Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease.

OBJECTIVE

To examine whether estrogen replacement therapy (ERT) affects clinical and cognitive responses to tacrine in women with Alzheimer's disease (AD).

DESIGN

A 30-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial of tacrine in which a subgroup of women were receiving ERT prior to randomization.

PATIENTS

Women with mild to moderate-stage AD, at least 50 years of age, who were enrolled in the previously reported trial.

INTERVENTIONS

Randomized assignment to placebo or to one of three ascending-dosage regimens of tacrine: maximum dosages of 80 mg/d, 120 mg/d or 160 mg/d.

OUTCOME MEASURES

Alzheimer's Disease Assessment Scale-Cognitive Scale (ADASc), Clinician Interview-Based Impression of change (CIBI), Mini-Mental State Examination (MMSE), Caregiver's Impression of Change (CIC).

RESULTS

Of 318 women with evaluable data 14.5% were receiving ERT. Women completing the trial taking ERT and tacrine improved more than women not receiving ERT who were randomly assigned to tacrine or to placebo as assessed by the ADASc (p < 0.01), the CIBI (p = 0.02), the CIC (p = 0.006), and the MMSE (p = 0.07). They improved significantly on the ADASc (p = 0.01) using an intent-to-treat analysis.

CONCLUSIONS

Prior and continuing ERT may enhance response to tacrine in women with AD. Randomized trials are needed.