Inactivity, sedentary behavior, and the risk for Alzheimer’s disease in middle aged to older adults

中老年人缺乏活动、久坐行为和患阿尔茨海默病的风险

基本信息

批准号：
10595061
负责人：
GENE E ALEXANDER
金额：
$ 66.57万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10595061
关键词：
Accelerometer Address Adult Aging Algorithms Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease risk Atherosclerosis Atrophic Attention Attenuated Behavior Behavior Therapy Brain Cognition Cognitive Cognitive deficits Communities Computerized Medical Record Computers Data Data Set Dementia Dose Elderly Exercise Foundations Framingham Heart Study Genetic Health Hippocampus Impaired cognition Incidence Individual Intervention Length Life Style Measurement Measures Memory Methods Modeling Morbidity - disease rate Multi-Ethnic Study of Atherosclerosis Neurodegenerative Disorders Outcome Participant Pathway Analysis Patient Self-Report Pattern Physical activity Physiological Prevention therapy Prospective cohort Psyche structure Recommendation Risk Sampling Scanning Structure Testing Therapeutic Intervention Time White Matter Hyperintensity Work aging brain behavior prediction biobank brain based brain health cerebral atrophy cognitive function cognitive testing cohort effective intervention effective therapy electronic data executive function follow-up human old age (65+)improved lifestyle intervention machine learning algorithm middle age mortality neuroimaging novel prospective response secondary analysis sedentary sedentary lifestyle tv watching

项目摘要

Abstract Alzheimer’s disease is a devastating progressive neurodegenerative disease that leads to a profound loss of brain and cognitive functions. There is an urgent need to identify factors that can decrease risk, including modifiable lifestyle behaviors. Exercise and physical activity (PA) have shown promise in reducing rates of cognitive decline, brain structural atrophy, and risk of developing Alzheimer’s disease and other related dementias. However, despite decades of work, and recommendations to improve exercise participation, levels of PA and engagement in purposeful exercise have not increased greatly. In contrast to PA, the effect of sedentary behavior (SB) or time spent sitting on Alzheimer’s disease risk has received less attention. SB may have independent physiological effects on health which may not be fully ameliorated by engaging in PA, and there is growing evidence that SB may have detrimental effects on cognition and brain structure. Understanding the effects of SB on Alzheimer’s disease risk may provide a key target for behavioral modification since reducing time spent sitting may be easier to implement compared to increasing exercise levels in older adults. In this proposal, we will determine whether time spent in SB is associated with brain health and the risk of developing Alzheimer’s disease and all-cause dementia. Here, we focus on the effects of SB on cognition, brain structure, and Alzheimer’s disease incidence in the largest prospective cohort analyzed to date, the UK Biobank. We will analyze associations between markers of SB including self-report and objective measures from wearable accelerometers, and cognition, brain health, and incident Alzheimer’s disease and all-cause dementia. This unique dataset will allow us to determine the best SB predictors of brain aging outcomes, including Alzheimer’s disease incidence so that interventions can focus on reducing the most harmful aspects of SB in older adults. Using this dataset along with three replication datasets, we will test our overarching hypothesis that high levels of SB are associated with increased cognitive decline, poorer brain health, and increased Alzheimer’s disease risk that is not fully mitigated by complementary engagement in PA. To test this hypothesis, this proposal will address the following specific aims: 1) to determine how SB is associated with incident Alzheimer’s disease and all-cause dementia, 2) to evaluate the cross-sectional and prospective relationships between SB and aspects of cognition and brain structure associated with Alzheimer’s disease risk, and 3) to investigate how displacing SB with time spent in different PA levels modifies the association between SB and Alzheimer’s disease risk. By evaluating a novel, comprehensive set of SB markers and testing their associations with cognition, brain structure, and Alzheimer’s disease risk, this proposal provides a unique opportunity to obtain key data needed to help advance efforts in developing effective interventions for Alzheimer’s disease prevention.

抽象的阿尔茨海默氏病是一种毁灭性的进行性神经退行性疾病，导致了深远的丧失大脑和认知功能。迫切需要确定可以降低风险的因素，包括可修改的生活方式行为。运动和体育锻炼（PA）已显示出降低率的承诺认知能力下降，大脑结构性萎缩以及患阿尔茨海默氏病及其他相关的风险痴呆症。但是，尽管工作数十年，并提出了改善运动参与的建议 PA和参与有目的的运动并没有大大增加。与PA相反，久坐行为（SB）或坐在阿尔茨海默氏病风险上花费的时间受到较少的关注。 SB可能对健康产生独立的身体影响，这可能无法通过参与PA来完全改善，并且越来越多的证据表明，SB可能对认知和大脑结构有不利影响。理解 SB对阿尔茨海默氏病风险的影响可能为行为修改提供关键目标，因为与增加老年人的运动水平相比，花费的时间可能更容易实施。在此提案中，我们将确定在SB上花费的时间是否与大脑健康有关发展阿尔茨海默氏病和全因痴呆症。在这里，我们专注于SB对认知，大脑的影响迄今为止，在英国生物银行分析的最大的前瞻性队列中，结构和阿尔茨海默氏病。我们将分析SB标记之间的关联，包括自我报告和可穿戴的客观措施加速度计，认知，大脑健康以及阿尔茨海默氏病和全因痴呆症的事件。这独特的数据集将使我们能够确定大脑衰老结果的最佳SB预测指标，包括阿尔茨海默氏症疾病事件，因此干预措施可以集中于减少老年人中SB最有害的方面。使用此数据集以及三个复制数据集，我们将测试高级的总体假设 SB的认知能力下降，大脑健康较差和阿尔茨海默氏病的增加有关在PA中互补的参与并不能完全缓解风险。为了检验这一假设，该提议将解决以下具体目的：1）确定SB与Alzheimer疾病的发生如何相关全因痴呆症，2）评估SB与方面之间的横截面和前瞻性关系与阿尔茨海默氏病风险相关的认知和大脑结构，以及3）研究如何取代SB 随着时间的流逝，PA级别花费的时间改变了SB与阿尔茨海默氏病风险之间的关联。经过评估一套新颖的，全面的SB标记，并测试其与认知的关联结构和阿尔茨海默氏病风险，该提案提供了一个独特的机会，以获取所需的关键数据帮助促进为预防阿尔茨海默氏病的有效干预措施而努力。