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

虽然阿尔茨海默病和相关痴呆症（ADRD）的临床表现通常出现在老年痴呆症患者中， 晚年、早年/儿童期的危险因素在其病因中起作用。因为童年是大脑发育的时期 可塑性和敏感性持久的环境影响，早期的社会经济逆境可以影响 大脑发育和成熟，在以后的生活中促进不利的认知变化。长期贫穷， 生命进程可能加剧这些影响。此外，ADRD的基因组研究没有充分考虑 健康的社会决定因素是种族和民族ADRD差异的重要原因。这一研究空白 对西班牙裔人来说尤其重要，他们经历了广泛的社会经济困境， 尽管ApoE 4对ADRD风险有适度的影响，但ADRD风险仍然存在。拉丁裔美国人调查研究 神经认知老化（SOL印加）及其MRI神经成像研究非常适合于阐明健康 生活过程中的社会经济条件的影响，考虑到大量的和丰富的特点的队列， 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， 了解早期和持续的不利社会经济条件如何影响ADRD的风险， 可以解释这些影响的机制。我们认为，早期的社会经济逆境将与以下因素有关： 较低的灰质和海马体积，由于贫困相关的暴露在关键时期， 大脑发育和成熟。后来，这些早期的逆境可以促进更陡峭的衰老相关轨迹 认知能力下降在生命过程中持续的逆境也可能导致更多的白色物质 高强度（WMH），由于常见的社会决定因素引起的心脏代谢控制不良， 弱势群体。纵向DNA甲基化（DNAm）标记将提供新的见解， 早期和持续的社会经济逆境与ADRD风险指标之间的生物学机制。 ADRD相关生物标志物（MRI、血浆淀粉样蛋白、Tau和神经变性[ATN]和DNAm）将告知 联系社会经济逆境的途径是否与神经退行性疾病、血管损伤和 加速老化这项研究将直接解决与了解有关的NIA研究优先事项， 社会经济、社会文化和行为因素影响神经认知老化的途径。

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.