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To evaluate the association between apolipoprotein E (apo E)ℇ4 and mortality, the population attributable risk for mortality withℇ4, and relative contributions of cardiovascular disease (CVD) and Alzheimer's disease (AD).Population-based cohort study.Community-based.Permanent residents of Cache County, Utah, aged 65 and older as of January 1, 1995.Participants were genotyped at the apo E locus using buccal-swab deoxyribonucleic acid. Cardiovascular health was ascertained using self- or proxy-report interviews at participants' residences. AD was diagnosed according toDiagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, and National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders criteria. Utah Department of Vital Statistics quarterly reports were reviewed to identify participants who died.Crude evaluations showed nonsignificantly greater risk of death forℇ2/2 (hazard ratio (HR)=1.66, 95% confidence interval (CI)=0.92–2.76) andℇ3/4 (HR=1.11, 95% CI=0.97–1.26) genotypes and significantly greater risk forℇ4/4 (HR=1.48, 95% CI=1.09–1.96). After adjustment for age, age2, sex, and education, risks increased to 1.98 (95% CI=1.08–3.35), 1.28 (95% CI=1.12–1.46), and 2.02 (95% CI=1.47–2.71), respectively, compared withℇ3/3 genotypes. Adjustment for presence of any CVD did not change the risk of death forℇ3/4 andℇ4/4. Adjustment for AD reduced the risk of death forℇ3/4 (HR=1.13, 95% CI=0.99–1.30) andℇ4/4 (HR=1.59, 95% CI=1.15–2.14). The population attributable risk of death forℇ3/4 andℇ4/4 genotypes combined is estimated at 9.6%.These findings suggested that theℇ2/2,ℇ3/4, andℇ4/4 genotypes have greater early mortality risks. Further analyses showed that AD partially mediates the association betweenℇ3/4,ℇ4/4, and death. [ABSTRACT FROM AUTHOR]

Epidemiological studies of Alzheimer's disease (AD) provide insights into changing public health trends and their contribution to disease incidence. The current chapter considers how the population-based approach has contributed to our understanding of lifetime exposures that contribute to later disease risk and may act to modify onset of symptoms. We focus on the findings from a recent survey of an exceptionally long-lived population, the Cache County Utah Study of Memory, Health, and Aging. This study is confined to a single geographic population has allowed estimation of the genetic and environmental influences on AD expression across the expected human lifespan of 95+ years. Given the emphasis of this text on the behavioral neurosciences of aging, we highlight within the current chapter the particular contributions of this population-based study to the neuropsychology of aging and AD. We also discuss hypotheses generated from this survey with respect to factors that may either accelerate or delay symptom onset in AD and the conditions that appear to be associated with successful cognitive aging.

Background: The APOE epsilon4 allele is an established risk factor for Alzheimer's disease, but reports of its association with vascular dementia (VaD) have been inconsistent. We examined the relationship between APOE epsilon4 allele and the risk of incident VaD in a large, population-based cohort of elderly adults with up to 10 years of follow-up between 1995 and 2005., Methods: A total of 3,424 elderly men and women free of dementia were genotyped at the baseline assessment. Incident VaD was identified through standardized procedures administered at 3 follow-up assessments. Cox proportional hazards models were used to evaluate the risk of VaD associated with APOE epsilon4., Results: The adjusted hazard ratio was 1.6 for the participants with 1 APOE epsilon4 allele (95% CI: 0.9-2.7; p = 0.083) and 4.4 for those with 2 APOE epsilon4 alleles (95% CI: 1.6-12.5; p = 0.005). The increased risk did not appear to be mediated by vascular risk factors., Conclusions: The APOE epsilon4 allele is associated with an increased risk of VaD in a dose-dependent fashion and accounts for almost 20% of VaD in the population., (2010 S. Karger AG, Basel.)

Background and Objectives: To avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly., Methods: We administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm's IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses., Results: A 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of < or =82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures., Conclusions: The improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample.