Testosterone and Alzheimer’s Disease Risk in Older Men

There is a paucity of data on the relationship between testosterone and Alzheimer’s disease (AD) in older men. The objective of the present study was to investigate the effects of serum total testosterone (TT), bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) levels on the subsequent risk of AD in non-demented Chinese older men. This was a one-year prospective cohort study. 153 ambulatory community-living non-demented Chinese older men, aged 55 years or over, were recruited and followed for one year. Morning serum TT, BT, and SHBG levels were measured at baseline. At one-year of follow-up, assessment for dementia and AD were performed. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. Overall, the mean age of the subjects was 72.7 (SD 6.9). 6.5% (n = 10) developed dementia (converters), all having AD. 93.5% (n = 143) did not develop dementia (non-converters). Logistic regression analysis for independent predictors of AD showed that the baseline serum BT level, systolic blood pressure (SBP) and ApoE ε4 genotype were significant independent predictors, after adjustment for age, education, BMI, fasting plasma glucose, and serum HDL-C levels. The baseline serum BT level predicted a reduced risk of AD (adjusted relative risk (RR) 0.22, 95% CI: 0.07-0.69)). Baseline SBP and ApoE ε4 genotype but not SHBG were independent risk factors, with RRs of 1.04 and 5.04 respectively. In conclusion, the serum level of bioavailable testosterone in late life predicts a lower risk of future AD development in older men.

From press release:

Low levels of the male sex hormone, testosterone, in older men is associated with the onset of Alzheimer's disease, according to research by a team that includes a Saint Louis University scientist.

"Having low testosterone may make you more vulnerable to Alzheimer's disease," said John E. Morley, M.D., director of the division of geriatric medicine at Saint Louis University and a study co-investigator. "The take-home message is we should pay more attention to low testosterone, particularly in people who have memory problems or other signs of cognitive impairment."

The study was published electronically prior to its print publication scheduled in the September issue of the Journal of Alzheimer's Disease and led by Leung-Wing Chu, M.D., who is chief of the division of geriatric medicine at Queen Mary Hospital at the University of Hong Kong.

Researchers studied 153 Chinese men who were recruited from social centers. They were at least 55 years and older, lived in the community and didn't have dementia. Of those men, 47 had mild cognitive impairment -- or problems with clear thinking and memory loss.

Within a year, 10 men who all were part of the cognitively impaired group developed probable Alzheimer's disease. These men also had low testosterone in their body tissues; elevated levels of the ApoE 4 (apolipoprotein E) protein, which is correlated with a higher risk of Alzheimer's disease; and high blood pressure.

"It's a very exciting study because we've shown that a low level of testosterone is one of the risk factors for Alzheimer's disease," Morley said.

The findings corroborate findings in previous studies of older Caucasian men that show low testosterone is associated with impaired thinking and Alzheimer's disease. They suggest that testosterone may have a protective value against Alzheimer's disease.

The next step, Morley said, is to conduct a large-scale study that investigates the use of testosterone in preventing Alzheimer's disease. Morley and his co-authors advocate studying the effectiveness of testosterone replacement in older men who have both mild memory problems and low testosterone in staving off Alzheimer's disease.