Menopausal Vasomotor Symptoms and Brain Aging in Women

阿尔茨海默病（AD）是美国痴呆症的主要原因。妇女特别 受AD影响。与男性相比，女性AD的患病率更高， 载脂蛋白（APOE）-ε4等位基因，以及诊断为轻度认知障碍后认知功能更快下降 损伤或AD。AD的神经病理学特征始于中年，并且随着年龄的增长， 有证据表明，需要更好地了解自然界早期认知变化的中年风险因素， AD的历史然而，很少有研究探讨性别特异性中年风险因素。更年期是一个 关键的中年过渡影响女性健康的多个方面，包括大脑和心血管 结果。临床研究表明，主观记忆的抱怨， 在标准化记忆测试中的表现，以及女性在更年期过渡时的大脑功能。 动脉粥样硬化加速累积和关键心血管疾病（CVD）风险因素恶化 在这段时间也很常见。这些大脑和心血管的变化不仅仅是由于衰老。 此外，超过70%的中年妇女报告绝经期血管痉挛症状（VMS）;三分之一的妇女， 经常或持续超过十年。长期以来，VMS被认为仅仅是一个生活质量问题， 但最近的研究结果对这一假设提出了质疑。最新证据显示 VMS的生理测量表明，VMS可能与较差的认知功能有关， 大脑结构和功能的不利变化。一项平行的研究将VMS与不利的CVD风险联系起来 因子谱和更大的亚临床CVD。在拟议的研究中，我们将测试是否更频繁或 持续性VMS与不良的结构和功能性脑结果以及较差的认知功能相关。 功能我们将测试心血管疾病危险因素和亚临床心血管疾病在这些关联中的作用， 考虑到睡眠、消极情绪和雌二醇浓度的作用。最后，我们将检测APOE状态， VMS-cognition和brain relations的调节者。我们将在230名妇女的样本中回答这些问题 从一组中年妇女中招募，这些妇女没有心血管疾病和痴呆，她们接受了详细的 他们的VMS的生理特征以及他们的激素，睡眠和CVD风险概况。我们将 邀请队列返回，重复VMS的动态生理测量; 亚临床CVD（颈动脉内膜中层厚度）;睡眠活动图评估;以及CVD的血液标志物 危险因素和雌二醇。我们还将扩大电池，包括认知测试; APOE基因分型; 功能和结构脑成像。这项研究的结果有可能将VMS确定为女性- 可以识别中年女性认知能力下降风险的特定标志物。这项工作最终可能有助于 早期干预努力，以改善认知能力，增强大脑储备，降低女性患AD的风险。

Alzheimer's disease (AD) is the leading cause of dementia in the United States. Women are particularly affected by AD. Compared to men, women have a higher prevalence of AD, higher risk of AD with the apolipoprotein (APOE)-ε4 allele, and a more rapid decline in cognition following diagnosis of mild cognitive impairment or AD. The neuropathological hallmarks of AD are laid down beginning at midlife, and increasing evidence supports the need to better understand midlife risk factors for cognitive change early in the natural history of AD. However, few studies have examined sex-specific midlife risk factors. The menopause is a critical midlife transition affecting multiple aspects of women's health, including brain and cardiovascular outcomes. Clinical studies show small but significant decrements in subjective memory complaints, performance on standardized memory tests, and brain function as women transition through the menopause. Accelerated accumulation of atherosclerosis and worsening of key cardiovascular disease (CVD) risk factors are also common during this time. These brain and cardiovascular changes are not due to aging alone. Further, over 70% of midlife women report menopausal vasomotor symptoms (VMS); for a third of women they are frequent or persistent for over a decade. VMS have long been believed to be solely a quality of life issue, but recent findings have called this assumption into question. Emerging evidence with state-of-the-art physiologic measures of VMS suggests that VMS may be associated with poorer cognitive function and adverse changes in brain structure and function. A parallel line of research links VMS to an adverse CVD risk factor profile and greater subclinical CVD. In the proposed research we will test whether more frequent or persistent VMS are associated with adverse structural and functional brain outcomes and poorer cognitive function. We will test the role of CVD risk factors and subclinical CVD in these associations, while additionally considering the role of sleep, negative mood, and estradiol concentrations. Finally, we will test APOE status as a moderator of VMS-cognition and brain relations. We will address these questions in a sample of 230 women recruited from an established cohort of midlife women free of CVD and dementia who have undergone detailed physiologic characterization of their VMS as well as of their hormonal, sleep, and CVD risk profiles. We will invite the cohort back to repeat ambulatory physiologic measurement of VMS; ultrasound measures of subclinical CVD (carotid intima media thickness); actigraphic assessment of sleep; and blood markers of CVD risk factors and estradiol. We will also expand the battery to include cognitive testing; APOE genotyping; and functional and structural brain imaging. Findings from this study have the potential to identify VMS as a female- specific marker that can identify midlife women at risk of cognitive decline. This work may ultimately assist in early intervention efforts to improve cognition, enhance brain reserve, and reduce risk for AD among women.