Social-biological dimensions of ADRD risk and resilience in a Native American cohort

项目摘要/摘要 这项名为《痴呆症压力和韧性扩展》(STRIDE)的研究在中西部部落社区的一群中老年成员中探索了与认知和脑源性阿尔茨海默病及相关痴呆症(ADRD)标记物相关的可改变的社会-生物学途径。ADRD的发病率和流行率在各个社会人口阶层都在上升，但社会劣势加剧了风险，强有力的证据表明，非裔美国人和美国印第安人/阿拉斯加原住民(AI/AN)人口承担着特别高的ADRD负担。社会和种族在认知老化方面的差异显然是多因素的，但目前解释不足。包括种族、地理和社会经济地位在内的相互交错的劣势标记与长期暴露于可引起神经内分泌和血管功能障碍的应激源相关，并导致发病率和年龄相关下降的过早发生。然而，人工智能/人工智能社区在认知老化研究中的代表性仍然严重不足，而且还没有探索过将社会环境逆境与ADRD相关的大脑和认知变化联系起来的“风化”过程。促进韧性的社会资源也是未知的。这一STRIDE项目的长期目标是阐明在服务不足的人工智能/AN社区中，社会劣势导致ADRD风险的机制，并确定特定于社区的个人、社会和结构性资源，以减轻这种风险。这项试点研究的短期目标是在一群AI/AN社区成员中确定与ADRD标记相关的社会和生物因素，并建立初步的方法和数据，以促进未来以复原力为重点的研究。Stride建立在部落老龄委员会和威斯康星州阿尔茨海默病研究中心(ADRC)之间的合作伙伴关系基础上，并利用ADRC提供的丰富现有认知和生物标记物数据。多维应激数据的收集，包括自我报告的负担和经过验证的生理风化指数，允许初步模拟延长寿命的应激源和资源对与人口相关的ADRD标记的影响。目的1：在一组80名AI/AN参与者中，研究社会/生理应激指数与ADRD风险标记物之间的关系，包括(I)认知功能下降；(Ii)在AI/AN参与者的子组中，关键的ADRD生物标记物，如β-淀粉样蛋白42。目标2(探索性)：描述AI/AN人群突出的自我报告社会资源的特征，并检查(I)与ADRD标记的关系，以及(Ii)相关资源对目标1中的关系的修改。影响：实现STRIDE试点目标将建立认知健康的社区特定社会决定因素的方法和早期数据，并确定可作为未来风险降低研究的近期结果的压力相关生物介体。在这样做的过程中，STRIDE为越来越多的研究做出了贡献，这些研究试图认识、理解和减少AI/AN社区面临的日益严重的ADRD危机。

PROJECT SUMMARY/ABSTRACT This expansion of the Stress and Resilience in Dementia (STRIDE) study explores modifiable social-biological pathways associated with cognitive and brain-based Alzheimer’s disease and related dementia (ADRD) markers in a cohort of middle-aged and older members of a Midwestern tribal community. Incidence and prevalence of ADRD are rising across sociodemographic strata, but social disadvantage exacerbates risk and strong evidence suggests that African Americans and American Indian/Alaska Native (AI/AN) populations bear particularly high ADRD burden. Social and racial disparities in cognitive aging are clearly multifactorial but are currently underexplained. Intersecting disadvantage markers including race, geography, and socioeconomic status correlate with chronic exposure to stressors that can provoke neuroendocrine and vascular dysfunction and the premature onset of morbidity and age-related declines. However, AI/AN communities remain severely underrepresented in cognitive aging research, and “weathering” processes that plausibly link socioenvironmental adversity to ADRD-associated brain and cognitive changes have not been explored. Social resources that promote resilience are also unknown. The long-term goal of this STRIDE project is to elucidate mechanisms by which social disadvantage contributes to ADRD risk in an underserved AI/AN community, and to pinpoint community-specific individual, social, and structural resources that mitigate that risk. The short-term objective of this pilot study is to identify social and biological factors associated with ADRD markers in a cohort of AI/AN community members, and establish preliminary methods and data that will facilitate future resilience-focused research. STRIDE builds on a partnership between the tribal Commission on Aging and the Wisconsin Alzheimer’s Disease Research Center (ADRC), and leverages rich existing cognitive and biomarker data available through the ADRC. The collection of multidimensional stress data including both self-reported burden and a validated index of physiological weathering allow for preliminarily modeling the influence of life-spanning stressors and resources on population-relevant ADRD markers. Aim 1: In a group of 80 AI/AN participants, examine relationships between social/physiological stress indices and markers of ADRD risk including (i) cognitive decline and (ii) in sub-set of AI/AN participants, key ADRD biomarkers such as β-amyloid42. Aim 2 (Exploratory): Characterize self-reported social resources salient to AI/AN populations and examine (i) relationships with ADRD markers and (ii) modification of relationships in Aim 1 by relevant resources. Impact: Achieving STRIDE pilot aims will establish methods and early data on community-specific social determinants of cognitive health, and identify stress-linked biological mediators that can serve as proximal outcomes in future risk reduction studies. In so doing, STRIDE contributes to a growing body of research that seeks to recognize, understand, and reduce the growing ADRD crisis facing AI/AN communities.