Neuroanatomical Substrates of Aging & Cognitive Decline

描述（由申请人提供）：本研究的目的是研究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衰退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，它对认知能力（包括工作记忆、注意力和执行功能）很重要，而认知能力往往会随着年龄的增长而下降。在神经系统健康的老年人中，一些健康和遗传风险因素与认知能力下降和颞、顶叶、扣带、额叶皮质和白质区域的大脑异常有特别的关系。这些因素包括血压、有氧适能和载脂蛋白E (APOE) s4等位基因的差异，载脂蛋白E (APOE) s4等位基因是阿尔茨海默病的常见易感基因。健康和遗传风险因素可能与衰老的影响相互作用，以解释在社区生活的活跃老年人中普遍观察到的认知衰退和脑萎缩区域的异质性。我们计划研究222名社区居住、神经健康的老年人，包括动态血压和有氧适能的基线测试、基线和两年随访的结构和弥散张量磁共振成像（MRI）扫描、APOE基因分型，以及基线和两年随访的认知功能评估，使用一系列标准化的神经心理学测试。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质和白质的基线和两年纵向变化；确定年龄如何与三个潜在的修饰因素相互作用：a)血压，b)有氧适能，c) APOE基因型，以改变基线和两年纵向衰老中灰质和白质变化的区域分布和严重程度；并评估通过衰老与健康状况和认知障碍遗传风险的相互作用确定的特定大脑区域与基线和两年认知能力下降之间的关系。预期本研究结果将显著提高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，有助于识别与年龄相关的认知功能障碍风险最大的人群，并为开发和测试重点策略提供基础，以延缓或预防导致衰老的认知能力下降的大脑变化。

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.