A prospective, observational study indicates that older men with low levels of free testosterone may have a higher risk for Alzheimer's disease, according to an article in the January 27^th issue of the journal Neurology.

"Our finding that low free testosterone might be associated with an increased risk of developing of Alzheimer's disease 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, Ph.D., senior author of the study.

The American researchers evaluated the testosterone levels of 574 men, ages 32 to 87 years who were participants in a longitudinal study on aging. The investigators examined free and total testosterone levels -- measured over an average of 19 years -- in relationship to subsequent diagnosis of Alzheimer's disease. Over time, 54 of the 574 men were diagnosed with the disease.

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 for the disease. Although overall free testosterone levels fell over time, these levels dropped more precipitously in the men who later developed the disease. In fact, at the end of the study, men who were diagnosed with Alzheimer's disease, on average, had about half the level of circulating free testosterone as men who didn't develop the disease. In some cases, the decreases in free testosterone levels associated with the disease were detected up to a decade before diagnosis.

Previously, the same research group had 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," 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 Alzheimer's disease -- are just beginning to be explored."

"We still have much to learn," Resnick added. "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."

A multi-disciplinary panel supported by the National Institutes of Health is evaluating whether to begin small-scale clinical trials to determine the efficacy of testosterone in older men with low free testosterone levels. Until carefully designed and monitored clinical trials are conducted, the risks and benefits of testosterone therapy for most men who do not have extreme deficiencies of the hormone will remain largely unknown.