Free testosterone and risk for Alzheimer disease in older men.
OBJECTIVE
To investigate the relationships between age-associated decreases in endogenous serum total testosterone (T) and a free T index (FTI) in men and the subsequent development of Alzheimer disease (AD).


METHODS
The authors used a prospective, longitudinal design with follow-up in men since 1958. Participants were from the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample with baseline ages of 32 to 87 years. All subjects were free of AD at baseline T assessment. Five hundred seventy-four men assessed at multiple time points were followed for a mean of 19.1 years (range, 4 to 37 years). Diagnoses of AD were based on biennial physical, neurologic, and neuropsychological evaluations.


RESULTS
Diagnosis of AD was associated inversely with FTI by itself and after adjustments for age, education, smoking status, body mass index, diabetes, any cancer diagnoses, and hormone supplements. In separate analyses, total T and sex hormone binding globulin were not significant predictors after adjustment with covariates. Increases in the FTI were associated with decreased risk of AD (hazard ratio = 0.74; 95% CI = 0.57 to 0.96), a 26% decrease for each 10-nmol/nmol FTI increase.


CONCLUSIONS
Calculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. Future research may determine whether higher endogenous free testosterone levels offer protection against a diagnosis of Alzheimer disease in older men.
Moffat
S D
SD
Laboratory of Personality and Cognition, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.
Zonderman
A B
AB
Metter
E J
EJ
Kawas
C
C
Blackman
M R
MR
Harman
S M
SM
Resnick
S M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology; D015142:Baltimore / Q000453:epidemiology; D015897:Comorbidity; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood* / Q000172:deficiency
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone