Menopausal Vasomotor Symptoms and Brain Aging in Women

点击翻译按钮获取中文摘要

Identifying risk factors for cognitive change early in the natural history of Alzheimer's disease (AD) is critical, as there is yet no cure for the disease. The lifetime risk of AD is higher in women than men, yet few studies have identified female-related risk factors for the disease. The menopause is a universal event in women and affects cognitive and brain health. In addition to hormonal changes, the menopause is accompanied by vasomotor symptoms (VMS) and sleep problems. Over 70% of midlife women report VMS, and for a third of women, VMS are persistent for over a decade, well into the 60s. Further, half of women report poor sleep at menopause. Few studies have examined the effect of VMS on brain health, particularly during sleep (sleep VMS). Informed by our novel pilot work showing links of sleep VMS to brain health and the growing understanding of the negative effect of poor sleep on brain health and AD pathology, the MsBrain I study focused on VMS and sleep disturbance, persistent symptoms tied to risk factors for AD including cardiovascular disease (CVD). Our initial MsBrain I findings indicate that objectively-assessed sleep VMS (measured with state-of-the-art ambulatory monitors) as well as poor sleep (measured with actigraphy) are associated with worse cognitive function and adverse indicators of brain structure and function. Sex steroid hormones do not explain these associations. In MsBrain II, we propose to test VMS and poor sleep as risk factors for adverse changes in brain and cognitive health among 160 MsBrain I participants (current mean age=60 years). Our primary aim is to leverage a longitudinal design to test whether a greater burden of objectively-assessed menopausal symptoms (sleep VMS, poor sleep) assessed up to three times over ten years is associated with declines brain and cognitive health over time. We will test the role of estrogens and CVD risk in the relationships of sleep VMS and sleep to brain and cognitive health. This aim recognizes the complex interplay among risk factors for cognitive impairment, with a focus on factors that change with menopause. Further, a wealth of basic science shows menopause-induced changes in mitochondrial function that contribute to adverse brain changes. Our pilot data finds VMS and sleep related to altered mitochondrial function. Our third aim tests the relations of mitochondrial function to brain health and the role of mitochondrial function in links between VMS, sleep, and brain health. To achieve these aims, we will invite 160 MsBrain I participants back to repeat objective assessments of VMS and sleep, as well as CVD risk factor assessment, carotid ultrasound imaging, sex hormone measurement, blood- based measures of mitochondrial function, and neuropsychological testing. To advance this science, we will extend our brain imaging work to leverage state-of-the-art 7 Tesla (7T) magnetic resonance imaging to assess brain structure and function. Findings from this study will determine whether VMS and poor sleep can be identified as markers for midlife women at risk of cognitive decline. The ultimate goal of this work is to assist in early intervention efforts to improve cognition, enhance brain reserve, and reduce AD risk in aging women.