Physical activity predictors of cognitive and brain health in the risk for Alzheimer's disease

认知和大脑健康的体力活动预测阿尔茨海默氏病的风险

基本信息

批准号：
10228383
负责人：
GENE E ALEXANDER
金额：
$ 76.75万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228383
关键词：
Accelerometer Address Aerobic Aerobic Exercise Age Aging Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease risk Base of the Brain Behavior Behavior Therapy Behavioral Blood Blood Vessels Brain Brain region Brain scan Brain-Derived Neurotrophic Factor Cognition Cognitive Communities Data Data Analytics Disease Effectiveness Elderly Exercise Family Foundations Fractals Genetic Hippocampus (Brain)Impaired cognition Individual Differences Intervention Lesion Life Style Link MRI Scans Measures Mediating Mediation Memory Methods Neurodegenerative Disorders Outcome Paired-Associate Learning Participant Pathway interactions Patient Self-Report Pattern Peripheral Physical activity Physiological Plasma Predisposition Prevalence Prevention therapy Public Health Recording of previous events Regulation Research Rest Risk Role Structure Subgroup Testing Therapeutic Intervention Update VO2max Variant Vascular Endothelium Work activity marker aging brain base behavior measurement brain health cardiorespiratory fitness cerebrovascular cognitive ability cognitive function cognitive process cohort endothelial stem cell exercise intervention inter-individual variation moderate-to-vigorous physical activity multimodality neurogenesis neuroimaging novel peripheral blood pre-clinical prevent relating to nervous system resilience response sedentary lifestyle white matter

项目摘要

Abstract Alzheimer’s disease is a progressive neurodegenerative disorder leading to profound losses in brain and cognitive abilities. With a projected prevalence of over 14 million by 2050, Alzheimer’s disease represents a growing public health crisis. Research on disease modifying interventions that can slow or prevent Alzheimer’s disease is critically needed, including on modifiable lifestyle behaviors that can act through peripheral systemic mechanisms to enhance resilience against cognitive decline in those with increased risk for Alzheimer’s disease. Recent work has linked aerobic physical activity (PA) to enhanced cerebrovascular function and hippocampal neurogenesis, suggesting pathways to support brain regions vulnerable to Alzheimer’s disease. However, results relating PA and Alzheimer’s disease risk have been mixed, potentially due to differences in how PA is assessed, ranging from self-report to behavioral to physiological measures, as well as inter-individual variation in peripheral systemic physiological responses to PA. There is an urgent need to identify how different PA measures influence cognitive decline in brain aging and preclinical Alzheimer’s risk, and to determine which PA markers best predict differences in susceptibility to Alzheimer’s disease, so brain-based mechanisms can be effectively targeted for PA-based interventions. We plan to evaluate 270 community-dwelling older adults, ages 70 to 84, to obtain baseline physiological measures of cardiorespiratory fitness, behavioral measures of PA from wearable accelerometry, and peripheral blood neurogenic (brain-derived neurotrophic factor) and vascular (endothelial progenitor cells) markers assessed before and after an exercise challenge, together with subjective ratings of recent and lifelong PA. Participants will be evaluated at 18-month intervals to assess trajectories of decline in hippocampal-related memory and frontal-related executive cognitive functions, as well as magnetic resonance imaging scans of brain structure, resting functional connectivity, and white matter integrity and hyperintensity lesion load. The cohort will include those with and without increased preclinical Alzheimer’s disease risk, defined by first-degree Alzheimer’s disease family history and subjective memory concerns. This proposal will address the following specific aims: to investigate how behavioral markers of PA predict longitudinal change in 1) cognitive function and 2) brain structure and functional connectivity in relation to preclinical risk for Alzheimer’s disease; to evaluate how peripheral systemic physiological markers of PA predict longitudinal change in cognition and brain structure and functional connectivity in relation to Alzheimer’s disease risk; and to determine how the peripheral systemic response to aerobic exercise mediates the relation between PA and longitudinal changes in brain and cognition in those with and without increased Alzheimer’s disease risk. By evaluating a novel, comprehensive set of PA markers and testing their effects on trajectories of cognition and brain in relation to Alzheimer’s disease risk, this proposal provides a unique opportunity to obtain key data needed to help advance efforts in developing effective exercise-based interventions for Alzheimer’s disease prevention.

抽象的阿尔茨海默氏病是一种进行性神经退行性疾病，导致大脑和认知能力。到2050年，阿尔茨海默氏病预计的患病率超过1400万，代表着越来越多的公共卫生危机。疾病修改干预措施的研究可以减慢或预防阿尔茨海默氏症迫切需要疾病，包括可以通过周围系统性起作用的可修改生活方式行为在阿尔茨海默氏病风险增加的患者中，对认知能力下降的弹性的机制。最近的工作将有氧运动（PA）与增强的脑血管功能和海马联系起来神经发生，提出了支持大脑区域容易受到阿尔茨海默氏病的途径。但是，结果有关PA和阿尔茨海默氏病风险的关系已经混合在一起，这可能是由于评估PA的差异，从自我报告到行为到身体测量，以及外周的个体差异对PA的系统性物理反应。迫切需要确定不同的PA措施如何影响大脑衰老和阿尔茨海默氏临床前风险的认知能力下降，并确定哪些PA标记最能预测对阿尔茨海默氏病的敏感性差异，因此可以有效地将基于大脑的机制定位于基于PA的干预措施。我们计划评估70至84岁的270名社区居民老年人心肺健康的基线物理测量，可穿戴的PA行为测量加速度法和外周血神经源（脑源性神经营养因子）和血管（内皮祖细胞）在运动挑战之前和之后评估的标记，以及近期和终身PA。参与者将以18个月的间隔进行评估，以评估海马相关的记忆和与前部的执行认知功能以及磁共振成像扫描大脑结构，静止功能连通性以及白质完整性和高强度病变负荷。该队列将包括有或没有增加临床前阿尔茨海默氏病风险的人群。一级阿尔茨海默氏病的家族史和主观记忆的问题。该建议将解决以下具体目的：研究PA的行为标记如何预测1中的纵向变化）认知功能和2）与阿尔茨海默氏临床前风险有关的大脑结构和功能连通性疾病;评估PA的外围系统生理标志物如何预测认知的纵向变化与阿尔茨海默氏病风险有关的大脑结构和功能连通性；并确定如何对有氧运动的外围系统反应介导了PA与纵向变化之间的关系患有和没有阿尔茨海默氏病风险的人的大脑和认知。通过评估小说，全面的PA标记集并测试其对认知和大脑轨迹的影响阿尔茨海默氏病风险，该提案提供了一个独特的机会，以获取帮助促进的关键数据为预防阿尔茨海默氏病开发有效的基于运动的干预措施的努力。