Wayne State Professor Scott Moffat and his colleagues have discovered a link between low testosterone and Alzheimer's disease (AD) in older men.

"This is a big step forward in helping to understand how sex hormones affect the aging brain and body," said Moffat, the lead investigator on the study, which appears in the January 27, 2004 issue of the journal Neurology.

Moffat, an assistant professor with WSU's Institute of Gerontology and department of psychology, conducted this study in collaboration with other research scientists at the National Institute on Aging (NIA), one of the National Institutes of Health, and WSU.

However, Moffat cautions that much more research is needed before we can establish a causal relationship between low testosterone and AD.

"We still have much to learn," Moffat 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."

In this study, investigators evaluated the testosterone levels of 574 men, ages 32 to 87, who participated in the Baltimore Longitudinal Study of Aging (BLSA). They examined "free" and "total testosterone levels" measured over an average of 19 years "in relationship to subsequent diagnosis of AD." Launched in 1958, the BLSA is America's longest running scientific examination of human aging. Researchers there have measured testosterone levels in male participants since 1963.

The research team found that for every 50 percent increase in the free testosterone 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 dramatically 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.

In earlier studies, Moffat and his 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's quite possible that free testosterone has many different influences on the aging brain,"" he suggests. "The effects of some of these influences on certain types of memory loss and Alzheimer's disease, for example are just beginning to be explored.""

Other BLSA studies suggest that men older than 70 generally have lower levels of free testosterone than younger men. But while prescription testosterone replacement therapy is available, it may not be advisable for most older men because the side effects of this hormone therapy are uncertain. It is not yet known, for instance, if testosterone replacement increases the risk of prostate cancer, the second leading cause of cancer death among men. In addition, studies suggest that testosterone therapy might increase a man's risk of stroke. Carefully designed and monitored clinical trials will help to clarify the risks and benefits of testosterone therapy.