Combined tacrine and estrogen replacement therapy in patients with Alzheimer's disease

In light of evidence that estrogen replacement might affect cholinergic function, we examined possible effects of estrogen replacement therapy (ERT) on clinical response to the cholinesterase inhibitor tacrine in women with Alzheimer's disease (AD). In a previously reported 30-week, randomized, double-blind, placebo-controlled, multicenter clinical trial, 14.5% of 318 women with evaluable data had been receiving ERT before randomization. They were randomly assigned to receive placebo or tacrine. Women receiving ERT who were randomized to tacrine improved more than women not receiving ERT who were randomized either to tacrine or to placebo as assessed by cognitive (p < 0.01) and clinical global (p = 0.02) tests. These results provide evidence that prior and continuing ERT may enhance response to tacrine in women with AD. Furthermore, among women on ERT receiving tacrine, there tended to be greater improvement relative to placebo among those without an APOE-epsilon 4 allele. Randomized trials are needed.