Menopausal Vasomotor Symptoms and Brain Aging in Women

女性更年期血管舒缩症状和大脑老化

• 批准号: 9148629
• 负责人: PAULINE M MAKI
• 金额: $ 373.02万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9148629
• 关键词: Accounting; Address; Adult; Affect; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Ambulatory Monitoring; Apolipoproteins; Atherosclerosis; Back; Benign; Blood; Brain; Brain imaging; Cardiovascular Diseases; Cardiovascular system; Clinical Research; Cognition; Cognitive; Cognitive aging; Data; Dementia; Development; Diagnosis; Early Intervention; Episodic memory; Estradiol; Female; Frequencies; Functional disorder; Genotype; Health; High Prevalence; Hippocampus (Brain); Hormonal; Hormonal Change; Hot flushes; Hyperactive behavior; Impaired cognition; Incidence; Individual Differences; Inflammation; Insulin Resistance; Life; Link; Lipids; Measurement; Measures; Memory; Menopausal Symptom; Menopause; Moods; Natural History; Night Sweating; Outcome; Patient Self-Report; Performance; Physiological; Prefrontal Cortex; Prospective Studies; Quality of life; Recruitment Activity; Reporting; Research; Rest; Risk; Risk Factors; Role; Sampling; Sex Characteristics; Sleep; Speed; Staging; Structure; Symptoms; Testing; Time; Ultrasonography; United States; Vasomotor; White Matter Hyperintensity; Woman; Women' s Health; Work; adverse outcome; aging brain; associated symptom; brain health; cardiovascular disorder risk; cognitive change; cognitive function; cognitive performance; cognitive testing; cohort; cost; executive function; high risk; improved; intimal medial thickening; men; middle age; mild cognitive impairment; modifiable risk; negative mood; neuropsychological; processing speed; sex

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.

阿尔茨海默病（AD）是美国痴呆症的主要原因。女性尤其 受 AD 影响。与男性相比，女性 AD 患病率更高，AD 风险也更高 载脂蛋白 (APOE)-ε4 等位基因，以及轻度认知诊断后认知能力更快下降 损伤或AD。 AD 的神经病理学特征始于中年，并逐渐增加 证据支持需要更好地了解中年认知变化的危险因素 公元的历史。然而，很少有研究探讨特定性别的中年危险因素。更年期是一个 关键的中年转变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抱怨有小幅但显着的下降， 标准化记忆测试的表现，以及女性在更年期过渡时的大脑功能。 动脉粥样硬化的加速积累和心血管疾病 (CVD) 关键危险因素的恶化 这段时间也很常见。这些大脑和心血管的变化不仅仅是衰老造成的。 此外，超过 70% 的中年女性报告有更年期血管舒缩症状 (VMS)；对于三分之一的女性来说 经常发生或持续十多年。 VMS 长期以来一直被认为只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。最先进的新证据 VMS 的生理测量表明 VMS 可能与较差的认知功能和 大脑结构和功能的不良变化。平行研究将 VMS 与不良 CVD 风险联系起来 因素概况和更大的亚临床 CVD。在拟议的研究中，我们将测试是否更频繁或 持续的 VMS 与不良的大脑结构和功能结果以及较差的认知能力有关 功能。我们将测试 CVD 危险因素和亚临床 CVD 在这些关联中的作用，同时另外 考虑睡眠、负面情绪和雌二醇浓度的作用。最后，我们将测试 APOE 状态为 VMS 认知和大脑关系的调节者。我们将在 230 名女性样本中解答这些问题 招募自一组没有心血管疾病和痴呆症的中年女性，她们接受了详细的治疗 他们的 VMS 的生理特征以及荷尔蒙、睡眠和 CVD 风险状况。我们将 邀请队列返回重复 VMS 的动态生理测量；超声测量 亚临床CVD（颈动脉内膜中层厚度）；睡眠活动记录评估；和 CVD 的血液标志物 危险因素和雌二醇。我们还将扩展电池以包括认知测试； APOE 基因分型；和 功能和结构脑成像。这项研究的结果有可能将 VMS 识别为女性 可以识别有认知能力下降风险的中年女性的特定标记。这项工作最终可能有助于 早期干预措施旨在改善女性认知、增强大脑储备并降低 AD 风险。