Joan Lindsay

Vascular Dementia Incidence and Risk Factors in the Canadian Study of Health and Aging

BACKGROUND AND PURPOSE Very few population-based studies have systematically examined incident vascular dementia (VaD). From the Canadian Study of Health and Aging cohort, incidence rates of VaD were determined and risk factors analyzed. METHODS This was a cohort incidence study that followed 8623 subjects presumed to be free of dementia over a 5-year period. The risk factors were examined with a nested prospective case-control study. Exposure was determined by means of a risk factor questionnaire administered to the subject or a proxy at the beginning of the study. RESULTS On the basis of 38 476 person-years at risk, the annual incidence rate was estimated to be 2.52 per thousand undemented Canadians (95% CI 2. 02 to 3.02). Including an estimation of the probability of VaD among the decedents, this figure rose to 3.79. For the risk factors study, 105 incident cases of VaD according to the NINCDS-AIREN criteria were compared with 802 control subjects. Significant risk factors were: age (OR=1.05), residing in a rural area (2.03), living in an institution (2.33), diabetes (2.15), depression (2.41), apolipoprotein E epsilon4 (2.34), hypertension for women (2.05), heart problems for men (2.52), taking aspirin (2.33), and occupational exposure to pesticides or fertilizers (2.05). Protective factors were eating shellfish (0.46) and regular exercise for women (0.46). There was no relation with sex, education, or alcohol. CONCLUSIONS The study confirmed some previously reported risk factors but also suggested new ones. It raised concerns about the prescription of aspirin and perhaps other factors related to rural life.

The Canadian Study of Health and Aging Risk Factors for Vascular Dementia

BACKGROUND AND PURPOSE The Canadian Study of Health and Aging (CSHA) was conducted in communities and institutions in 10 Canadian provinces. One objective of the study was to study risk factors for vascular dementia (VaD). METHODS This was a population-based case-control study. It included 129 patients clinically diagnosed with VaD with duration of symptoms no more than 3 years and 535 control subjects, frequency matched by age group, study center, and residence in community or institution, who were clinically confirmed to be cognitively normal. Odds ratios (ORs) were calculated using unconditional logistic regression for potential risk factors for VaD. RESULTS Risk of VaD was associated with history of arterial hypertension (OR, 2.08; 95% confidence interval, 1.29 to 3.35). Other significantly elevated ORs were seen for history of alcohol abuse (2.45), history of heart condition (1.71), use of aspirin (3.10), and occupational exposure to pesticides and herbicides (2.60), as well as liquid plastic or rubber (2.59). The OR for less than 6 years of education compared with 10 or more years was 4.02. CONCLUSIONS The study confirmed some previously reported risk factors for VaD, such as history of heart disease. Higher levels of education seemed to lower the risk or delay onset of symptoms of VaD. Use of aspirin may be a predictor of survival rather than a risk factor. The occupational associations, particularly with pesticides and fertilizers, need further study.

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.

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.

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.

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, Alzheimers 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 Alzheimers 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 Alzheimers 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.

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

Some observational studies have established an association between exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs) and a decreased risk of subsequently developing Alzheimers 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.

An overview of the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging is a multicenter, population-based cohort study of dementia with a sample of 10,263 participants aged 65 or over. Field work began in 1991, and a follow-up study was undertaken in 1996-97. The present article describes the origins and objectives of the study, provides an overview of its design, organization, and data collection methods, and offers a brief summary of the main results.

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 Neymans 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.

Canadian Study of Health and Aging: Study Description and Patterns of Early Cognitive Decline

The Canadian Study of Health and Aging (CSHA) is a national longitudinal study of the epidemiology of dementia in Canada. The CSHA also described patterns of disability, frailty and healthy aging. The study involved 10,263 people aged 65 or over, sampled representatively from the community and from long-term care institutions, and participants were interviewed and assessed clinically in 1991, 1996 and 2001. Over 200 papers have been published from the study; a brief summary of results is given. The current analyses provide descriptive statistics on patterns and correlates of early cognitive decline in the study cohort. Several salient findings emerged: almost half of this representative sample showed no cognitive decline over a 10-year period. Education showed a strong protective effect against decline, but not after age 80. There was little difference in crude rates of cognitive decline between men and women, but after adjustment for disability and cardiovascular risk factors, men showed a greater risk of decline, up to age 80. Among those who experienced cognitive decline, the extent of decline was predicted mainly by age, rather than by baseline cognitive scores. Among those who developed dementia, baseline tests were better able to predict Alzheimer’s disease than vascular dementia. Further analyses designed to elucidate these complex associations are described.