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.

Sleep disturbance is common among midlife women. Poor self-reported sleep characteristics have been linked to cerebrovascular disease and dementia risk. However, little work has considered the relation of objectively assessed sleep characteristics and white matter hyperintensities (WMHs), a marker of small vessel disease in the brain. Among 122 midlife women, we tested whether women with short or disrupted sleep would have greater WMH, adjusting for cardiovascular disease (CVD) risk factors, estradiol, and physiologically assessed sleep hot flashes.We recruited 122 women (mean age = 58 years) without a history of stroke or dementia who underwent 72 h of actigraphy to quantify sleep, 24 h of physiologic monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH; phlebotomy, questionnaires, and physical measures (blood pressure, height, and weight). Associations between actigraphy-assessed sleep (wake after sleep onset and total sleep time) and WMH were tested in linear regression models. Covariates included demographics, CVD risk factors (blood pressure, lipids, and diabetes), estradiol, mood, and sleep hot flashes.Greater actigraphy-assessed waking after sleep onset was associated with more WMH [B(SE) = .008 (.002), p = 0.002], adjusting for demographics, CVD risk factors, and sleep hot flashes. Findings persisted adjusting for estradiol and mood. Neither total sleep time nor subjective sleep quality was related to WMH.Greater actigraphy-assessed waking after sleep onset but not subjective sleep was related to greater brain WMH among midlife women. Poor sleep may be associated with brain small vessel disease at midlife, which can increase the risk for brain disorders.

Objectives 
Whereas some work links trauma exposure to poor subjective sleep quality, studies largely rely upon limited trauma measures and self-reported sleep at one time point. It is unknown whether trauma is related to persistent poor sleep, whether associations differ based on childhood versus adulthood trauma, and whether trauma exposure is related to poorer objectively assessed sleep. We tested whether childhood or adult trauma associated with persistent poor objectively and subjectively measured sleep at two time points in midlife women.
Methods 
One hundred sixty-seven women aged 40-60 at baseline were assessed twice 5 years apart. At baseline, women reported childhood trauma (Child Trauma Questionnaire), adult trauma (Brief Trauma Questionnaire), demographics, depressive symptoms, apnea symptoms, and medical history, and provided physical measures. At both visits, women completed 3 days of actigraphy (total sleep time [TST], wake after sleep onset [WASO]) and reported sleep quality (Pittsburgh Sleep Quality Index). Relations of childhood and adult trauma exposure, respectively, with persistent poor sleep at both baseline and follow-up visits (TST [30 minutes], Pittsburgh Sleep Quality Index [>5]) were assessed in logistic regression models, adjusted for age, race/ethnicity, education, body mass index, sleep medications, nightshift work, apnea, depressive symptoms, vasomotor symptoms, and alcohol use.
Results 
Childhood trauma was related to persistent high WASO (odds ratio [95% confidence interval] = 2.16 [1.04-4.50], P = 0.039, multivariable). Adult trauma was related to persistent poor sleep quality (odds ratio [95% confidence interval] = 2.29 [1.07-4.93], P = 0.034, multivariable). Trauma was unrelated to persistent short TST.
Conclusions 
Childhood and adult trauma, respectively, were related to persistent poor objective sleep continuity and subjective sleep quality in midlife women, independent of risk factors.

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.