Search

Objective. —To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). Design and Setting. —Population-based, case-control study from Rotterdam, the Netherlands, and New York City. Participants. —A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. Main Outcome Measures. —TheAPOEallele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to theAPOEϵ4 allele. Results. —Overall, patients with dementia and stroke had a higherAPOEϵ4 allele frequency than controls. Compared withAPOEe3 homozygote individuals,APOEϵ4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), whileAPOEϵ4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated withAPOEϵ4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to theAPOEϵ4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD. Conclusion. —TheAPOEϵ4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.

Background The primary effect of the apolipoprotein E e4 ( APOE e4 ) allele is on the age at onset of Alzheimer disease (AD). Objective To investigate whether the presence of the APOE e4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD). Design Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older. Setting Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico. Participants There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses. Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE e4 . Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers. Results The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE e4 allele was present for age at onset in FAD ( P = .001) but not in SAD. The age at onset in patients homozygous for the APOE e4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE e4 allele and those without an APOE e4 allele. Conclusions Apolipoprotein E e4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE e4 allele, additional genetic or environmental factors may accelerate the onset of dementia.

Objectives To reexamine the association between the apolipoprotein E ϵ4 allele (APOEϵ4) and familial Alzheimer disease (AD), and to search for novel genes that may be associated with susceptibility in Caribbean Hispanic families with a history of AD. Methods Families were identified in Caribbean Hispanic communities in the greater New York City area, the Dominican Republic, and Puerto Rico. Each family in the study cohort included at least 2 living relatives with a history of dementia. All family members underwent neuropsychological testing and medical and neurological examinations to establish the presence or absence of dementia and to specify the type of dementia. Results Over a 2½-year period, 203 families were identified. Of these, 19 families had at least 1 family member with onset of dementia before age 55 years, with 8 of the 19 families showing an association with a previously unreported presenilin mutation. Multiple cases of AD were identified in 29 families. Overall, there were 236 affected sibling pairs with AD available for analysis. The average age at onset was 74 years. The presence ofAPOEϵ4 was strongly associated with AD. Conclusions Both early-onset and late-onset familial AD occur in Caribbean Hispanics. In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated withAPOEϵ4. Future attempts to identify additional susceptibility genes should consider the effects ofAPOEϵ4.

Background Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism ( PS1-1 ) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies. Objective To genotype the PS1 intron 8 polymorphism in predominantly Hispanic families with LOAD to test for association and for linkage between this polymorphism and LOAD. Design A family-based, case-control, genetic-linkage study. Setting Predominantly Hispanic families were selected from probands who were part of a random sample of 2128 Medicare beneficiaries aged 65 years or older who were residing in the community of Washington Heights, which is located in the northern part of Manhattan, NY. Participants Fifty-one families with 103 affected family members, 67 unaffected family members, and 7 family members with other diagnoses were genotyped for the PS1 polymorphism. All patients met National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria for either probable or possible Alzheimer disease. Age was truncated at 55 years or older. Main Outcome Measures Association analyses, conditional logistic regression, and traditional linkage methods were applied to the families for the PS1 polymorphism and for the presence of the gene for apolipoprotein E ( APOE ). Results of the association and conditional logistic regression analyses of PS1 intron 8 polymorphism were subsequently adjusted for the effect of APOE-ϵ4 , sex, age, and education of each sibling. Results No association between the PS1 intron 8 polymorphism and LOAD was observed (relative risk, 0.99; 95% confidence interval, 0.3-3.4). An association between presence of the APOE-ϵ4 allele and LOAD (relative risk, 4.05; 95% confidence interval, 1.3-12.5) was observed. Conclusion We could not confirm the relationship between the PS1 intron 8 polymorphism and LOAD in this collection of families.

Context.—Although the association between Alzheimer disease (AD) and the apolipoprotein E ∊4 (APOE-∊4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians.Objective.—To investigate the association between the APOE-∊4 allele and AD in elderly African Americans, Hispanics, and whites.Design.—Prospective, population-based, longitudinal study over a 5-year period (1991-1996).Setting.—The Washington Heights–Inwood community of New York City.Participants.—A total of 1079 Medicare recipients without AD or a related disorder at baseline.Main Outcome Measures.—Risk of clinically diagnosed AD in the 3 ethnic groups and among individuals with and without an APOE-∊4 allele.Results.—Compared with individuals with the APOE-∊3/∊3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-∊4 allele was significantly increased among whites (RR, 2.5; 95% confidence interval [CI], 1.1-6.4), but not among African Americans (RR, 1.0; 95% CI, 0.6-1.6) or Hispanics (RR, 1.1; 95% CI, 0.7-1.6). In the absence of the APOE-∊4 allele, the cumulative risks of AD to age 90 years, adjusted for education and sex, were 4 times higher for African Americans (RR, 4.4; 95% CI, 2.3-8.6) and 2 times higher for Hispanics (RR, 2.3; 95% CI, 1.2-4.3) than for whites. In the presence of an APOE-∊4 allele, the cumulative risk of AD to age 90 years was similar for individuals in all 3 ethnic groups.Conclusion.—The presence of an APOE-∊4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype. These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics.

Objective. —To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the ϵ4 allele. Design. —Community-based cohort study. Setting. —East Boston, Mass. Participants. —A random sample of 578 community residents aged 65 years and older free of AD. Main Outcome Measure. —Clinical diagnosis of AD by uniform, structured evaluation. Results. —The increased risk of AD associated with the presence of the ϵ4 allele was less than that found in most family and case-control studies. Persons with the ϵ4/ϵ4 or ϵ3/ϵ4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the ϵ3/ϵ3 genotype. The ϵ4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the ϵ4 allele on risk of AD did not appear to vary with age. Conclusions. —The apolipoprotein E ϵ4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.