Lifecourse stressors and trajectories of neurocognitive health across the menopausal transition

Brigham And Women'S Hospital, Boston MA

Investigators

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Abstract

Across the menopausal transition, women experience dramatic changes that extend beyond cessation of menses, including alterations that accelerate aging. Many experience neurocognitive changes, including vasomotor symptoms (VMS), sleep fragmentation, depression and anxiety symptoms, and memory and other cognitive problems, which erode quality of life and may be important female-specific risk factors for cognitive impairment, dementia, and Alzheimer’s Disease. Numerous studies have characterized genetic and behavioral risk factors for neurocognitive health in midlife, but less attention has focused on individual and, especially, neighborhood-level stressors, that can be modified. Women’s risk of dementia increases dramatically after menopause, potentially related to pathways shared with menopause-related neurocognitive symptoms: sleep problems (especially fragmentation related to VMS), mood problems (anxiety and depression), and cognitive problems (memory, learning, executive processing). Exposure to stressors across the lifespan and during the menopausal transition may account substantially for female-specific associations with the neurocognitive risk factors of dementia that commonly are reported during the menopause transition. However, few studies have addressed these relationships in depth and with longitudinal follow-up. Project A of the Brigham/Harvard ROSA SCORE will test our overall hypothesis that women with greater exposure to two important neighborhood and individual stressors – artificial light at night (ALAN) and social stress – across the lifespan will have poorer neurocognitive health in midlife, characterized by greater VMS, sleep problems, and mood symptoms and by poorer cognitive performance. Further, we will examine whether relationships of ALAN and social stressors with cognition are mediated by the presence and severity of menopausal, sleep, or mood symptoms. We will leverage Project Viva, an ongoing, highly-engaged cohort of ~800 women recruited during early pregnancy and followed >25 years since (current median age 55 years). We will use these extensive data to generate objective, geographic information systems (GIS)-based measures of our primary exposures – ALAN and social stressors – taking advantage of the high degree of spatial and temporal variability in these measures within this cohort – and supplement them with individual-level self-reported stress and sensor-based measures of light to assess the relation of exposures to longitudinal trajectories of VMS, sleep, mood, and cognitive health across the menopausal transition. This proposal capitalizes on our robust cohort of midlife women and builds on our highly successful work in the first ROSA SCORE funding cycle, now including additional innovations such as exposure to ALAN, neighborhood-level stressor exposures, and outcome trajectories across two timepoints. Project A is highly integrated in the ROSA SCORE, referring our women in our cohort to Project B, sharing neurocognitive endpoints, and working closely with the SCORE Cores.