International Psychogeriatrics

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

Hugh C. Hendriea1a2a3 c1, Jill Murrella4, Olusegun Baiyewua5, Kathleen A. Lanea6, Christianna Purnella2, Adesola Ogunniyia7, Frederick W. Unverzagta3, Kathleen Halla3, Christopher M. Callahana1a2a8, Andrew J. Saykina9, Oye Gurejea5, Ann Hakea10, Tatiana Forouda11 and Sujuan Gaoa6

a1 Indiana University Center for Aging Research, Indianapolis, Indiana, USA

a2 Regenstrief Institute, Inc., Indianapolis, Indiana, USA

a3 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA

a4 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

a5 Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria

a6 Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA

a7 Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria

a8 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

a9 Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, Indiana, USA

a10 Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA

a11 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA

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.

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.

(Received October 21 2013)

(Reviewed November 14 2013)

(Revised December 20 2013)

(Accepted January 16 2014)

(Online publication February 24 2014)

Key words:

  • Alzheimer disease;
  • cognitive impairment;
  • APOE ε4;
  • African Americans;
  • Yoruba

Correspondence

c1 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: hhendri@iupui.edu.