Sci. Aging Knowl. Environ., 7 January 2004
Vol. 2004, Issue 1, p. nf3
[DOI: 10.1126/sageke.2004.1.nf3]


Weak of Body, Weak of Mind?

Dwindling testosterone concentrations in elderly men increase risk of Alzheimer's disease

Mitch Leslie

SCOTTSDALE, ARIZONA--Falling testosterone concentrations turn older men's abs to flab and can reduce their sex life to memories. A new study reveals that the hormone's decline could prime men for one of aging's most dreaded scourges. The lower a man's concentration of blood testosterone, the more likely he is to develop Alzheimer's disease (AD), according to research presented here on 12 December at the Phoenix Conference on Longevity Health Sciences. The results support preliminary studies suggesting that testosterone treatment eases the brain-destroying disease.

The amount of testosterone in a man's blood peaks during his 30s (see "More Than a Hot Flash"), and a number of studies have linked waning testosterone concentrations to decreasing mental acuity. For example, in 2002 neuropsychologist Scott Moffat of Wayne State University in Detroit, Michigan, and colleagues reported their analysis of 10 years' worth of data from participants in the Baltimore Longitudinal Study of Aging, a project that has tracked the health of people of various ages since 1958. Moffat and colleagues found that higher blood testosterone concentrations translated into better scores on several cognitive tests. Other work implicates testosterone decreases in AD. Several small studies have documented increased mental sharpness in AD patients after testosterone treatment. Furthermore, a 2003 paper indicated that castrated rats pump out more {beta} amyloid, the brain-clogging protein that accumulates in AD, and injections of a version of testosterone diminished the protein's production. Moffat and colleagues sought a stronger link between slumping testosterone concentrations and AD by studying men in the Baltimore aging study who had the disease.

They analyzed blood samples drawn 2 years before disease diagnosis. Almost half of the testosterone in the blood clings to a bulky carrier protein and can't enter cells to perform its job. So the researchers calculated a value called the free testosterone index (FTI), an indicator of how much hormone is available for cells to use. Men who developed AD had FTIs that were 40% lower than those of cognitively normal men. The researchers then checked blood samples taken 5 and 10 years before diagnosis and found the same pattern: The higher the FTI, the lower the risk of developing AD. However, the findings don't clarify whether declining testosterone concentrations cause or herald AD.

Further work on healthy men in the Baltimore study suggests that the hormone shields the hippocampus, a brain region that is crucial for making memories and that deteriorates in AD. The researchers scrutinized positron emission tomography scans, which gauge the activity of different parts of the brain by measuring blood flow. The higher the FTI, the greater the blood flow in the hippocampus. Overall, the evidence "suggests a possible neuroprotective role for testosterone," Moffat said at the meeting.

The work presents "an intriguing finding that deserves further study," says William Bremner, an endocrinologist at the University of Washington, Seattle. He cautions that scientists can't make definitive pronouncements about testosterone's impact on AD--and its safety--without a large, long-term study of its effects in older men. He envisions research analogous to the Women's Health Initiative study of hormone replacement therapy. Elderly men will have to wait to find out if testosterone can safely bulk up their brains as well as their muscles.

January 7, 2004
  1. S. D. Moffat, Testosterone and cognition. Phoenix Conference on Longevity Health Sciences, 11-14 December 2003, Scottsdale, Arizona. [Meeting Web Site]
Citation: M. Leslie, Weak of Body, Weak of Mind? Sci. Aging Knowl. Environ. 2004 (1), nf3 (2004).

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