Prospective Change in Preclinical MRI Markers of ADRD Risk and Brain Aging by Race, Socioeconomic Status, and Sex

ADRD 风险和脑衰老的临床前 MRI 标志物的前瞻性变化（按种族、社会经济状况和性别划分）

• 批准号: 10671861
• 负责人: Shari Waldstein
• 金额: $ 86.26万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10671861
• 关键词: Adult; African American population; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Atrophic; Behavioral; Biological; Biological Markers; Brain; Brain imaging; Cerebrovascular Circulation; Cerebrum; Cognition; Cognitive; Cohort Studies; Communities; Data; Dementia; Detection; Diabetes Mellitus; Diet; Diffusion Magnetic Resonance Imaging; Disadvantaged; Discrimination; Disease; Environmental Risk Factor; Functional Magnetic Resonance Imaging; Image; Impaired cognition; Intervention; Knowledge; Lesion; Link; Location; Longevity; Machine Learning; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Memory; Memory Loss; Methods; Microvascular Dysfunction; Modality; Modeling; Neighborhoods; Neurocognitive; Outcome; Participant; Pattern; Perfusion; Persons; Poverty; Prevention; Psychosocial Factor; Public Health; Race; Race Relations; Research; Research Personnel; Resources; Rest; Risk; Risk Factors; Risk Marker; Scanning; Socioeconomic Status; Stroke; Structure; Subgroup; Time; Variant; White Matter Disease; Woman; aging brain; arterial spin labeling; base; biological sex; biopsychosocial; brain health; brain volume; cerebral atrophy; cognitive function; data fusion; data modeling; dementia risk; design; disability; executive function; follow-up; gray matter; health disparity; healthy aging; high risk population; imaging biomarker; imaging modality; improved; indexing; low socioeconomic status; mRNA Differential Displays; marginalized population; multimodal data; neuroimaging; nutrition; pre-clinical; preventive intervention; primary outcome; prognostic; prospective; psychologic; rate of change; recruit; secondary outcome; sex; social; sociodemographic disparity; sociodemographic predictors; synergism; white matter

African Americans (AA) and those with low socioeconomic status (SES) are at disproportionate risk for Alzheimer’s disease-associated dementia (AD) and related dementias (ADRD). It is crucial to understand (a) differential prospective relations of race, adult SES, and their interaction with one another (or with biological sex) with change in previously established, magnetic resonance imaging (MRI) assessed, preclinical markers of early AD/ADRD risk and accelerated brain aging; (b) their biopsychosocial mediators; and (c) their relation to cognitive decline. Linked to the ongoing Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort study, our ancillary HANDLS Scan substudy showed synergistic relations of race and SES to brain volumes and white matter (WM) disease. Low SES conferred the greatest disadvantage to AAs for WM lesion burden; and higher SES conferred substantial advantage to Whites, but not AAs, for global and regional brain volumes. Lower SES, AA race, and/or their interaction were also related to lesser WM integrity, and diminished resting state connectivity in frontal and default mode networks. Further, race and/or SES subgroups displayed differential vulnerability to the relations of select biopsychosocial risk factors (e.g., diabetes, diet quality) to poor brain and cognitive outcomes. To expand upon these important cross-sectional findings, we propose a prospective follow-up of the 238 stroke-and dementia- free HANDLS Scan participants (42% AAs, 49% low SES, 55% women, mean age = 52 at baseline) to assess 8-10 year change in MRI markers of AD/ADRD risk and accelerated brain aging, identify multi-level mediators of such change, and their covariation with cognitive decline. Specifically, we will: (1) examine interactive relations of race, SES (and sex) with (a) prospective change in previously identified MRI-based summary indices reflecting AD-like atrophy patterns [Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s Disease (SPARE-AD)]; accelerated brain aging-related atrophy patterns [Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA)]; data-driven components of regional WM lesions to assess location- specific burden of small vessel disease; cerebral blood flow, and structural and functional connectivity; (2) examine biopsychosocial mediators of these relations, and longitudinal covariation with cognitive function; and (3) apply multi-modal data fusion across structural MRI, diffusion tensor imaging, arterial spin labeling, and resting state fMRI to characterize race by SES (and race by sex) brain structure-function relations at baseline, and utilize the overall summary indices as predictors of sociodemographic variation in follow-up measures of SPARE-AD, SPARE-BA, and frontal WMLV and cognitive decline. Understanding the differential patterns, multi-level predictors, and cognitive correlates of race-, SES- (and/or sex) with preclinical MRI markers of AD/ADRD risk and accelerated brain aging will facilitate appropriate strategies in prevention and intervention for the reduction and ultimate elimination of related health disparities in AD/ADRD.

非裔美国人（AA）和社会经济地位低的人（SES）面临不成比例的风险， 阿尔茨海默病相关痴呆（AD）和相关痴呆（ADRD）。关键是要理解（a） 不同的种族，成人SES的前瞻性关系，以及他们相互之间的相互作用（或 生物学性别）与先前确定的变化，磁共振成像（MRI）评估， 早期AD/ADRD风险和加速脑老化的临床前标志物;（B）其生物心理社会学 调解人;和（c）他们的关系，认知能力下降。与正在进行的社区健康老龄化有关， 我们的辅助HANDLS扫描子研究显示， 种族和SES与脑容量和白色物质（WM）疾病的协同关系。社会经济地位低， 对于WM病变负荷，AA的最大劣势; SES较高， 白色，但不是AA，用于全球和区域脑容量。较低的SES，AA种族，和/或他们的相互作用是 也与WM完整性降低以及额叶和默认模式下静息状态连接减少有关 网络.此外，种族和/或SES亚组显示出对选择关系的差异脆弱性， 生物心理社会风险因素（例如，糖尿病、饮食质量）与大脑和认知功能不良的关系。展开 这些重要的横断面研究结果，我们建议对238例中风和痴呆患者进行前瞻性随访， 免费HANDLS扫描参与者（42% AA，49%低SES，55%女性，基线时平均年龄= 52岁）进行评估 8-10 AD/ADRD风险和加速脑老化的MRI标志物的年变化，确定多水平介质 以及它们与认知能力下降的协变。具体而言，我们将：（1）研究互动 种族、SES（和性别）与（a）先前确定的基于MRI的摘要中的预期变化的关系 反映AD样萎缩模式的指标[用于早期阿尔茨海默病识别的异常空间模式 疾病（SPARE-AD）];加速性脑老化相关萎缩模式[ 脑老化的识别（SPARE-BA）];区域WM病变的数据驱动组件，以评估位置- 小血管疾病的特定负担;脑血流量以及结构和功能连接;（2） 检查这些关系的生物心理社会中介，以及与认知功能的纵向协变; (3)在结构MRI、扩散张量成像、动脉自旋标记中应用多模式数据融合， 静息状态功能磁共振成像以表征基线时SES种族（和性别种族）脑结构-功能关系， 并利用总体概括指数作为社会人口学变化的预测因子， SPARE-AD、SPARE-BA和额叶WMLV与认知功能下降。了解不同的模式， 多水平预测因子，以及种族、SES（和/或性别）与临床前MRI标志物的认知相关性， AD/ADRD风险和加速的脑老化将促进适当的预防和干预策略 减少并最终消除AD/ADRD中的相关健康差异。