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。女性尤其如此