Neuroanatomical Substrates of Aging & Cognitive Decline

衰老的神经解剖学基础

• 批准号: 7049840
• 负责人: GENE E ALEXANDER
• 金额: $ 40.74万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049840
• 关键词: aerobic exercise; aging; apolipoprotein E; behavioral /social science research tag; brain mapping; clinical research; cognition disorders; diffusion magnetic resonance imaging; genetic screening; genetic susceptibility; gray matter; human genetic material tag; human middle age (35-64); human old age (65+); human subject; longitudinal human study; magnetic resonance imaging; nervous system disorder epidemiology; neuroimaging; neuropathology; neuropsychological tests; physical fitness; psychological aspect of aging; white matter

DESCRIPTION (provided by applicant): The goal of the current study is to investigate how individual differences in health status and genetic risk for cognitive impairment affect the regional distribution and severity of brain changes associated with aging and age-related cognitive decline. Previous studies have shown that the frontal cortex is preferentially affected in aging and is important for cognitive abilities that often decline with age, including working memory, attention, and executive functions. Several health and genetic risk factors have been specifically associated with declines in cognition and brain abnormalities in regions of the temporal, parietal, cingulate, and frontal cortices and white matter in otherwise neurologically healthy elderly. Among these factors include differences in blood pressure, aerobic fitness, and the presence of the apolipoprotein E (APOE) s4 allele, a common susceptibility gene for Alzheimer's disease. Health and genetic risks factors may interact with the effects of aging to account for the heterogeneity of cognitive decline and atrophic brain regions commonly observed among active elderly, living in the community. We plan to study 222 community dwelling, neurologically healthy elderly with baseline tests of ambulatory blood pressure and aerobic fitness, baseline and two year follow-up structural and diffusion tensor magnetic resonance imaging (MRI) scans, APOE genotyping, and baseline and two year follow up assessments of cognitive function using a battery of standardized neuropsychological tests. We will test hypotheses using regional univariate and multivariate network analysis methods with voxel-based MRI morphometry to identify the baseline and two year longitudinal changes in gray and white matter associated with aging; to determine how age interacts with three potentially modifying factors: a) blood pressure, b) aerobic fitness, and c) APOE genotype to alter the regional distribution and severity of baseline and two year longitudinal gray and white matter changes in aging; and to evaluate how specific brain regions identified by the interactive effects of aging with health status and genetic risk for cognitive impairment are associated with baseline and two year declines in cognition. It is expected that results from this study will significantly enhance our understanding of the brain changes associated with aging and related cognitive decline, help to identify those at greatest risk for age- related cognitive dysfunction, and provide a foundation to develop and test focused strategies to delay or prevent the brain changes that lead to cognitive decline in aging.

描述（由申请人提供）：当前研究的目的是研究健康状况和认知障碍的遗传风险的个体差异如何影响与衰老和与年龄相关的认知能力下降相关的大脑变化的区域分布和严重程度。先前的研究表明，额叶皮层在衰老中优先影响，并且对于经常随着年龄的增长（包括工作记忆，注意力和执行功能）而下降的认知能力很重要。几种健康和遗传危险因素与颞，顶，山顶，扣带和额叶皮质的认知和脑异常下降特别相关，而神经学健康的老年人则是白质。在这些因素中，包括血压的差异，有氧健身和载脂蛋白E（APOE）S4等位基因的存在，这是阿尔茨海默氏病的常见易感基因。健康和遗传风险因素可能与衰老的影响相互作用，以说明认知能力下降的异质性和贫血的大脑区域，通常在活跃的老年人中观察到生活在社区中。我们计划研究222个社区居住，神经健康的老年人，对卧床血压和有氧运动的基线测试，基线和两年的随访结构和扩散量张量磁共振成像（MRI）扫描，APOE基因分型，基线以及基线以及使用标准的Neuropsysics bowderative neuropsysiss测试的认知功能进行了两年的随访评估。我们将使用基于体素的MRI形态测定法的区域单变量和多变量网络分析方法检验假设，以识别与衰老相关的灰色和白质的基线和两年的纵向变化；确定年龄如何与三个潜在的修改因素相互作用：a）血压，b）有氧健身和c）apoE基因型，以改变基线的区域分布和严重程度以及两年的衰老纵向变化；并评估特定的大脑区域如何通过健康状况和认知障碍的遗传风险的衰老效果鉴定出来与基线和两年的认知有关。可以预期，这项研究的结果将显着增强我们对与衰老和相关认知能力下降相关的大脑变化的理解，有助于确定那些与年龄相关的认知功能障碍最大风险的人，并为发展和测试集中策略延迟或防止大脑变化导致衰老的认知能力下降。