EFFECTS OF VULNERABILITY AND RESILIENCY ON BRAIN HEALTH DURING THE MID-TO-LATE-LIFE TRANSITION

中晚年过渡期间脆弱性和弹性对大脑健康的影响

• 批准号: 10673904
• 负责人: Helen Lavretsky
• 金额: $ 23.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673904
• 关键词: Acceleration; Adult; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid beta-42; Anisotropy; Behavior; Biological Markers; Blood Pressure; Blood Vessels; Body mass index; Brain; Cerebrovascular Circulation; Cholesterol; Cognition; Cognitive; Cognitive aging; Cohort Studies; Cross-Sectional Studies; Data; Dementia; Development; Diagnosis; Diet; Diffusion Magnetic Resonance Imaging; Disease; Elderly; Encephalitis; Episodic memory; Exercise; Functional Magnetic Resonance Imaging; Genetic; Glucose Intolerance; Glycosylated hemoglobin A; Habits; Health; Hippocampus; Human; Hypertension; Image; Impaired cognition; Incidence; Individual; Inflammation; Insulin Resistance; Intervention; Investments; Life Expectancy; Life Style; Light; Link; Longevity; Magnetic Resonance Spectroscopy; Measures; Metabolic syndrome; Nerve Degeneration; Obesity; Outcome; Pathology; Pathway interactions; Peptide Initiation Factors; Perimenopause; Persons; Plasma; Population; Populations at Risk; Reporting; Research; Resistance; Rest; Risk; Risk Factors; Risk Marker; Risk Reduction; Role; Secondary to; Sleep; Sleep disturbances; Stress; Structural Models; Structure; Thick; Time; Translating; Vascular Dementia; Visit; Width; Woman; actigraphy; allostatic load; apolipoprotein E-4; arterial spin labeling; brain health; cingulate cortex; cognitive change; connectome; dementia risk; demographics; disorder risk; episodic memory impairment; follow-up; genetic risk factor; healthy lifestyle; lifestyle factors; longitudinal analysis; middle age; modifiable lifestyle factors; modifiable risk; neural; neurofilament; neuroinflammation; normal aging; novel therapeutics; polygenic risk score; poor sleep; prevent; processing speed; protective factors; resilience; resilience factor; tau-1; white matter

ABSTRACT FOR PROJECT 2 An effective disease-modifying treatment for Alzheimer’s dementia (AD) or AD related dementias (ADRD) is not available, underscoring the pressing need to identify brain health protective factors that reduce risk for cognitive decline, AD, and ADRD. A critical time that influences the impact of modifiable risk factors is the transition from midlife to late life (50 to 80 years). Research also has demonstrated the role of inflammation in neurodegeneration, and disrupting brain inflammation may reduce dementia risk. It is thus critical to determine relative contributions of these vulnerability/resiliency factors to cognitive health and inflection points when specific risk reduction interventions may be most effective. Findings from the Human Connectome Project (HCP) indicate a strong positive-negative mode of population covariation that links brain connectivity, demographics and behavior. This project offers an unprecedented opportunity to examine such factors longitudinally during a critical inflection point when lifestyle factors begin to initiate a downward brain health trajectory. To elucidate these relationships, this project will address the following specific aims focused on the mid to-late-life transition: (1) Determine the effects of modifiable vulnerability and resilience factors in the mid-to late-life transition (exercise, sleep, diet, stress (with P1); measures of health (Body Mass Index (BMI), blood pressure (BP), insulin resistance (HbA1c), cholesterol), on structural connectivity (measured with Diffusion Tensor Imaging (DTI); functional connectivity(resting state functional connectivity (rsFC); task fMRI) and cognition (2) Determine the unique contributions of AD risk factors and markers vs. modifiable lifestyle factors and health markers on the trajectory of brain and cognitive change across the mid-late life transition using cross-sectional and longitudinal analysis; (3) Identify the most likely structural model that connects brain and cognitive outcomes in the AABC longitudinal data with AD biomarkers, baseline cognitive, age, AD risk and lifestyle. 4) Integration with other projects and the Center as a whole to examine lifetime, non-linear trajectories of brain and cognitive aging, resistance to AD, risk, and resilience. To accomplish these aims, we will perform longitudinal follow-up of 764 subjects in the mid- to late-life transition (ages 50 to 80) and include measures assessing lifestyle and resilience (e.g., actigraphy, sleep, diet) and coordinate with the cores and other projects to include other measures and variables relevant to these aims. With the accumulation of evidence that mitigation of AD risk can delay or prevent the disease, there is a need to identify, inform and intervene in people at greatest dementia risk. When started early, even relatively modest risk reduction may translate to significant declines in disease incidence. This project offers the opportunity to leverage a well-studied cohort of normal aging middle-aged and older adults, many with a decade of longitudinal data.

项目2摘要 阿尔茨海默氏症（AD）或AD相关痴呆症（ADRD）的有效改良疾病改良治疗 不可用，强调识别大脑健康保护因素的紧迫需求，以降低风险 认知能力下降，AD和ADRD。影响可修改风险因素影响影响的关键时间是 从中年过渡到后期生活（50至80年）。研究还证明了炎症在 神经变性和破坏大脑感染可能会降低痴呆症风险。因此，确定 这些脆弱性/弹性因素对认知健康和拐点的相对贡献 具体的降低风险干预措施可能最有效。人类Connectome项目（HCP）的发现 指示有强大的积极阴性模式的人口协方差，该模式将大脑连通性，人口统计联系起来 和行为。该项目提供了前所未有的机会，可以在 当生活方式因素开始启动脑部健康轨迹时，关键的拐点。阐明 这些关系，该项目将解决以下特定目标，该目标的重点是中期生活过渡： （1）确定可修改的脆弱性和弹性因素在中期过渡中的影响 （运动，睡眠，饮食，压力（带P1）；健康度量（体重指数（BMI），血压（BP），胰岛素 抗性（HBA1C），胆固醇），在结构连通性上（通过扩散张量成像（DTI）测量； 功能连接性（静止状态功能连接（RSFC）；任务fMRI）和认知（2）确定 广告风险因素和标志物与可修改的生活方式因素和健康标记的独特贡献 使用横截面和纵向的大脑和认知变化的轨迹和认知变化 分析; （3）确定将大脑和认知结果连接到AABC中的最可能的结构模型 具有广告生物标志物，基线认知，年龄，AD风险和生活方式的纵向数据。 4）与其他集成 项目和整个中心，以检查寿命，大脑和认知衰老的非线性轨迹， 抵抗AD，风险和弹性。为了实现这些目标，我们将执行764的纵向随访 中期到后期过渡的受试者（50至80岁），包括评估生活方式和韧性的措施 （例如，行动学，睡眠，饮食）并与核心和其他项目进行协调，以包括其他措施和 变量与这些目标有关。有很多证据表明缓解AD风险可能会延迟或阻止 这种疾病需要识别，告知和干预最大痴呆症风险的人。何时开始 早期，即使是相对适度的降低风险也可能转化为疾病事件的大幅下降。这个项目 提供机会利用一个经过精心研究的正常老龄化中年和老年人的队列，许多人 十年的纵向数据。