Neuroanatomical Substrates of Aging & Cognitive Decline

描述（由申请人提供）：本研究的目的是调查健康状况和认知障碍遗传风险的个体差异如何影响与衰老和年龄相关的认知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，额叶皮层在衰老过程中优先受到影响，并且对认知能力很重要，这些认知能力通常会随着年龄的增长而下降，包括工作记忆，注意力和执行功能。一些健康和遗传风险因素与认知能力下降和颞叶、顶叶、扣带回、额叶皮质和白色物质区域的大脑异常特别相关。这些因素包括血压、有氧健身和载脂蛋白E（APOE）s4等位基因（阿尔茨海默病的常见易感基因）的差异。健康和遗传风险因素可能与衰老的影响相互作用，以解释生活在社区中的活跃老年人中常见的认知能力下降和萎缩脑区的异质性。我们计划研究222名社区居住的神经系统健康的老年人，进行动态血压和有氧健身的基线测试，基线和两年随访的结构和扩散张量磁共振成像（MRI）扫描，APOE基因分型，以及使用一系列标准化神经心理学测试进行的基线和两年随访的认知功能评估。我们将使用区域单变量和多变量网络分析方法以及基于体素的MRI形态测量来检验假设，以确定与衰老相关的灰色和白色物质的基线和两年纵向变化;以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基因型改变衰老中基线和两年纵向灰质和白色物质变化的区域分布和严重性;并评估通过衰老与健康状况和认知障碍遗传风险的交互作用识别的特定大脑区域如何与基线和两年认知下降相关。预计这项研究的结果将显著增强我们对与衰老和相关认知下降相关的大脑变化的理解，有助于识别那些与年龄相关的认知功能障碍风险最大的人，并为开发和测试重点策略提供基础，以延迟或预防导致衰老认知下降的大脑变化。

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.