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This version published online on December 20, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1072
A more recent version of this article appeared on March 1, 2006
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Submitted on May 13, 2005
Accepted on December 8, 2005

Interaction between testosterone and APOE {epsilon}4 status on cognition in healthy older men

Melanie S. Burkhardt, Jonathan K. Foster, Roger M. Clarnette, S. A. Paul Chubb, David G. Bruce, Peter D. Drummond, Ralph N. Martins*, and Bu B. Yeap

School of Psychology, Murdoch University, Murdoch, Western Australia; Sir James McCusker Alzheimer's Disease Research Unit, School of Exercise, Biomedical & Health Sciences, Edith Cowan University, and School of Psychiatry & Clinical Neurosciences, University of Western Australia, c/o Hollywood Private Hospital, Nedlands, Western Australia; Neurosciences Unit, Health Department of Western Australia; Department of Geriatric Medicine, Fremantle Hospital, Fremantle, Western Australia; Department of Biochemistry, Fremantle Hospital, Fremantle, Western Australia; School of Medicine & Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia; Department of Endocrinology & Diabetes, Fremantle Hospital, Fremantle, Western Australia

* To whom correspondence should be addressed. E-mail: r.martins{at}ecu.edu.au.

Context. Reduced testosterone levels have been implicated as a potential causative factor in cognitive decline with older age. Men who possess the apolipoprotein E (APOE) {epsilon}4 allele have an increased risk of developing Alzheimer's disease (AD), however no studies have examined whether the influence of testosterone on cognition in healthy older men may be modulated by this genetic predisposition.

Objective. To investigate the association between serum testosterone concentrations and cognitive performance in healthy older men, taking into account APOE {epsilon}4 status.

Design. Cross-sectional study conducted from 2003 to 2004.

Setting. Community dwelling males residing in Perth, Western Australia.

Participants. Health men over 55 yr, free of cognitive impairment and dementia (n = 45).

Main outcome measures. Participants had fasting early morning blood samples for testosterone and sex hormone binding globulin and were assessed for mood as well as indices of general cognition, verbal and visual memory, executive functioning, working memory and attention.

Results. There was a significant interaction between calculated free testosterone (FT) and APOE {epsilon}4 on general cognition (P = 0.01), and on executive functioning, working memory and attention (P < 0.01). Higher levels of FT were associated with better general cognition in non{epsilon}4 carriers (p=0.01). By contrast, in {epsilon}4 carriers higher FT levels were associated with lower scores on tests of executive functioning, working memory and attention (P = 0.02). In men at increased risk for AD, higher testosterone levels were not associated with better cognitive function.

Conclusions. Cross-sectional and prospective studies of testosterone and cognition in older men should take into account APOE {epsilon}4 status.
Key words: healthy men • testosterone • APOE genotype • cognition






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