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

Published online by Cambridge University Press:  24 February 2014

Hugh C. Hendrie*
Affiliation:
Indiana University Center for Aging Research, Indianapolis, Indiana, USA Regenstrief Institute, Inc., Indianapolis, Indiana, USA Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA
Jill Murrell
Affiliation:
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Olusegun Baiyewu
Affiliation:
Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria
Kathleen A. Lane
Affiliation:
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
Christianna Purnell
Affiliation:
Regenstrief Institute, Inc., Indianapolis, Indiana, USA
Adesola Ogunniyi
Affiliation:
Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria
Frederick W. Unverzagt
Affiliation:
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA
Kathleen Hall
Affiliation:
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA
Christopher M. Callahan
Affiliation:
Indiana University Center for Aging Research, Indianapolis, Indiana, USA Regenstrief Institute, Inc., Indianapolis, Indiana, USA Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Andrew J. Saykin
Affiliation:
Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, Indiana, USA
Oye Gureje
Affiliation:
Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria
Ann Hake
Affiliation:
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA
Tatiana Foroud
Affiliation:
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
Sujuan Gao
Affiliation:
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
*
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.

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.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2014 

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