Background
Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors.
Objective
This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers.
Study Design
Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid β 42–to–amyloid β 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep.
Results
A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid β 42/amyloid β 40, (beta, −.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid β pathology. The findings remained significant after additional adjustments for estradiol and sleep.
Conclusion
Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.

INTRODUCTION Disrupted rest-activity rhythms (RARs) have been linked to poorer cognitive function and Alzheimer’s disease (AD) biomarkers. Here we extend this work to midlife women, who commonly experience menopause-related sleep and cognitive problems. METHODS One hundred ninety-four postmenopausal participants underwent a neuropsychological evaluation, 72 h of wrist actigraphy generating RAR variables, and a blood draw to measure AD biomarkers: phosphorylated tau (p-tau181, p-tau231) and amyloid beta (Aβ40, Aβ42). RESULTS Lower interdaily stability (IS) and relative amplitude (RA) and higher interdaily variability (IV) and least active 5 h (L5) were associated with worse processing speed, independent of sleep. Adjustment for sleep significantly attenuated the associations of RA with memory. Lower RA was associated with higher p-tau231 level, independent of sleep. Further adjustment for menopause-related factors modestly accounted for the associations between RAR, cognitive measures, and AD biomarkers. DISCUSSION Weaker RAR, particularly RA, was associated with worse cognitive functions, and higher AD biomarkers levels, possibly linking RAR with AD pathology in women. Highlights Lower rhythm stability and robustness and higher fragmentation were associated with worse processing speed. Lower robustness was associated with higher levels of phosphorylated tau-231. Menopause factors did not attenuate the association between rest-activity rhythms and cognitive function.