AN ENRICHED-POPULATION, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER STUDY OF TACRINE AND LECITHIN IN ALZHEIMERS-DISEASE

We studied the effects of 40 and 80 mg/day of tacrine on patients with probable Alzheimer's disease (AD) in an 8-week, randomized, double-bl ind, placebo-controlled crossover trial with an enriched-population de sign. In the initial dose titration phase, an intent-to-treat analysis showed significantly more improvement with 80 mg/day of tacrine than placebo. In the subsequent crossover trial that included only 'respond ers', no significant improvement was observed with tacrine, whether or not it was given with lecithin. We found that individualized dose tit ration and enrichment strategies were not helpful and had the effect o f reducing the power of the study. In the dose titration phase of this study we found that more impaired subjects were as likely to improve as those who were less impaired, suggesting that tacrine should be fur ther investigated in more severely demented AD patients.