Energy Reserves, Physical Activity, and Alzheimer's Disease in the Baltimore Longitudinal Study of Aging

巴尔的摩衰老纵向研究中的能量储备、体力活动和阿尔茨海默病

• 批准号: 9922189
• 负责人: JENNIFER ANN SCHRACK
• 金额: $ 60.1万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922189
• 关键词: Accelerometer; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Ankle; Apolipoprotein E; Atrophic; Baltimore; Blood Vessels; Brain; Brain Pathology; Cerebrovascular Circulation; Clinical; Clinical Markers; Clinical Research; Cognition; Cognitive; Cohort Studies; Complex; Data; Data Collection; Dementia; Development; Diagnosis; Disease; Disease Progression; Early Diagnosis; Elderly; Energy Metabolism; Enrollment; Etiology; Exhibits; Family; Future; Gait; Gait abnormality; Gait speed; Genotype; Health; Impaired cognition; Indirect Calorimetry; Individual; Inflammation; Inflammatory; Intervention; Laboratories; Lead; Link; Longitudinal Studies; Magnetic Resonance Imaging; Market Research; Measures; Mediating; Mediator of activation protein; Memory; Monitor; Motor; Movement Disorders; Neuronal Injury; Outcome; Pathologic; Pathology; Pattern; Persons; Phenotype; Physical Function; Physical activity; Physiologic pulse; Physiological; Pittsburgh Compound-B; Positron-Emission Tomography; Predictive Value; Regulation; Research; Risk; Role; Sensitivity and Specificity; Societies; Structure; Time; Translational Research; Vascular Diseases; Walking; Woman; Work; abeta deposition; adjudicate; adjudication; apolipoprotein E-4; base; burden of illness; cerebral atrophy; cognitive function; cognitive performance; cost; disorder risk; early screening; executive function; fitness; follow-up; high risk; indexing; men; mild cognitive impairment; pre-clinical; preservation; prevent; processing speed; research study; sex; wearable device; β-amyloid burden

PROJECT SUMMARY Alzheimer’s disease (AD) is the most common cause of dementia. Underlying pathological and physiological changes related to the onset and progression of AD are believed to emerge several years prior to clinical manifestations. Gait abnormalities and motor slowing typically precede the diagnosis of AD by a decade or more, presenting the exciting possibility that changes in gait may act as early noninvasive biomarkers for AD. Previous work by our group has identified key markers of impending and/or accelerated gait speed decline based on physiological measures of the energy cost of slow walking, peak energy capacity, and quantities and patterns of objectively measured free-living physical activity (PA), making them potential preclinical markers of early AD pathology. We propose to use 8 years of existing longitudinal data, and ongoing/new data collection in nearly 1,000 older adults in the Baltimore Longitudinal Study of Aging (BLSA), to examine the roles of altered energy reserves, and reduced and fragmented daily PA as precursors to clinical markers of Alzheimer’s disease and neuronal injury, which include Aβ deposition using [11C]-Pittsburgh compound B positron emission tomography, brain atrophy using structural magnetic resonance imaging (MRI), and cognitive performance. We will also explore potential vascular mechanisms linking energy reserves and PA to these outcomes, including cerebral blood flow, ankle brachial index, and pulse wave velocity, as well as the role of mediating or modifying factors such as inflammation and the apolipoprotein E genotype. The BLSA is a continuously enrolled cohort study of aging that already contains repeated measures of cognition and adjudication of cognitive status, in which a subset completes repeated MRI and PiB PET scans. Importantly, our preliminary cross-sectional data from the BLSA indicate strong associations among energy reserves, cognitive performance, b-amyloid burden, and diurnal patterns of daily PA. We propose to investigate the longitudinal associations among these variables to identify physiological thresholds of poor energy reserve and reduced and fragmented patterns of diurnal PA as early precursors to the onset and progression of AD pathology. A better understanding of the association between energy reserves/PA, subclinical AD pathology, and cognitive performance may elucidate a physiological threshold of diminished energy reserve that is associated with increased risk of poor cognitive outcomes over time, and increase our understanding of the complex association between declines in physical and cognitive functioning with age. Moreover, uncovering patterns of daily free-living PA most commonly associated with this threshold will help define a phenotype of reduced and/or fragmented PA that signifies impending emergence and progression of AD. Given the proliferation of wearable devices to monitor PA in the consumer and research markets, identifying changes in PA consistent with the development of AD pathology could provide evidence for future wide-scale screening for early detection of persons at high risk of AD.

项目摘要 阿尔茨海默氏病（AD）是痴呆症的最常见原因。基础病理和生理 据信与AD的发作和进展有关的变化在临床前几年出现 表现。步态异常和运动速度通常是在AD诊断前十年之前或 更重要的是，呈现出GET变化的令人兴奋的可能性可能是AD的早期非侵入性生物标志物。 我们小组的先前工作已经确定了即将和/或加速速度下降的关键标记 基于慢速步行，峰值能量和数量的能源成本的物理衡量 客观测量的自由活动（PA）的模式，使它们成为潜在的临床前标记 早期广告病理学。我们建议使用8年的现有纵向数据，以及正在进行的/新数据收集 在巴尔的摩纵向研究（BLSA）的近1,000名老年人中， 改变能源储量，减少和分散的每日PA作为阿尔茨海默氏症临床标志物的前体 疾病和神经元损伤，其中包括使用[11C] -Pittsburgh化合物B polaron发射的Aβ沉积 层析成像，使用结构磁共振成像（MRI）和认知性能。 还将探索将能源储量和PA与这些结果联系起来的潜在血管机制，包括 脑血流，踝臂指数和脉搏波速度以及介导或修饰的作用 炎症和载脂蛋白E基因型等因素。 BLSA是连续入学的队列 对已经包含认知和调整认知状况调整的衰老的研究， 子集完成了重复MRI和PIB PET扫描。重要的是，我们的初步横截面数据 来自BLSA，表明能量储量之间的牢固关联，认知性能，B-淀粉样蛋白Burnen， 和日常PA的昼夜模式。我们建议研究其中的纵向关联 变量以识别能源储备不良的物理阈值以及减少和分散的模式 Diurnal PA是AD病理发作和进展的早期前体。更好地理解 能源储备/PA，亚临床AD病理学和认知表现之间的关联可能会阐明 能源储备降低的物理阈值与认知差的风险增加有关 随着时间的推移结果，并提高了我们对物理下降之间复杂关联的理解 和认知功能随着年龄的增长。此外，最常见的是每天自由生活PA的模式 与此阈值相关的将有助于定义减少和/或碎片的PA的表型 即将出现的AD出现和进展。考虑到可穿戴设备的扩散以监视PA 消费者和研究市场，确定PA的变化与AD病理的发展一致 可以为未来的广泛筛查提供证据，以及早发现AD高风险的人。