Interaction between testosterone and apolipoprotein E epsilon4 status on cognition in healthy older men.
BACKGROUND
Reduced testosterone levels have been implicated as a potential causative factor in cognitive decline with older age. Men who possess the apolipoprotein E (APOE) epsilon4 allele have an increased risk of developing Alzheimer's disease; however, no studies have examined whether the influence of testosterone on cognition in healthy older men may be modulated by this genetic predisposition.


OBJECTIVE
The objective of the study was to investigate the association between serum testosterone concentrations and cognitive performance in healthy older men, taking into account APOE epsilon4 status.


METHODS
This was a cross-sectional study conducted from 2003 to 2004.


METHODS
The study population consisted of community-dwelling males residing in Perth, Western Australia.


METHODS
Healthy men over 55 yr, free of cognitive impairment and dementia (n = 45), were included in the study.


METHODS
Participants had fasting early morning blood samples for testosterone and SHBG 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 epsilon4 on general cognition (P = 0.01) and executive functioning, working memory, and attention (P < 0.01). Higher levels of FT were associated with better general cognition in non-epsilon4 carriers (P = 0.01). By contrast, in epsilon4 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 Alzheimer's disease, 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 epsilon4 status.
Burkhardt
Melanie S
MS
School of Psychology, Murdoch University, Murdoch, Western Australia 6150, Australia.
Foster
Jonathan K
JK
Clarnette
Roger M
RM
Chubb
S A Paul
SA
Bruce
David G
DG
Drummond
Peter D
PD
Martins
Ralph N
RN
Yeap
Bu B
BB
D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood*; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012016:Reference Values; D013739:Testosterone / Q000097:blood*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D013739:Testosterone