Effects of White and Gray Matter Integrity on Cognition in A Multi-Ethnic Cohort

项目摘要 种族和少数民族中与种族相关的认知障碍是最重要的公共卫生问题之一， 在美国的问题。65岁及以上的成年人数量预计在未来四年内将翻一番 几十年来，西班牙裔/拉丁裔或非西班牙裔黑人老年人的比例预计也将增加 迅速西班牙裔/拉丁美洲人和非西班牙裔黑人患认知障碍的风险更大， 非西班牙裔白人，这可能是由于这些群体中血管危险因素的负担更大。血管 风险因素可能影响宏观和微观结构WM的完整性，这可能反过来损害灰质 (GM)并导致认知障碍。虽然WM完整性的全球指标，如白色物质 越来越多的证据表明，高信号体积（WMHV）与认知广泛相关 WMHV不能反映WM疾病的全部程度。最近的研究表明，WM的半影 损伤存在于WMH之外，并且通过微结构WM完整性的度量更好地反映。尽管有这些 研究结果，宏观和微观结构WM完整性，GM完整性和认知之间的关系是 在具有更大血管风险因素的西班牙裔/拉丁美洲裔和非西班牙裔黑人人群中尚未充分了解 与白种人相比，脑血管和认知疾病的负担和风险增加。在这 建议的研究，我将调查宏观和微观结构WM完整性，GM之间的关联 在大多数西班牙裔/拉丁裔、临床上无卒中的北方曼哈顿研究中， （NOMAS）。中心假设是，MRI衍生的，区域特定的宏观和微观结构指标 工作记忆完整性预测认知表现，并且GM完整性的区域特定度量部分地介导了这一点 协会我还假设，微观结构的WM完整性的指标将与认知 独立于宏观结构WM完整性的度量并且比宏观结构WM完整性的度量更鲁棒。结果从这个提议 研究将为这些高危人群的潜在干预目标提供证据。 这些研究目标支持国家神经疾病和中风研究所（NINDS）的关键目标。 战略计划，包括：a）对基础、转化和临床研究的全方位投资; B） 促进临床研究;以及c）建立数据驱动的程序，以确定未满足的科学需求 机会和公共卫生需要内和跨神经疾病。拟议的研究还 通过WM完整性的MRI指标探索大脑网络，解决了NIH BRAIN Initiative问题。

Project Summary Age-related cognitive impairment in racial and ethnic minorities is one of the most important public health issues in the US. The number of adults aged sixty-five and older is expected to double in the next four decades, and the proportion of Hispanic/Latino or non-Hispanic black older adults is also expected to increase rapidly. Hispanics/Latinos and non-Hispanic blacks have a greater risk of cognitive impairment compared to non-Hispanic whites, which could be due to a greater burden of vascular risk factors in these groups. Vascular risk factors may influence macro- and microstructural WM integrity, which may in turn damage gray matter (GM) integrity and lead to cognitive impairment. Though global metrics of WM integrity, such as white matter hyperintensity volume (WMHV), have been associated with cognition extensively, growing evidence suggests that WMHV does not reflect the full extent of WM disease. Recent studies propose that a penumbra of WM damage exists outside of WMH and is better reflected by metrics of microstructural WM integrity. Despite these findings, the relationships between macro- and microstructural WM integrity, GM integrity, and cognition are not well understood in Hispanic/Latino and non-Hispanic black populations with a greater vascular risk factor burden and increased risk for cerebrovascular and cognitive disease as compared to Caucasians. In this proposed study, I will investigate the associations between macro- and microstructural WM integrity, GM integrity, and cognition in the mostly Hispanic/Latino, clinically stroke-free Northern Manhattan Study (NOMAS). The central hypotheses are that MRI-derived, region-specific metrics of macro- and microstructural WM integrity predict cognitive performance, and region-specific metrics of GM integrity partially mediate this association. I also hypothesize that metrics of microstructural WM integrity will associate with cognition independently from and more robustly than metrics of macrostructural WM integrity. Results from this proposed study will provide evidence for potential targets for intervention in these at-risk populations. These study aims support key goals of the National Institute of Neurological Disorders and Stroke (NINDS) Strategic Plan, including: a) investment across the full spectrum of basic, translational, and clinical research; b) promotion of clinical research; and c) establishment of a data-driven process to identify unmet scientific opportunities and public health need within and across neurological disease. The proposed research also addresses the NIH BRAIN Initiative by exploring brain networks through MRI metrics of WM integrity.