment were referred for a complete clinical and neuropsychological examination, from which cognitive status and clinical severity of dementia were assessed. Vital status and date of death were collected at follow-up in 1996. The analysis was conducted using survival analysis. RESULTS: Cognitive status modifies the relationship between education and mortality. For those with no cognitive impairment, an inverse relationship between education and mortality exists. Elderly people with cognitive impairment but no dementia, or those with dementia, are more likely to die early than the cognitively normal at baseline, but no relationship exists between education and mortality. INTERPRETATION: These findings do not support previous work that showed a higher risk of mortality among highly educated dementia subjects.

More than the epidemiology of Alzheimer's disease: contributions of the Canadian Study of Health and Aging.

OBJECTIVE: To highlight contributions to knowledge made by the Canadian Study of Health and Aging (CSHA). METHOD: The CSHA began in 1991, with follow-ups in 1996 and 2001. It was national in scope, with 18 study centres and a coordinating centre. It included 10 263 participants; of these, 9008 were in the community, and 1255 were in institutions. In each phase, community participants were screened for cognitive impairment, and where appropriate, cognitive status was determined by a detailed clinical examination. Data on possible risk factors for dementia were collected at baseline. Data on caring for people with dementia were collected in each phase. RESULTS: The prevalence of dementia was established at 8% of those aged 65 years and over; incidence (new cases each year) was about 2%. Cognitive impairment not dementia (CIND) was more than twice as common as dementia. Factors affecting the risk of institutionalization, mortality, and the health of caregivers were examined. The costs of dementia were conservatively estimated at dollar 3.9 billion in 1991. Risk factors for Alzheimer's disease (AD) and vascular dementia are presented; it is noteworthy that physical activity appeared to protect against all forms of cognitive decline, particularly for women. Clinical contributions include the development of norms for several neuropsychological tests. Other topics include the health of those with CIND, predicting dementia, medication use, frailty and healthy aging, and urinary incontinence. CONCLUSION: The CSHA has contributed substantially to knowledge of the epidemiology of dementia, including AD, and to many other topics relevant to seniors' health.