Cerebral Small Vessels in Motor and Cognitive Decline: Neuroimaging Signatures of Vulnerability & Resilience

摘要 脑部磁共振成像中日益普遍的脑白质高信号(WMH)显著 与血管风险因素有关，并与年龄相关的活动能力和认知障碍有关。然而，不是 每个WMH患者都同样受到影响，一些年长的人能够保持他们的行动能力和 尽管WMH对他们的大脑核磁共振造成了沉重的负担，但他们的认知能力仍然很差。我们不知道哪些特定的属性 这些人有助于他们的韧性。确定哪些特定因素与认知相关 在WMH存在的情况下，脆弱性和/或弹性对于有利地影响大脑的轨迹至关重要 我们老龄化人口的健康，特别是健康差距人口的健康。在过去的5年里，我们有 能够识别与血管风险因素、步态和中年认知相关的神经成像特征。 在这些发现的基础上，我们现在建议继续我们的调查并确定神经成像 患有WMH的中老年患者的步态和认知表现相关特征 特别关注非裔美国人和女性，他们都有患腰腿痛、步态和 认知障碍，但在这类研究中往往被低估。在Aim1中，我们将描述 正常外观白质与静息脑功能网络的扩散特性 患有WMH的中老年个体的联系。这些是我们拥有的神经成像特征 已经在我们的中年队列研究中确定了。在目标2中，我们将确定 中晚期NAWM和静息脑功能网络连接改变与步态和认知的关系 患有WMH的生命个体。AIM3是一个探索性目标，目的是确定与维护相关的其他属性 在脑部MRI上显示WMH的中老年个体的步态和认知表现。调查结果来自 拟议的工作将服务于两个总体目标。首先，确定了与 WMH患者的步态和认知表现将有助于指导治疗决策和分配 未来临床试验的适当WMH患者名单。第二，确定了神经成像特征 与步态和认知脆弱性和/或恢复力相关的WMH将揭示潜在的 机制和促进未来以减缓进展为目标的治疗开发的可能性 阿尔茨海默病和相关痴呆症(ADRD)的表达与行动能力受损 有风险的个人。

SUMMARY White matter hyperintensities (WMH), which are increasingly more prevalent on brain MRIs, are significantly associated with vascular risk factors and linked to age-related mobility and cognitive impairment. However, not everyone with WMH is equally afflicted and some older individuals are able to maintain their mobility and cognition despite a significant burden of WMH on their brain MRI. We do not know what specific attributes of these individuals contribute to their resilience. Identifying which specific factors are associated with cognitive vulnerability and/or resilience in the presence of WMH is critical for favorably impacting the trajectory of brain health in our aging population, especially among health disparity populations. Over the past 5 years we have been able to identify neuroimaging features associated with vascular risk factors, gait and cognition in midlife. Building on these findings, we now propose to continue our line of inquiry and identify the neuroimaging features associated with gait and cognitive performance in mid- to late-life individuals with WMH, with a specific focus on African Americans and women, both of whom are at a high risk for developing WMH, gait and cognitive impairment, but have often been under-represented in such studies. In Aim1, we will characterize the diffusion properties of the normal appearing white matter (NAWM) and resting brain functional network connections in mid- to late-life individuals who have WMH. These are the neuroimaging features that we have already identified in our midlife cohort study. In Aim 2 we will determine how changes in diffusion properties of NAWM and resting brain function network connections change in relation to gait and cognition in mid- to late life individuals with WMH. Aim3 is an exploratory aim to identify other attributes associated with maintaining gait and cognitive performance in mid- to late-life individuals who display WMH on brain MRI. Findings from the proposed work, will serve two overarching objectives. First, identified neuroimaging features that associate with gait and cognitive performance in individuals with WMH will help guide treatment decisions and allocation of appropriate individuals with WMH for future clinical trials. Second, identified neuroimaging features that associated with gait and cognitive vulnerability &/ or resilience in the presence of WMH will reveal underlying mechanisms and facilitate the future possibility of therapeutic development targeted at mitigating progression to impaired mobility and dementia and expression of Alzheimer’s Disease and related Dementias (ADRD) in at- risk individuals.