The Effect of Physical Activity on Cognition Relative to APOE Genotype

体力活动对 APOE 基因型认知的影响

• 批准号: 8516937
• 负责人: JENNIFER L ETNIER
• 金额: $ 16.95万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516937
• 关键词: Adherence; Adverse effects; Alzheimer' s Disease; Alzheimer' s disease risk; Animals; Apolipoproteins; Behavioral; Brain-Derived Neurotrophic Factor; Cognition; Cognitive; Data; Development; Dose; Elderly; Family history of; Future; Gender; Genetic Risk; Genotype; Gray unit of radiation dose; Human; Impaired cognition; Individual; Intervention; Length; Link; Literature; Maintenance; Measures; Mediating; Memory; Memory impairment; Modeling; Motivation; Participant; Performance; Peripheral; Persons; Physical activity; Prevalence; Prevention strategy; Preventive; Process; Prospective Studies; Public Health; Randomized Controlled Trials; Recruitment Activity; Relative (related person); Research; Research Design; Resources; Risk; Role; Sampling; Simulate; Statistical Methods; Statistical Models; Susceptibility Gene; Techniques; Testing; Time; Work; apolipoprotein E-4; base; cost effective; design; effective intervention; executive function; experience; interest; middle age; mild cognitive impairment; performance tests; pre-clinical; programs; prospective; research study; response; simulation

DESCRIPTION (provided by applicant): By 2030, the global prevalence of Alzheimer's disease (AD) is predicted to reach 65.7 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is important to identify preventive strategies that can reduce the risk of or delay the onset of AD [1]. Physical activity (PA) has potential as a preventative strategy. Our research [2, 3] and that of others [4, 5] shows that older adults who participate in PA experience larger gains in cognitive performance than do controls. Prospective studies also show that PA is associated with a lower risk of AD [6-9] and that the relationship between baseline PA and subsequent cognitive performance is moderated by a susceptibility gene for AD (apolipoprotein, APOE) [10-13]. However, the potential moderating role of APOE genotype on the effects of PA on cognitive performance has not been tested experimentally in humans; thus we do not know who receives the greatest cognitive benefits from PA. Additionally, we do not understand the mechanisms which explain how PA benefits cognitive performance. These gaps in the literature are the motivation behind our long range plan of research designed to further our understanding of the potential role of PA in the mitigation of cognitive decline and in the delay of AD. These gaps are also the impetus for this specific study in which we: 1) establish the feasibility of an 8-month PA intervention with persons with a family history of AD and use statistical modeling to inform the design of a future randomized control trial (RCT); 2) assess change in cognitive performance across the PA intervention and determine whether this change differs as a function of APOE genotype; 3) determine whether change in peripheral brain-derived neurotrophic factor, pBDNF (which is a plausible mechanism of the effects and has been linked to AD) predicts change in cognitive performance across the PA intervention; and 4) examine the differential effects of APOE genotype on the effects of PA on various cognitive domains. We will ascertain APOE genotype in 100 older cognitively normal individuals to identify APOE e4 carriers (n=30) and gender-matched non-carriers (n=30) to participate in an 8-month PA program. We will assess cognitive performance at baseline and will assess cognitive performance and pBDNF at the pre-test, mid-test, and post-test. This initial study will provide foundational evidence and will guide the development of a RCT further testing the moderating role of APOE genotype and the mediating role of pBDNF on the effects of PA on cognitive performance. The identification of effective interventions for the maintenance of cognitive performance in older adults at risk for AD has important public health implications because few preventive strategies for AD have been identified and because a therapy that delays the development of AD by 5 years could reduce the risk of AD by 50%. PA has promise in this regard and is particularly attractive because it is cost-effective and has relatively few negative side-effects. Further, if PA is beneficial for persons with a genetic risk for AD, this cold be particularly important because these individuals show signs of preclinical AD in middle-age [14, 15].

描述（由申请人提供）：到2030年，全球阿尔茨海默病（AD）患病率预计将达到6570万。尽管全世界都在努力研究，但阿尔茨海默病的治疗方法尚未确定。因此，重要的是确定可以减少这种情况的预防战略

项目成果

Innovative Research Design Exploring the Effects of Physical Activity and Genetics on Cognitive Performance in Community-Based Older Adults.

创新研究设计探索体育活动和遗传学对社区老年人认知表现的影响。

• DOI: 10.1123/japa.2014-0221
• 发表时间: 2015
• 期刊: Journal of aging and physical activity
• 影响因子: 1.5
• 作者: Etnier,JenniferL;Labban,JeffreyD;Karper,WilliamB;Wideman,Laurie;Piepmeier,AaronT;Shih,Chia-Hao;Castellano,Michael;Williams,LaurenM;Park,Se-Yun;Henrich,VincentC;Dudley,WilliamN;Rulison,KelliL
• 通讯作者: Rulison,KelliL