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      Aspirin, NSAIDs, Risk of Dementia, and Influence of the Apolipoprotein E Epsilon 4 Allele in an Elderly Population

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          In a cohort study, 1,301 subjects free of dementia at baseline in the Kungsholmen Project were followed up to 6 years. We studied the association between use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), incidence of Alzheimer’s disease (AD) and overall dementia, and the influence of the apolipoprotein E Ε4 allele. In stratified analyses, a relative risk (RR) of 1.80 (95% CI 1.14–2.83) for AD was seen, in the apoE Ε4-negative group using aspirin. This implicates a possible different mechanism of developing AD in this group. We also found a possible protective effect of NSAIDs against AD, since no one who used NSAIDs for around 3 years had developed AD 3 years later. One user developed vascular dementia, and a low point value of risk was seen, however, not significant (RR 0.23; 95% CI 0.03–1.68). This could be due to the small samples in our study, or to comorbidity contributing to the development of dementia in this elderly population.

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          Most cited references 13

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          Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging.

           J. Lindsay (2002)
          A prospective analysis of risk factors for Alzheimer's disease was a major objective of the Canadian Study of Health and Aging, a nationwide, population-based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615 were alive in 1996 and participated in the follow-up study. All participants were cognitively normal in 1991 when they completed a risk factor questionnaire. Their cognitive status was reassessed 5 years later by using a similar two-phase procedure, including a screening interview, followed by a clinical examination when indicated. The analysis included 194 Alzheimer's disease cases and 3,894 cognitively normal controls. Increasing age, fewer years of education, and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine consumption, coffee consumption, and regular physical activity were associated with a reduced risk of Alzheimer's disease. No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, smoking, high blood pressure, heart disease, or stroke. The protective associations warrant further study. In particular, regular physical activity could be an important component of a preventive strategy against Alzheimer's disease and many other conditions.
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            Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.

            Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.
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              Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study.

              To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years. General population in Rotterdam, the Netherlands. A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline. Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia. The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia.

                Author and article information

                S. Karger AG
                June 2004
                16 April 2004
                : 23
                : 3
                : 135-143
                Aging Research Centre, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Stockholm Gerontology Research Centre, and Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden
                75957 Neuroepidemiology 2004;23:135–143
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 4, References: 61, Pages: 9
                Original Paper


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