The Contribution of Repetitive Head Impacts and Social Determinants of Health to Alzheimer's Disease and Related Dementia in Older Adult Black Men

重复性头部撞击和健康的社会决定因素对老年黑人阿尔茨海默病和相关痴呆症的影响

• 批准号: 10740485
• 负责人: Robert W. Turner
• 金额: $ 129.35万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740485
• 关键词: Accelerometer; Adult; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Atrophic; Biological Assay; Biological Markers; Black American; Black Populations; Black race; Blood; Boston; Brain; Cerebrospinal Fluid; Childhood; Cognition; Cognitive; Collaborations; Data; Data Set; Detection; Diagnosis; Diffusion; Disease; Disparity; Dose; Economics; Education; Elderly; Enrollment; Environment; Equation; Exposure to; Face; Frequencies; Goals; Health; Hippocampus; Impaired cognition; Individual; Late Effects; Life; Light; Link; Magnetic Resonance Imaging; Manufactured football; Mediating; Modeling; Neighborhoods; Nerve Degeneration; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurologic; Neurological outcome; Outcome; Participant; Pathway interactions; PhenX Toolkit; Plasma; Play; Positioning Attribute; Poverty; Proteins; Publishing; Questionnaires; Research; Resistance; Risk; Risk Factors; Role; Severities; Surveys; Tauopathies; Testing; Traumatic Brain Injury; Underrepresented Populations; Universities; Washington; Wellness Program; White Matter Hyperintensity; adverse childhood events; black men; brain health; chronic traumatic encephalopathy; cognitive function; contact sports; dosage; education access; experience; head impact; health care availability; health care quality; indexing; instrument; men; nervous system disorder; neurofilament; neuropsychiatric symptom; neuropsychiatry; racial disparity; racial identity; recruit; resilience; response; social factors; social health determinants; tau-1; white matter

ABSTRACT. Black Americans face nearly double the risk of Alzheimer’s disease (AD) and related compared to Whites. Black American men may be at increased risk for late-life neurological disorders associated with exposure to repetitive head impacts (RHI) and traumatic brain injury (TBI) from contact sports participation and other risk factors. Exposure to RHI/TBI is linked with late-life cognitive impairment, neuropsychiatric disturbances, and structural brain changes. Black racial identity and exposure to RHI/TBI has been shown to have an additive effect on MRI metrics of atrophy and cerebrospinal fluid neurodegenerative disease proteins. These neurological disparities might be explained by social determinants of health (SDOH) (e.g., education access and quality, health care access and quality, neighborhood environment), which might affect resistance and resilience to other neurological disorders from RHI/TBI. SDOH factors might indeed contribute to neurological outcomes in adult Black men irrespective of RHI/TBI. Yet, there has been persistent under- representation of Blacks in biomedical and health research, including among studies of the late effects of RHI from American football play. The overarching goal of this study is to examine the impact of RHI/TBI from American football and the contribution of early-life SDOH to later-life cognitive function, neuropsychiatric symptoms, structural MRI features, and plasma biomarkers in Black male former American football athletes and non-RHI/TBI exposed Black men. We will recruit 100 Black male former American football athletes (across all levels of play and cognitive continuum, 50+ years) and 100 age-matched Black males without RHI/TBI. Participants will enroll to complete harmonized cognitive and neuropsychiatric tests, MRI, and blood draw to assess neurodegenerative disease proteins. A battery of questionnaires (e.g., Adverse Childhood Experiences, Childhood-Experiences Survey, SHARELIFE survey) will be administered to assess SDOH. In Aim 1, we will investigate the association between RHI/TBI and later-life cognitive and neuropsychiatric symptoms in Black male former American football athletes. Aim 2 will investigate the association between RHI/TBI and later-life biomarkers of Aß, p-tau, and neurodegeneration outcomes in Black male former American football athletes. Aim 3 will examine the contribution of SDOH to later-life cognitive and neuropsychiatric symptoms and later-life biomarkers of Aß, p-tau, and neurodegeneration outcomes. Our hypotheses are that (1) RHI/TBI will be associated with worse cognitive and neuropsychiatric function and compromised structural gray/white matter in Black former football players; (2) impoverished SDOH will increase risk and reduce resilience to the late-life effects of RHI/TBI; and (3) impoverished SDOH will mediate the effects of RHI on late-life neurological outcomes. This R01 will discover the role of RHI/TBI and SDOH in older Black men. We will address racial disparities present in data on late life neurological outcomes from RHI/TBI to facilitate accurate disease detection and diagnosis at the individual-level.

摘要。美国黑人患阿尔茨海默病（AD）及相关疾病的风险几乎是美国黑人的两倍。 与白人相比。美国黑人男性可能会增加晚年神经系统疾病的风险 暴露于重复性头部撞击（RHI）和接触性运动引起的创伤性脑损伤（TBI） 和其他风险因素。暴露于RHI/TBI与晚年认知障碍、神经精神障碍有关。 干扰和大脑结构变化。黑人种族身份和暴露于RHI/TBI已被证明， 对萎缩和脑脊液神经退行性疾病蛋白的MRI指标具有累加效应。 这些神经学差异可以用健康的社会决定因素（SDOH）来解释（例如，教育 可获得性和质量、卫生保健可获得性和质量、社区环境），这可能会影响耐药性 以及对RHI/TBI引起的其他神经系统疾病的适应能力。SDOH因素可能确实有助于 成年黑人男性的神经系统结局，与RHI/TBI无关。然而，一直以来， 黑人在生物医学和健康研究中的代表性，包括在后期影响研究中的代表性 美国橄榄球比赛中的RHI本研究的总体目标是检查RHI/TBI的影响 从美式足球和早期生活的SDOH的贡献，以后的生活认知功能，神经精神 前美国橄榄球运动员黑人男性的症状、结构MRI特征和血浆生物标志物， 非RHI/TBI暴露的黑人男性。我们将招募100名黑人男性前美国足球运动员（在所有 游戏水平和认知连续性，50岁以上）和100名年龄匹配的黑人男性没有RHI/TBI。 受试者将入组完成统一的认知和神经精神测试、MRI和抽血， 评估神经退行性疾病蛋白。一组调查问卷（例如，不良童年经历， 将进行童年经历调查、SHARELIFE调查）以评估SDOH。在目标1中，我们 调查黑人RHI/TBI与晚年认知和神经精神症状之间的关系 前美国橄榄球运动员目的2将研究RHI/TBI与晚年生活的关系 黑人男性前美式橄榄球运动员中的ApoE、p-tau和神经变性结果的生物标志物。目的 3将检查SDOH对晚年认知和神经精神症状以及晚年生活的贡献。 生物标志物的Ablation，p-tau和神经退行性疾病的结果。我们的假设是（1）RHI/TBI将是 与认知和神经精神功能恶化以及结构性灰质/白色物质受损相关， 黑人前足球运动员;（2）贫困的SDOH将增加风险并降低对晚年的适应力 RHI/TBI的影响;（3）贫困的SDOH将介导RHI对晚年神经系统结局的影响。 这个R 01将发现RHI/TBI和SDOH在老年黑人男性中的作用。我们将解决种族不平等问题 在RHI/TBI的晚期神经学结局数据中呈现，以促进准确的疾病检测， 个人层面的诊断。