Objective
To test whether more physiologically assessed hot flashes were associated with more connectivity in the default mode network (DMN), the network of brain regions active during rest. We particularly focus on DMN networks supporting the hippocampus as this region is rich in estrogen (E) receptors (ER) and has previously been linked to hot flashes.
Design
Women underwent 24 hours of physiologic and diary hot flash monitoring, functional magnetic resonance imaging (MRI), 72 hours of sleep actigraphy monitoring, a blood draw, questionnaires, and physical measures.
Setting
University medical center.
Patient(s)
Twenty midlife women aged 40–60 years who had their uterus and both ovaries and were not taking hormone therapy (HT).
Intervention(s)
None.
Main Outcome Measure(s)
The DMN functional connectivity.
Result(s)
Controlling for age, race, and education, more physiologically-monitored hot flashes were associated with greater DMN connectivity (beta, B [SE] = 0.004 [0.002]), particularly hippocampal DMN connectivity (B [SE] = 0.005 [0.002]). Findings were most pronounced for sleep physiologic hot flashes (with hippocampal DMN, B [SE] = 0.02 [0.007]). Associations also persisted controlling for sleep, depressive symptoms, and serum E2 concentrations.
Conclusion(s)
More physiologically-monitored hot flashes were associated with more DMN connectivity, particularly networks supporting the hippocampus. Findings were most pronounced for sleep hot flashes. Findings underscore the importance of continued investigation of the central nervous system in efforts to understand this classic menopausal phenomenon.

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.