SAN FRANCISCO— Testosterone replacement therapy improved the overall quality of life for men with mild Alzheimer’s disease, and similar, although less robust, benefits were seen in healthy elderly men given the therapy, according to Po H. Lu, PsyD, and colleagues. In addition, the investigators observed either greater improvement or less decline on measures of visual-spatial abilities and mood symptoms in men with mild Alzheimer’s disease who were treated with testosterone. The researchers presented findings from their study at the 56th Annual Meeting of the American Academy of Neurology.

A total of 47 men, 50 or older, were recruited from three University of California (Los Angeles, Irvine, and San Francisco) health centers to participate in the double-blind, placebo- controlled, randomized trial. Patients with Alzheimer’s disease met the criteria for probable Alzheimer’s disease as established by the National Institute of Neurological and Communication Disorders and Stroke (now called the National Institute of Neurological Disorders and Stroke)/Alzheimer’s Disease and Related Disorders Association. Healthy controls were recruited through general advertisement and university-based clinics and showed no evidence of dementia according to DSM-IV criteria. All subjects had a Mini-Mental State Examination score of 15 or greater, had no history of psychiatric or a non-Alzheimer’s disease related neurologic illness, and were stable on concomitant medication for one month prior to starting study medication. Written, informed consent was obtained from all subjects prior to enrollment. A complete medical and psychiatric history was taken, and subjects underwent physical, neurologic, laboratory, and cognitive screening.

TESTOSTERONE VERSUS PLACEBO

All participants were randomized to receive either testosterone or placebo treatment. Testosterone, 75 mg, was provided in the form of 1% hydroalcoholic dermal gel (T-gel) applied daily to three different sites after showering. The placebo group performed the same application with placebo gel. The treatment gel phase lasted 24 weeks, and all participants returned on weeks 4 and 12 for monitoring of treatment side effects, intercurrent illness, and compliance. Cognitive and mood outcome measures were administered at baseline, prior to randomization, and repeated at the end of the study.

Cognitive outcome measures included the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, the California Verbal Learning Test, the Beery Visual-Motor Integration Test, the Judgment of Line Orientation, and the Block Design Subtest from the Wechsler Adult Intelligence Scale-Revised. Mood outcome measures consisted of the Neuropsychiatric Inventory, the Beck Depression Inventory, and the Quality of Life Scale.

IMPROVED QUALITY OF LIFE

Sixteen patients with mild Alzheimer’s disease and 22 control subjects completed the study and were included in the analyses. The researchers found that the testosterone-treated Alzheimer’s disease group obtained a significantly higher score on the Quality of Life Scale, as assessed by their caregivers, than did their placebo-treated counterparts.

“Within-group analysis of the change in scores revealed that the Quality of Life score for the placebo subjects declined significantly from baseline, while a robust, though nonsignificant, improvement was observed for the testosterone-treated group,” stated the investigators. “A divergent trajectory of the Quality of Life outcome from baseline accounted for the significant between-group differences. A similar trend was seen in the healthy control sample, but the group difference narrowly missed significance,” reported Dr. Lu, an Assistant Professor in the Department of Neurology, University of California, Los Angeles, School of Medicine.

According to the remaining outcome measures, greater improvement or less decline on measures of visual-spatial abilities and mood symptoms was observed with testosterone-treated men with Alzheimer’s disease, but the group differences did not reach statistical significance. Patients with Alzheimer’s disease who were treated with placebo displayed significant decline on the Beery Visual-Motor Integration Test—a measure of visual-spatial construction—at the end of the study, while the testosterone group performed at near baseline levels on this task. No significant treatment group differences were detected on any of the outcome measures in the healthy control subjects.

—Colby Stong

Suggested Reading
Bremner WJ. Testosterone tied to mental function. But questions about the benefits and risks of testosterone therapy persist. Health News. 2004;10:14-15.
Paoletti AM, Congia S, Lello S, et al. Low androgenization index in elderly women and elderly men with Alzheimer’s disease. Neurology. 2004;62:301-303.
Petanceska SS. Age-associated androgen deficiency and Alzheimer’s disease: a case in the making? J Alzheimers Dis. 2003;5:271-273.

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