BackgroundThe tauopathy inhibitor, davunetide shows sex-dependent efficacy in women suffering from progressive supranuclear palsy. Extending these findings to prodromal Alzheimer’s disease, we submitted a double-blind, placebo-controlled, 12 weeks/16 weeks follow-up, davunetide clinical trial results in amnestic mild cognitive impairment (ClinicalTrials.gov ID NCT00422981), to a sex-dependent analysis.MethodsOne hundred forty-four individuals, separated into eight groups (1:2 placebo—and 2 doses, 5 mg davunetide/daily or 15 mg davunetide/twice-daily, with matching placebo intranasal volumes), were evaluated.ResultsSignificant dose-dependent cognitive increases were observed in men compared to women with a test of delayed (12 ss) visual matching to the sample. In a test of semantic working memory and attention (digit span), women showed a significant low-dose placebo effect, ensuing in a high dose significant davunetide improvement, over the matched placebo. Correlating anxiety with cognition showed sex-opposing results, with women depicting significant anxiety correlations with delayed matching to sample.DiscussionIn conclusion, sex-specific prodromal Alzheimer’s drug development is encouraged, with davunetide playing a lead initiative role.