Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers

Abstract

BackgroundIdentifying risk factors for Alzheimer’s disease (AD) in women is important as women comprise two thirds of individuals with AD. Prior work links vasomotor symptoms (VMS), the cardinal menopausal symptom, with poor memory performance and with alterations in brain structure, function, and connectivity. These association are evident when VMS are monitored objectively with ambulatory skin conductance monitors. ObjectiveTo determine whether VMS are associated with AD biomarkers. Study DesignBetween 2017 and 2020 the MsBrain study enrolled 274 community-dwelling women aged 45-67 who had a uterus and at least one ovary and were late perimenopausal or postmenopausal. Key exclusion criteria included neurological disorder, surgical menopause, and recent use of hormonal or non-hormonal VMS treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess VMS. Plasma concentrations of AD biomarkers including amyloid β (Aβ) 42/40 ratio, phosphorylated tau (p-tau 181 and 231), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were measured using single molecule array (Simoa) technology. Associations between VMS and AD biomarkers were assessed via linear regression models adjusted for age, race/ethnicity, education, body mass index, apolipoprotein E4 status, and in additional models, estradiol and sleep. ResultsA total of 248 (mean age=59.06 years, 81% white, 99% postmenopausal) of enrolled MsBrain participants contributed data. Objectively-assessed VMS occurring during sleep were associated with significantly lower Aβ42/Aβ40, [B(SE)=-.0010 (.0004), p=.018, multivariable], suggestive of greater brain Aβ pathology. Findings remained significant after additional adjustments for estradiol and sleep. ConclusionsNighttime VMS may be a marker of women at risk of AD. It is yet unknown if these associations are causal.