Early and life course socioeconomic adversity and dementia risk in Hispanics/Latinos

西班牙裔/拉丁裔的早期和生命历程社会经济逆境和痴呆风险

• 批准号: 10445900
• 负责人: Charles DeCarli
• 金额: $ 144.18万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10445900
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Behavioral; Biological; Biological Aging; Biological Markers; Blood Vessels; Brain; Brain Injuries; Childhood; Clinical; Cognitive aging; DNA Methylation; Data; Development; Disadvantaged; Distress; Economic Conditions; Elderly; Etiology; Failure; Fostering; Genetic; Genomics; Goals; Growth; Health; Height; Hippocampus (Brain); Hispanic; Hispanic Populations; Immigrant; Impaired cognition; Influentials; Investigation; Knowledge; Latino Population; Learning; Life; Life Cycle Stages; Link; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Modeling; Nerve Degeneration; Neurocognitive; Participant; Pathway interactions; Plant Roots; Plasma; Play; Population; Poverty; Research; Research Priority; Resources; Risk Factors; Role; Shapes; Site; Study of Latinos; Testing; Time; White Matter Hyperintensity; Work; apolipoprotein E-4; cardiometabolism; cognitive change; cognitive function; cohort; critical period; dementia risk; disadvantaged population; early life adversity; ethnic minority; experience; gray matter; health inequalities; high risk; insight; low and middle-income countries; methylation biomarker; middle age; neuroimaging; novel; psychosocial; racial and ethnic; resilience; social culture; social determinants; social health determinants; socioeconomic adversity; socioeconomic disadvantage; socioeconomic disparity; socioeconomics; symposium; tau Proteins; vascular injury

Although the clinical manifestations of Alzheimer’s disease and related dementias (ADRD) typically emerge in late life, early life/childhood risk factors play a role in their etiology. Because childhood is a period of brain plasticity and sensitivity to enduring environmental influences, early socio-economic adversities can affect brain development and maturation, fostering adverse cognitive changes later in life. Persisting poverty over the life course may exacerbate these effects. Furthermore, genomic research in ADRDs does not fully consider the social determinants of health that are robust causes of racial and ethnic ADRDs disparities. This research gap is particularly important for Hispanics, who experience widespread socio-economic adversities, and are at high risk of ADRD despite modest effect of ApoE4 on ADRD risk. The Study of Latinos Investigation of Neurocognitive Aging (SOL INCA) and its MRI neuroimaging study are ideally suited to elucidating health effects of life course socio-economic conditions given the large and richly characterized cohort with repeated neurocognitive, vascular, and socio-cultural assessments. We will leverage these unparalleled resources to understand how early and sustained adverse socioeconomic conditions shape risk of ADRD and the biological mechanisms that may explain these effects. We posit that early socio-economic adversity will be related to lower gray matter and hippocampal volumes, as a result of poverty-related exposures during key periods of brain development and maturation. Later, these early adversities can foster steeper aging-related trajectories of cognitive decline. Persisting adversities over the life course may also result in greater white matter hyperintensity (WMH), due to poor cardiometabolic control arising from social determinants common in disadvantaged populations. Longitudinal DNA methylation (DNAm) markers will provide novel insights about the biological mechanisms linking early and sustained socio-economic adversities and indicators of ADRD risk. ADRD-related biomarkers (MRI, plasma Amyloid, Tau and Neurodegeneration [ATN] and DNAm) will inform whether the pathways linking socio-economic adversity are related to neurodegeneration, vascular injury, and accelerated aging. The study will directly address NIA research priorities related to understanding the pathways by which socio-economic, socio-cultural and behavioral factors affect neurocognitive aging.

尽管阿尔茨海默氏病和相关痴呆症（ADRD）的临床表现通常会出现 晚期生活，早期/童年危险因素在其病因中起作用。因为童年是大脑时期 可塑性和对结束环境影响的敏感性，早期的社会经济逆境会影响 大脑发育和成熟，促进了以后生活中的不良认知变化。坚持贫穷 生活课程可能会加剧这些影响。此外，ADRD中的基因组研究并未完全考虑 健康的社会决定者是种族和种族差异的强大原因。这个研究差距 对于经历宽度社会经济逆境且高度的西班牙裔人来说，这一点尤其重要 尽管APOE4对ADRD风险有适度的影响，但ADRD的风险。拉丁美洲人调查的研究 神经认知衰老（SOL INCA）及其MRI神经影像学研究非常适合阐明健康 生命过程的影响社会经济状况，鉴于重复的较大而丰富的队列 神经认知，血管和社会文化评估。我们将利用这些无与伦比的资源来 了解社会经济条件的早期和持续广告如何影响ADRD和生物学的风险 可能解释这些影响的机制。我们肯定的是，早期的社会经济广告将与 由于关键时期与贫困相关的暴露，下灰质和海马体积 大脑发育和成熟。后来，这些早期的逆境可以促进钢人与衰老相关的轨迹 认知能力下降。在生活过程中持续存在的逆境也可能导致更大的白质 高强度（WMH），由于心脏代谢性差，由社会决定者常见于 弱势群体。纵向DNA甲基化（DNAM）标记将提供有关有关的新见解 与早期和持续的社会经济逆境和ADRD风险指标联系起来的生物机制。 与ADRD相关的生物标志物（MRI，血浆淀粉样蛋白，TAU和神经变性[ATN]和DNAM）将告知 关联社会经济广告的途径是否与神经变性，血管损伤和 加速衰老。该研究将直接解决与理解有关的研究重点 社会经济，社会文化和行为因素影响神经认知衰老的途径。