Context: Although the association between Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE-epsilon4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians.
Objective: To investigate the association between the APOE-epsilon4 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-epsilon4 allele.
Results: Compared with individuals with the APOE-epsilon3/epsilon3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-epsilon4 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-epsilon4 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-epsilon4 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-epsilon4 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.
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http://dx.doi.org/10.1001/jama.279.10.751 | DOI Listing |
Int J Geriatr Psychiatry
January 2025
Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
Background: Apolipoprotein E (ApoE) ε4 genotype is a well-known risk factor for Alzheimer's disease (AD). However, its effect on predicting cognitive decline in individuals without dementia and its association with age are unclear.
Objective: To investigate the relationship between ApoE polymorphism and risk of cognitive decline and dementia incidence in the elderly without dementia.
Nat Med
January 2025
Optimal Aging Institute and Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Although previous studies have shown that cognitive decline in Alzheimer's disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD).
Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 ( ε4) on cortical atrophy in both cohorts.
Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance.
PLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
School of Psychology, Liverpool John Moores University, Liverpool, UK.
Introduction: Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it.
Methods: In an observational study of 136 cognitively unimpaired female participants (M = 66.
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