A – 92 Menstrual Milestones and Memory: Investigating Estradiol’s Influence on Cognition in Aging Women

Abstract Objective Estradiol’s neuroprotective role in modulating cognition through synaptic plasticity and neurotransmitter functioning is well-established. Postmenopausal reduction in estradiol is associated with decreased memory performance, partially due to estradiol’s impact on basal forebrain cholinergic neurons that heavily project into the hippocampus. This study examined the relationship between estradiol, timing of menarche and menopause, and verbal memory performance. Method Using data from the Nathan Kline Institute (NKI) Rockland Sample, a retrospective analysis of demographic variables, serum estradiol levels, and verbal memory (i.e., Rey Auditory Verbal Learning Test [RAVLT] Delayed Recall) was conducted with 92 postmenopausal women (age 47-71; M=59.8±6.36) who had not undergone estradiol hormone replacement therapy. Mediation analysis models examined the effect of age, age of menarche, and duration of reproductive period on postmenopausal estradiol levels and delayed verbal memory, controlling for education and vascular risk factors. Results Mediation analysis using Hayes PROCESS based on 5,000 bootstrapped samples demonstrated a significant direct effect of postmenopausal estradiol levels on delayed verbal memory (b=1.83, SE=0.90, 95% CI [-3.62, -0.378], p< 0.05), not mediated by age, age of menarche, or duration of reproductive period. Conclusion Postmenopausal estradiol levels were directly associated with verbal memory even when accounting for age, supporting how estrogen’s neuroprotective role in cognitive aging is time-sensitive rather than dependent on cumulative exposure over a lifetime. Results align with the Critical Window Hypothesis, positing that estradiol’s cognitive/protective benefits may be more pronounced when endogenous estrogen exposure occurs within a specific time frame following menopause. Monitoring estradiol fluctuations during perimenopause is necessary to better inform intervention timing.