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

非洲裔美国人(AA)和社会经济地位低(SES)的人患癌症的风险不成比例 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SES的不同预期关系，以及它们彼此(或与 生物性别)以及先前建立的改变、磁共振成像(MRI)评估、 早期AD/ADRD风险和脑老化加速的临床前标记物；(B)他们的生物心理社会 (C)它们与认知衰退的关系。与正在进行的健康老龄化有关的社区 寿命多样性(HANDLS)队列研究，我们的辅助HANDLS扫描子研究显示 RACE和SES与脑体积和白质(WM)疾病的协同关系。较低的经济局局长授予 在西医损害负担方面，AAS的最大劣势；较高的SES赋予以下实质性优势 白人，而不是AA，代表全球和地区的脑容量。较低的SES、AA竞赛和/或它们的交互作用 也与WM完整性较低以及正面和默认模式中的休眠状态连接性降低有关 网络。此外，RACE和/或SES子组对SELECT关系表现出不同的脆弱性 生物、心理和社会风险因素(如糖尿病、饮食质量)导致大脑和认知结果不良。在…上扩展 这些重要的横断面发现，我们建议对238例中风和痴呆症进行前瞻性随访。 免费HANDLS扫描参与者(42%的AAS，49%的低SES，55%的女性，基线平均年龄=52岁)进行评估 8-10年AD/ADRD风险和脑老化加速的MRI标志物的变化，确定多水平的介体 这种变化，以及它们与认知衰退的协变性。具体地说，我们将：(1)研究互动 种族、SES(和性别)与(A)先前确定的基于MRI的总结的前瞻性变化的关系 反映AD样萎缩模式的指标[识别早期阿尔茨海默病的异常空间模式 疾病(Sare-AD)]；与脑老化相关的加速萎缩模式[萎缩的空间模式 脑老化识别(Spare-BA)]；区域西医损伤的数据驱动组件，以评估位置- 小血管疾病的特定负担；脑血流以及结构和功能的连通性；(2) 检查这些关系的生物、心理和社会调节因素，以及与认知功能的纵向协变； (3)将多模式数据融合应用于结构MRI、扩散张量成像、动脉自旋标记以及 静息状态功能磁共振成像通过SES(和按性别划分的种族)脑结构-功能关系来表征基线上的种族， 并利用总体汇总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， 种族、SES(和/或性别)与临床前MRI标记物的多水平预测因素和认知相关性 AD/ADRD风险和脑老化加速将有助于采取适当的预防和干预策略 减少和最终消除AD/ADRD中相关的健康差距。

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.