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) 和社会经济地位较低的人 (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）。理解（a）是至关重要的 种族、成人社会经济地位以及它们之间（或与 生物性别）随着先前建立的磁共振成像（MRI）评估的变化， 早期 AD/ADRD 风险和加速大脑老化的临床前标志物； (b) 他们的生物心理社会 调解员； (c) 它们与认知能力下降的关系。与社区正在进行的健康老龄化有关 我们的辅助 HANDLS 扫描子研究显示，整个生命周期的多样性 (HANDLS) 队列研究显示 种族和社会经济地位与脑容量和白质（WM）疾病的协同关系。低社会经济地位赋予 AA 在 WM 病变负担方面的最大缺点；更高的SES赋予了显着的优势 对于全球和区域脑容量来说，是白人，但不是 AA。社会经济地位较低、AA 种族和/或他们的互动是 还与 WM 完整性较差以及额叶和默认模式下静息状态连接性减弱有关 网络。此外，种族和/或社会经济地位亚群体对选择的关系表现出不同的脆弱性 导致大脑和认知结果不佳的生物心理社会风险因素（例如糖尿病、饮食质量）。扩展 这些重要的横断面发现，我们建议对 238 名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、基线平均年龄 = 52 岁）进行评估 AD/ADRD 风险的 MRI 标记物 8-10 年的变化和大脑加速老化，确定多级介质 这种变化及其与认知能力下降的协变。具体来说，我们将：（1）检查交互性 种族、社会经济地位（和性别）与（a）先前确定的基于 MRI 的总结中的预期变化的关系 反映 AD 样萎缩模式的指数 [识别早期阿尔茨海默病的异常空间模式 疾病（SPARE-AD）]；加速脑老化相关萎缩模式[萎缩的空间模式 大脑衰老的识别（SPARE-BA）]；区域 WM 病变的数据驱动组件，用于评估位置 小血管疾病的特定负担；脑血流量、结构和功能连接； (2) 检查这些关系的生物心理社会中介因素，以及与认知功能的纵向协变；和 (3) 在结构 MRI、扩散张量成像、动脉自旋标记等领域应用多模态数据融合 静息态功能磁共振成像（fMRI），通过 SES（以及性别种族）大脑结构-功能关系来表征种族的基线， 并利用总体汇总指数作为后续措施中社会人口统计变化的预测因子 SPARE-AD、SPARE-BA 和额叶 WMLV 和认知能力下降。了解差异模式， 种族、SES（和/或性别）与临床前 MRI 标记的多水平预测因子和认知相关性 AD/ADRD 风险和加速的大脑老化将促进采取适当的预防和干预策略 减少并最终消除 AD/ADRD 相关的健康差异。