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.

阿尔茨海默氏病（AD）是美国痴呆症的主要原因。女人尤其是 受广告影响。与男性相比，女性的AD患病率更高，AD的风险更高 载脂蛋白（APOE）-ε4等位基因，并且在诊断性认知后的认知下降速度更快 损害或广告。 AD的神经病理学标志从中年开始奠定，并不断增加 证据支持有必要更好地了解自然早期认知变化的中年风险因素 广告的历史。但是，很少有研究检查了特定性别的中年危险因素。更年期是 关键的中年过渡会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，主观记忆投诉的小但显着下降， 标准化记忆测试的性能，大脑通过更年期的妇女过渡。 加速动脉粥样硬化的积累和关键心血管疾病（CVD）危险因素的担忧 在此期间也很常见。这些大脑和心血管变化并非仅由于衰老。 此外，超过70％的中年妇女报告了更年期血管舒缩症状（VMS）；对于三分之一的女人 长期以来，VM一直被认为是生活质量问题， 但是最近的发现使这一假设提出了质疑。新兴证据 VM的生理测量指标表明，VM可能与较差的认知功能和 大脑结构和功能的不利变化。一条平行的研究线将VM链接到不利的CVD风险 因子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VM与不良结构和功能性脑结果有关，认知较差 功能。我们将测试CVD风险因素和亚临床CVD在这些关联中的作用，同时 考虑睡眠的作用，负面情绪和雌二醇的浓度。最后，我们将测试APOE状态为 VMS认知和大脑关系的主持人。我们将在230名女性样本中解决这些问题 从已有详细的CVD和痴呆症的中年妇女组成的既定妇女队列中招募 其VM以及其马，睡眠和CVD风险概况的生理表征。我们将 邀请队列重复对VM的门诊生理测量；超声测量 亚临床CVD（颈动脉内膜培养基厚度）；睡眠评估；和CVD的血标记 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 功能性和结构性脑成像。这项研究的发现有可能将VM识别为女性 可以识别有认知能力下降风险的中年妇女的特定标记。这项工作最终可能有助于 早期干预措施改善认知，增强大脑储备并降低女性广告的风险。