Published online by Cambridge University Press: 06 July 2010
Wharton, Asthana, and Gleason review trials that have evaluated the efficacy of estrogenic therapies in the treatment and prevention of Alzheimer's disease (AD). They point out that of three large clinical trials that used conjugated equine estrogen (CEE) therapies, all reported no cognitive benefits in women with AD. This is in contrast to several small observational and uncontrolled studies that reported positive effects of estrogens on measures of mood, memory, and dementia, as well as two more recent observational trials in which long-term treatment with estradiol appeared to protect ‘at-risk’ women from AD-related pathologies (hippocampal atrophy and neuronal metabolism). In addition, two recent controlled trials evaluated the effects of transdermal estradiol on cognitive function in women with AD. These trials demonstrated rapid improvement in verbal memory, which correlated positively with plasma estradiol levels, in addition to positive effects on attention, visual memory, and semantic memory. The authors' analysis highlights the need for more research on the pharmacology of estrogenic effects on cognitive function, and in particular on the benefits of transdermal estradiol vs. oral CEE-based therapies in women with AD.