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

尽管阿尔茨海默病和相关痴呆(ADRD)的临床表现通常出现在 晚年、早期生活/儿童时期的危险因素在其病因中起作用。因为童年是大脑的一段时间 可塑性和对持久环境影响的敏感性，早期的社会经济逆境可能会影响 大脑发育和成熟，在以后的生活中培养不良的认知变化。持续的贫困 生命历程可能会加剧这些影响。此外，ADRDS的基因组研究没有充分考虑到 健康的社会决定因素是造成种族和民族ADRDS差异的重要原因。这一研究差距 对于拉美裔美国人来说尤其重要，他们经历了广泛的社会经济逆境，并处于兴奋状态 尽管ApoE4对ADRD风险的影响不大，但ADRD的风险。西语裔美国人调查研究 神经认知老化(SOL INCA)及其MRI神经成像研究非常适合于阐明健康状况 生活过程的社会经济条件的影响，考虑到具有丰富特征的大量重复队列 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 了解早期和持续的不利社会经济条件如何塑造ADRD的风险和生物学 可能解释这些效应的机制。我们假设早期的社会经济逆境将与 灰质和海马体体积降低，这是在关键时期与贫困有关的暴露造成的 大脑的发育和成熟。后来，这些早期的逆境可能会导致与衰老相关的轨迹变得更加陡峭 认知能力下降的症状。在生命过程中持续逆境也可能导致脑白质增多。 高强度(WMH)，由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)标记将提供关于 将早期和持续的社会经济逆境与抗灾风险指标联系起来的生物机制。 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)将提供信息 联系社会经济逆境的途径是否与神经变性、血管损伤和 加速衰老。这项研究将直接涉及NIA与理解 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.