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Neurobiol Aging. 2014 Jul;35(7):1778.e1-8. doi: 10.1016/j.neurobiolaging.2013.12.025. Epub 2013 Dec 27.

Interaction of APOE genotype and testosterone on episodic memory in middle-aged men.

Author information

1
Department of Psychiatry, University of California, San Diego, CA, USA; Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, CA, USA. Electronic address: mspanizz@ucsd.edu.
2
Department of Psychiatry, University of California, San Diego, CA, USA; VA San Diego Healthcare System, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
3
Department of Biostatistics, St. Louis University, College for Public Health & Social Justice, St. Louis, MO, USA; Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, MO.
4
Department of Psychiatry, University of California, San Diego, CA, USA; Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, CA, USA; Department of Public Health, University of Helsinki, Helsinki, Finland.
5
Computational Science Research Center, San Diego State University, San Diego, CA, USA.
6
Department of Psychology, University of California, Davis, CA, USA.
7
Department of Psychiatry, University of Chicago, Chicago, IL, USA.
8
Department of Psychiatry, University of California, San Diego, CA, USA; Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, CA, USA.
9
Department of Psychology, Boston University, Boston, MA, USA.
10
Department of Psychiatry and Human Behavior, The Miriam Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI, USA.
11
Department of Psychiatry, University of California, San Diego, CA, USA; Twin Research Laboratory, Center for Behavioral Genomics, University of California, San Diego, CA, USA; VA San Diego Healthcare System, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.

Abstract

Age-related changes in testosterone are believed to be a key component of the processes that contribute to cognitive aging in men. The APOE-ε4 allele may interact with testosterone and moderate the hormone's association with cognition. The goals of the present study were to examine the degree to which free testosterone is associated with episodic memory in a community-based sample of middle-aged men, and examine the potential interaction between free testosterone and the APOE-ε4 allele. Data were used from 717 participants in the Vietnam Era Twin Study of Aging. Average age was 55.4 years (standard deviation = 2.5). Significant positive associations were observed between free testosterone level and verbal episodic memory, as well as a significant interaction between free testosterone and APOE-ε4 status. In ε4 carriers free testosterone was positively associated with verbal episodic memory performance (story recall), whereas no association was observed in ε4 noncarriers. Results support the hypothesis that APOE-ε4 status increases susceptibility to other risk factors, such as low testosterone, which may ultimately contribute to cognitive decline or dementia.

KEYWORDS:

APOE; Episodic memory; Gene-hormone interaction; Middle-age; Testosterone

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