Menopausal Vasomotor Symptoms and Brain Aging in Women

在阿尔茨海默病(AD)的自然病史早期识别认知变化的危险因素至关重要，因为 目前还没有治愈这种疾病的方法。女性患阿尔茨海默病的风险高于男性，但很少有研究表明 确定了与女性有关的疾病风险因素。更年期在妇女中是一种普遍的事件，并影响 认知和大脑健康。除了荷尔蒙的变化，更年期还伴随着血管运动。 症状(VMS)和睡眠问题。超过70%的中年女性报告患有VMS，三分之一的女性报告VMS 已经坚持了十多年，一直持续到60年代。此外，有一半的女性报告在更年期时睡眠不佳。 很少有研究研究VMS对大脑健康的影响，特别是在睡眠期间(睡眠VMS)。知情者 通过我们的新的试点工作，展示了睡眠VMS与大脑健康的联系，以及对 睡眠不良对大脑健康和AD病理的负面影响，MsBrain I研究重点关注VMS和睡眠 干扰，持续的症状与AD的危险因素有关，包括心血管疾病(CVD)。我们最初的 MsBrain I调查结果表明，客观评估的睡眠VMS(使用最先进的非卧床测量) 以及睡眠不佳(用活动记录仪测量)与认知功能差和 大脑结构和功能的不利指标。性类固醇激素不能解释这些联系。在……里面 MsBrain II，我们建议测试VMS和睡眠不良作为大脑和认知不良变化的风险因素 160名MsBrain I参与者的健康状况(目前平均年龄为60岁)。我们的主要目标是利用 纵向设计，以测试是否有更大的负担客观评估更年期症状(睡眠 VMS，睡眠不佳)在十年内评估三次，与大脑和认知能力下降有关 随着时间的推移保持健康。我们将测试雌激素和心血管疾病风险在睡眠VMS和睡眠与 大脑和认知健康。这一目标认识到认知障碍风险因素之间的复杂相互作用。 损害，重点是随着更年期而变化的因素。此外，大量的基础科学表明 更年期引起的线粒体功能变化，从而导致不利的大脑变化。我们的试点数据 发现与线粒体功能改变相关的VMS和睡眠。我们的第三个目标是测试线粒体之间的关系 线粒体功能对大脑健康的作用以及线粒体功能在VMS、睡眠和大脑健康之间的联系中的作用。至 为了实现这些目标，我们将邀请160名MsBrain I参与者回来重复对VMS和 睡眠，以及心血管危险因素评估，颈动脉超声成像，性激素测量，血液- 基于线粒体功能的测量和神经心理测试。为了推进这项科学，我们将 扩展我们的脑成像工作，利用最先进的7特斯拉(7T)磁共振成像来评估 大脑的结构和功能。这项研究的发现将确定VMS和睡眠不佳是否会 被认为是有认知能力下降风险的中年女性的标志。这项工作的最终目标是协助 早期干预的努力，以改善认知，增强大脑储备，并降低老年妇女的AD风险。

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.