Skip to main content
    • Aa
    • Aa

APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba

  • Hugh C. Hendrie (a1) (a2) (a3), Jill Murrell (a4), Olusegun Baiyewu (a5), Kathleen A. Lane (a6), Christianna Purnell (a2), Adesola Ogunniyi (a7), Frederick W. Unverzagt (a3), Kathleen Hall (a3), Christopher M. Callahan (a1) (a2) (a8), Andrew J. Saykin (a9), Oye Gureje (a5), Ann Hake (a10), Tatiana Foroud (a11) and Sujuan Gao (a6)...
ABSTRACT 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.


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.


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).


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.

Corresponding author
Correspondence should be addressed to: Hugh C. Hendrie, MB, ChB, DSc, Indiana University Center for Aging Research, 410 W 10th St., Suite 2000, Indianapolis, IN 46202, USA. Phone: (317) 423-5591; Fax: (317) 423-5695. Email:
Hide All
American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised. Washington, DC: American Psychiatric Assocation.
American Pychiatric Association Press (1992). ICD-10. The International Statistical Classification of Diseases and Related Health Problems: 1 and 2.
BellJ. T. et al. (2011). DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biology, 12, R10.
ChaliseP., ChickenE. and McGeeD. (2011) Baseline age effect on parameter estimates in Cox models. Journal of Statistical Computation and Simulation, 82, 17671774.
ChenC. H. et al. (2010). A comparative study to screen dementia and APOE genotypes in an ageing East African population. Neurobiol Aging, 31, 732740.
ChuangY. F. et al. (2010). Association between APOE epsilon4 allele and vascular dementia: the Cache County study. Dementia and Geriatric Cognitive Disorders, 29, 248253.
CorboR. M. and ScacchiR. (1999). Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? Annals of Human Genetics, 63, 301310.
DeegM. et al. (2008). A comparison of cardiovascular disease risk factor biomarkers in African Americans and Yoruba Nigerians. Ethnicity & Disease, 18, 427433.
DegnerJ. F. et al. (2012). DNase I sensitivity QTLs are a jamor determinant of human expression variation. Nature, 482, 390394.
EvansR. M. et al. (2000). Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology, 54, 240242.
FarrerL. A. et al. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA, 278, 13491356.
FinchC. E. and SapolskyR. M. (1999). The evolution of Alzheimer disease, the reproductive schedule, and APOE isoforms. Neurobiology of Aging, 20, 407428.
FinchC. E. and StanfordC. B. (2004). Meat-adaptive genes and the evolution of slower aging in humans. Quarterly Review of Biology, 63, 301310.
GurejeO. et al. (2006). APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians. Annals of Human Genetics, 59, 182185.
HallK. S., GaoS., EmsleyC. L., OgunniyiA. O., MorganO. and HendrieH. C. (2000). Community screening interview for dementia (CSI ‘D’); performance in five disparate study sites. International Journal of Geriatric Psychiatry, 15, 521531.
HallK. et al. (2006) Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba. Neurology, 66, 223227.
HendrieH. C. et al. (1988). The CAMDEX: a standardized instrument for the diagnosis of mental disorder in the elderly: a replication with a US sample. Journal of the American Geriatrics Society, 36, 402408.
HendrieH. C. et al. (2001). Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana. JAMA, 285, 739747.
HendrieH. et al. (2004). Alzheimer's disease, genes, and environment: the value of international studies. Canadian Journal of Psychiatry, 49, 9299.
HendrieH. C. et al. (2006). The development of a semi-structured home interview (CHIF) to directly assess function in cognitively impaired elderly people in two cultures. International Psychogeriatrics, 18, 653666.
HendrieH. et al. (2013). Homocysteine levels and dementia risk in Yoruba and African Americans. International Psychogeriatrics, 25, 18591866.
HixsonJ. E. and VernierD. T. (1990). Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. Journal of Lipid Research, 31, 545548.
KnopmanD. S., MosleyT. H., CatellierD. J. and CokerL. H. (2009). Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimers Dementia, 5, 207214.
KullerL. H. et al. (1998). Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study. Stroke, 29, 388398.
LeffondreK., TouraineC., HelmerC. and JolyP. (2013). Internal-censored time-to-event and competing risk with death: is the illness-death model more accurate than the Cox model? International Journal of Epidemiology, 42, 11771186.
MartinG. M. (1999). APOE alleles and lipophylic pathogens. Neurobiol Aging, 20, 441443.
McKhannG., DrachmanD., FolsteinM., KatzmanR., PriceD. and StadlanE. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939944.
MorrisJ. C. et al. (1989). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology, 39, 11591165.
MurrellJ. R. et al. (2006). Association of apolipoprotein E genotype and Alzheimer disease in African Americans. Archives of Neurology, 63, 431434.
OharaT. et al. (2011). Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese: the Hisayama Study. Journal of the American Geriatrics Society, 59, 10741079.
ReitzC. et al. (2013). Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E 4,and the risk of late-onset Alzheimer disease in African Americans. JAMA, 309, 14831492.
SahotaA. et al. (1997). Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent. Annals of Neurology, 42, 659661.
SawyerK., Sachs-EricssonN., PreacherK. J. and BlazerD. G. (2009). Racial differences in the influence of the APOE epsilon 4 allele on cognitive decline in a sample of community-dwelling older adults. Gerontology, 55, 3240.
StewartR., RussC., RichardsM., BrayneC., LovestoneS. and MannA. (2001). Apolipoprotein E genotype, vascular risk and early cognitive impairment in an African Caribbean population. Dementia and Geriatric Cognitive Disorders, 12, 251256.
TennessenJ. A. et al. (2012). Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science, 337, 6469.
TishkoffS. A. et al. (2009). The genetic risk structure and history of Africans and African Americans. Science, 324, 10351044.
UnverzagtF. W. et al. (2011). Incidence and risk factors for cognitive impairment no dementia and mild cognitive impairment in African Americans. Alzheimer Disease and Associated Disorders, 25, 410.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 3
Total number of PDF views: 22 *
Loading metrics...

Abstract views

Total abstract views: 240 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st October 2017. This data will be updated every 24 hours.