Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities

中年神经认知差异的代谢和炎症途径

基本信息

批准号：
9531344
负责人：
Peter J Gianaros
金额：
$ 67.57万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-20 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9531344
关键词：
Address Adult Age Aging Alzheimer&apos s Disease Area Attention Behavioral Biological Brain Brain-Derived Neurotrophic Factor Censuses Cognitive Cognitive aging Communities Complement Dementia Disadvantaged Disease Dyslipidemias Education Elderly Environmental Impact Episodic memory Functional disorder Future Genetic Genotype Health Health behavior Hippocampus (Brain)Hydrocortisone Hypertension Impaired cognition Incidence Income Individual Inflammation Inflammatory Insulin Resistance Knowledge Life Link Longitudinal Studies Measurement Measures Mediating Mediator of activation protein Memory Metabolic Metabolic Pathway Metabolic syndrome Morphology Neurobiology Neurocognitive Neurocognitive Deficit Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Obesity Occupational Occupations Outcome Pathway interactions Play Population Prediabetes syndrome Process Public Health Race Research Risk Risk Factors Role Sampling Short-Term Memory Socioeconomic Factors Socioeconomic Status Surface Testing Thick Tissues Variant Work age related aging brain base behavioral health biobehavior brain morphology built environment cardiometabolism cognitive function cognitive testing depressive symptoms executive function follow-up functional disability gray matter health disparity indexing inflammatory marker middle age modifiable risk mortality neuroimaging pre-clinical premature psychologic psychosocial sex social social organization socioeconomic disadvantage socioeconomics white matter

项目摘要

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.

项目概要/摘要健康并不是随机分布在人群或空间上：它跟踪社会经济从个人延伸到他们居住的区域的梯度。个人和地区层面社会经济劣势的属性给广泛的相互关联的身体健康带来风险和神经认知健康结果。这种风险在中年时尤其明显预测晚年痴呆风险的神经认知衰老的病理生理学轨迹开始加速。在这方面，我们提供了一些初步证据，表明个人- 和地区水平的社会经济劣势与皮质组织体积减少有关白质完整性，大脑形态的各个方面，显示出正常的收缩和完整性随着年龄的增长而丧失与较差的认知结果相关。连接社会经济的途径加速神经认知老化的不利因素仍不清楚。最近的证据，包括我们自己的研究表明，代谢因素可能发挥了作用。新陈代谢旺盛的人综合征、糖尿病前期或 2 型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，代谢风险因素导致区域水平劣势与大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检查代谢来扩展这项工作将个人和地区层面的劣势与 10 年来的神经认知衰老联系起来的途径中年时期。为此，我们建议重新评估 300 名样本的认知能力我们收集了正常中年成年人的社会经济参数基线测量值， 9-10年前的代谢风险、大脑形态和认知功能（随访时的平均年龄） = 52）。我们的主要目标是检验个人和地区层面的社会经济指标是否不利因素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劣势与神经认知衰老的关联是否可以通过代谢来解释风险和相关炎症。我们预计这项研究将有助于新的认知老化差异的神经生物学知识。