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

运动和认知能力下降的大脑小血管：脆弱性的神经影像特征

• 批准号: 10446525
• 负责人: FARZANEH A SOROND
• 金额: $ 151.16万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10446525
• 关键词: African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Award; Basal Ganglia; Blood Pressure; Blood Vessels; Brain; Brain imaging; Cerebrum; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Coronary Artery Risk Development in Young Adults Study; Data; Dementia; Diffusion; Elderly; Epidemiology; Future; Gait; Healthcare; Healthcare Systems; Image; Impaired cognition; Impairment; Individual; Link; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Motor; Patients; Property; Publications; Publishing; Rest; Risk; Testing; Thalamic structure; Universities; Vascular Dementia; Walking; White Matter Hyperintensity; Woman; Work; age related; aged; aging brain; aging population; base; brain health; brain magnetic resonance imaging; cognitive function; cognitive performance; cognitive testing; cohort; data warehouse; disability; epidemiologic data; executive function; falls; health disparity populations; high risk; middle age; morphometry; negative affect; nervous system disorder; neuroimaging; preservation; prevent; recruit; resilience; therapeutic development; vascular risk factor; white matter; young adult

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.

总结 白色高信号（WMH）在脑MRI上越来越普遍， 与血管危险因素相关，并与年龄相关的运动和认知障碍有关。但并非 每个患有WMH的人都受到同样的折磨，一些老年人能够保持他们的流动性， 尽管WMH对他们的大脑MRI造成了重大负担，但他们的认知能力仍然很差。我们不知道具体的属性是什么， 这些人有助于他们的复原力。确定哪些特定因素与认知相关 WMH存在时的脆弱性和/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，特别是在健康差距人群中。在过去的五年里，我们 能够识别与中年血管危险因素、步态和认知相关的神经影像学特征。 基于这些发现，我们现在建议继续我们的调查路线，并确定神经影像学 与中晚期WMH患者的步态和认知表现相关的特征， 特别关注非洲裔美国人和妇女，他们都有患WMH、步态和 认知障碍，但在这些研究中往往代表性不足。在目标1中，我们将描述 正常外观白色物质（NAWM）和静息脑功能网络的弥散特性 中晚期WMH患者之间的联系。这些是我们所拥有的神经成像特征 已经在我们的中年队列研究中发现了。在目标2中，我们将确定 NAWM和静息脑功能网络连接在中后期与步态和认知相关的变化 与WMH一起生活的人。目标3是一个探索性的目标，以确定与维护 步态和认知表现在中年到晚年的人谁显示WMH的大脑MRI。的结果 拟议的工作将服务于两个总体目标。首先，识别出与 WMH患者的步态和认知表现将有助于指导治疗决策和分配 合适的WMH患者用于未来的临床试验。第二，确定神经影像学特征， 与步态和认知脆弱性和/或弹性在WMH的存在将揭示潜在的 机制，并促进未来针对缓解进展的治疗开发的可能性 活动能力受损和痴呆以及阿尔茨海默病和相关痴呆（ADRD）在 风险个人。

项目成果

Diffusion Restriction in the Splenium: A Comparative Study of Cytotoxic Lesions of the Corpus Callosum (CLOCCs) versus Lesions of Vascular Etiology.

• DOI: 10.3390/jcm12226979
• 发表时间: 2023-11-08
• 期刊: Journal of clinical medicine
• 影响因子: 3.9

N-Terminal Pro Brain, N-Terminal Pro Atrial Natriuretic Peptides, and Dynamic Cerebral Autoregulation.

• DOI: 10.1161/jaha.120.018203
• 发表时间: 2020-10-20
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Mahinrad S;Sabayan B;Garner CR;Lloyd-Jones DM;Sorond FA
• 通讯作者: Sorond FA

Vascular health across young adulthood and midlife cerebral autoregulation, gait, and cognition.

青年期和中年大脑自动调节、步态和认知的血管健康。

• DOI: 10.1002/alz.12246
• 发表时间: 2021
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Mahinrad,Simin;Shownkeen,Meghana;Sedaghat,Sanaz;Yaffe,Kristine;Hausdorff,JeffreyM;Lloyd-Jones,DonaldM;Gorelick,PhilipB;Sorond,FarzanehA
• 通讯作者: Sorond,FarzanehA

Decline in kidney function over the course of adulthood and cognitive function in midlife.

成年期肾功能下降，中年认知功能下降。

• DOI: 10.1212/wnl.0000000000010631
• 发表时间: 2020
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Sedaghat,Sanaz;Sorond,Farzaneh;Yaffe,Kristine;Sidney,Stephen;Kramer,HollyJ;JacobsJr,DavidR;Launer,LenoreJ;Carnethon,MercedesR
• 通讯作者: Carnethon,MercedesR

Cumulative Blood Pressure Exposure, Basal Ganglia, and Thalamic Morphology in Midlife.

• DOI: 10.1161/hypertensionaha.120.14678
• 发表时间: 2020-05
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Jenkins LM;Garner CR;Kurian S;Higgins JP;Parrish TB;Sedaghat S;Nemeth AJ;Lloyd-Jones DM;Launer LJ;Hausdorff JM;Wang L;Sorond FA
• 通讯作者: Sorond FA