Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study.
OBJECTIVE
Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.


METHODS
Community-based, cross-sectional study of 3369 men aged 40-79 years.


METHODS
Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE(2)) and 5alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE(2) were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.


RESULTS
Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 micromol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.


CONCLUSIONS
Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.
Lee
David M
DM
arc Epidemiology Unit, Department of Medicine, Manchester Academic and Health Sciences Centre, Manchester Royal Infirmary, The University of Manchester, Grafton Street, Manchester, UK.
Ulubaev
Aslan
A
Tajar
Abdelouahid
A
Pye
Stephen R
SR
Pendleton
Neil
N
Purandare
Nitin
N
O'Neill
Terence W
TW
O'Connor
Daryl B
DB
Labrie
Fernand
F
Platt
Hazel
H
Payne
Debbie
D
Bartfai
Gyorgy
G
Boonen
Steven
S
Casanueva
Felipe F
FF
Finn
Joseph D
JD
Forti
Gianni
G
Giwercman
Aleksander
A
Han
Thang S
TS
Huhtaniemi
Ilpo T
IT
Kula
Krzysztof
K
Lean
Michael E J
ME
Punab
Margus
M
Silman
Alan J
AJ
Vanderschueren
Dirk
D
Wu
Frederick C W
FC
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011944:Receptors, Androgen / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats / Q000235:genetics*
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol