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Maki reviews randomized clinical trials of testosterone in older men, in which outcomes are based on standard neuropsychological measures or functional brain imaging with positron emission tomography. Her focus is on verbal memory, where deficits may predict the development of Alzheimer's disease (AD). Findings from these clinical studies are contradictory and sometimes confusing. Available evidence, however, suggests improvement of verbal memory, as long as testosterone therapy leads to moderate (but not large) increases in concentrations of estradiol or total testosterone. Maki believes estradiol may be a key determinant. For elderly men from the Baltimore Longitudinal Study of Aging, results of positron emission tomography link higher levels of testosterone to increased activity in brain areas involved in higher-order cognitive function. Of note, supraphysiological exogenous testosterone in one study was associated with decreased hippocampal activity and decreased verbal memory. Further research may help to understand more fully the impact of testosterone on brain function and the mechanisms by which testosterone can lead to beneficial and detrimental cognitive effects.