APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba
Open accessAbstract
BACKGROUND: There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. METHODS: In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models. RESULTS: After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). CONCLUSIONS: In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.
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The influence of the APOE-e4 allele on Alzheimer's risk may be stronger for White Americans than Black Americans.
“the influence of the APOE-e4 allele on Alzheimer's risk may be stronger for White Americans than Black Americans”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [83]
The Discussion reports that APOE ε4 increases incident Alzheimer’s risk in African Americans, but the study compares African Americans with Yoruba, not White Americans. The Introduction mentions no discernible difference between African American and Caucasian populations for cognitive decline, which is a different outcome; the claimed comparison in Alzheimer’s risk is not established. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe influence of the APOE-e4 allele on Alzheimer's risk may be stronger for White Americans than Black Americans.
“While there is some research into how the influence of genetic risk factors on Alzheimer's and other dementias may differ by race — for example, the influence of the APOE‐e4 allele on Alzheimer's risk may be stronger for White Americans than Black Americans”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [89]
The Discussion reports that APOE ε4 increases incident Alzheimer’s risk in the African American cohort. But the study compares African Americans with Yoruba participants, not White Americans, so it does not establish the claimed White–Black difference in effect strength. The Introduction’s comparison with Caucasian populations concerns cognitive decline and reports no discernible difference in effect size. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSome studies found that having the APOE-e4 allele did not increase Alzheimer's risk among Blacks, while other studies found that it significantly increased risk.
“For example, some have found that having the e4 allele did not increase risk among Blacks, [80][81][82] while other studies have found that it significantly increased risk.[83][84][85][86]”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [83]
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References 35 · Cited by 123
Research works printed but not linked: 1
- American Pychiatric Association Press 1992 ICD-10 The International Statistical Classification of Diseases and Related Health Problems: 1 and 2
- Authors
- Hendrie, H. C., Murrell, J., Baiyewu, O., Lane, K. A., Purnell, C., Ogunniyi, A., Unverzagt, F. W., Hall, K., Callahan, C. M., Saykin, A. J., Gureje, O., Hake, A., Foroud, T., & Gao, S.
- Affiliations
- Regenstrief Institute (US)
- Indiana University School of Medicine (US)
- University of Ibadan (NG)
- Indiana University Indianapolis (US)
- Corresponding author
- Hendrie, Hugh C.
- ORCID
- Venue
- International Psychogeriatrics
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 26
- Issue
- 6
- Pages
- 977-985
- ISSN
- 1041-6102 (ISSN-L)
- PMC
- PMC4012422
- OpenAlex
- W2148537480
- Cited by
- 123
- References
- 35
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 16 · 2023: 14 · 2022: 6 · 2021: 20 · 2020: 12 · 2019: 13 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 7 · 2014: 1 · 2013: 1
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Psychogeriatrics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- National Institutes of Health (UL1TR001108)
- National Institute on Aging (P30AG010133, R01AG09956, R01AG019771, P30 AG-10133, R01AG009956)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- APOE ε4, Alzheimer's disease risk, cognitive decline, African Americans, Yoruba, genetic risk factors, replication study
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Black or African American, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Nigeria, Risk Factors, Proportional Hazards Models, Genetic Predisposition to Disease, Black People, Kaplan-Meier Estimate, Apolipoprotein E4, Genotyping Techniques
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