Older men with lower levels of free, or unbound, testosterone circulating in their bloodstreams could be at higher risk of developing Alzheimer's disease (AD) than their peers, according to new research. This prospective observational study is believed to be the first to associate low circulating blood levels of free testosterone with AD years before diagnosis. The study appears in the journal Neurology. The study was conducted by investigators at the National Institute on Aging (NIA) and scientists at other institutions supported by the NIA. "Our finding that low free testosterone might be associated with an increased risk of developing AD is a step forward in helping to understand the possible effects of sex hormones on the aging brain and other parts of the body," said Susan Resnick, an investigator in the NIA's Laboratory of Personality and Cognition.
Dr. Resnick, however, cautions that much more research is needed before scientists can establish a causal relationship between low testosterone and AD. "Even if a relationship between AD and levels of free testosterone in the bloodstream is confirmed, we are very far away from knowing if hormonal therapy or any other intervention could safely prevent AD," she said.
Dr. Resnick, Scott Moffat and their colleagues evaluated the testosterone levels of 574 men, ages 32 to 87. The investigators examined free and total testosterone levels-measured over an average of 19 years-in relationship to subsequent diagnosis of AD. Based on physical, neurological and neuropsychological exams, 54 of the 574 men were diagnosed with AD.
The research team found that for every 50 percent increase in the free testosterone index in the bloodstream, there was about a 26 percent decrease in the risk of developing AD. Although overall free testosterone levels fell over time, these levels dropped more precipitously in those men who later developed AD. In fact, at the end of the study, men who were diagnosed with AD, on average, had about half the levels of circulating free testosterone as men who didn't develop the disease. In some cases, the drop-offs in free testosterone levels associated with AD were detected up to a decade before diagnosis.
Previously, Dr. Resnick and her colleagues found that older men with high levels of circulating free testosterone have better visual and verbal memory and perform spatial tasks more adeptly than their peers.
"It is quite possible that circulating free testosterone has a broad range of influences on the aging brain," Dr. Resnick said. "The effects of some of these influences - such as the role of testosterone in the development of certain types of memory loss and AD - are just beginning to be explored."
Other studies suggest that many men older than 70 have low levels of free testosterone compared to younger men. But while prescription testosterone replacement therapy is available, it may not be advisable for most older men because many effects of hormone therapy remain unclear.
"We still have much to learn," Dr. Resnick said. "For now, testosterone therapy should not be considered an option for older men seeking to reduce their risk of Alzheimer's disease or to improve their memory and cognitive performance in general."
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