Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities

项目摘要/摘要 健康不是随机分布在人与人之间或空间上的：它追踪一种社会经济 从个人延伸到他们所居住的地区的坡度。个人和区域级别 社会经济劣势的属性赋予了广泛相关的身体上的风险 和神经认知健康结果。这种风险在中年尤其明显，当中年 神经认知老化的病理生理轨迹预测晚年痴呆的风险 开始加速。在这方面，我们提供了一些初步证据，表明个人- 地区层面的社会经济劣势与皮质组织体积减少和 白质完整性，显示正常萎缩和完整性的大脑形态方面 年龄减退与认知结果较差有关。联系社会经济的途径 加速神经认知老化的不利因素尚不清楚。最近的证据，包括 我们自己的，表明代谢因素可能起到了作用。发展新陈代谢的个体 综合征、糖尿病前期或2型糖尿病患者患上糖尿病加速的风险增加 神经认知老化。此外，我们最近的横断面研究结果表明，新陈代谢 危险因素有助于区域水平的劣势与脑形态的关联 在中年成年人中。在这里，我们的目标是通过纵向研究新陈代谢来扩展这项工作 将个人和区域水平的劣势与神经认知老化联系起来的途径 一年的中年时期。为此，我们建议重新评估300个样本的认知 我们收集了社会经济参数的基线测量的正常中年成年人， 9-10年前的代谢风险、脑形态和认知功能(随访时的平均年龄 =52)。我们的主要目标是检查个人和地区层面的社会经济衡量标准 劣势预示着大脑形态和认知功能的变化，这些变化会随着年龄的增长而下降 以及劣势与神经认知老化之间的关联是否可以通过代谢来解释 风险和相关的炎症。我们期待这项研究将有助于新的 认知老化差异的神经生物学知识。

Project Summary/Abstract Health is not randomly distributed across people or across space: it tracks a socioeconomic gradient that extends from individuals to the areas in which they live. Individual- and area-level attributes of socioeconomic disadvantage confer risk for a broad range of interrelated physical and neurocognitive health outcomes. This risk is especially apparent in midlife when pathophysiological trajectories of neurocognitive aging that predict risk for dementia in later life begin to accelerate. In this regard, we have provided some of the first evidence that individual- and area- level socioeconomic disadvantage associate with reduced cortical tissue volume and white matter integrity, aspects of brain morphology that show normative shrinkage and integrity loss with age in association with poorer cognitive outcomes. Pathways linking socioeconomic disadvantage to accelerated neurocognitive aging remain unclear. Recent evidence, including our own, suggests that metabolic factors may play a role. Individuals who develop metabolic syndrome, pre-diabetes or type 2 diabetes mellitus are at increased risk for accelerated neurocognitive aging. Furthermore, our recent cross-sectional findings suggest that metabolic risk factors contribute to the associations of area-level disadvantage with brain morphology among midlife adults. Here, we aim to extend this work by longitudinally examining metabolic pathways linking individual- and area-level disadvantage to neurocognitive aging across a 10 year period of midlife. For this purpose, we propose reassessing a sample of 300 cognitively normal midlife adults on whom we collected baseline measures of socioeconomic parameters, metabolic risk, brain morphology and cognitive function 9-10 years ago (mean age at follow-up = 52). Our primary aims examine whether individual- and area-level measures of socioeconomic disadvantage predict changes in brain morphology and cognitive function that decline with age and whether associations of disadvantage with neurocognitive aging are explained by metabolic risk and associated inflammation. We anticipate that this study will contribute to new knowledge to the neurobiology of disparities in cognitive aging.