Socioeconomic Mediators of Adult Brain Network Resilience and Vulnerability to Cognitive Decline

项目摘要 成人衰老通常伴随着认知能力下降，早在中年甚至在没有诊断出疾病的情况下。中年衰退和老年痴呆症的风险在人群中并不是随机分布的。较低的社会经济地位（SES）是阿尔茨海默病（AD）的危险因素，可能在中年表现出较差的认知能力，以及跨年龄的认知能力下降。然而，即使在类似的条件下，一些人似乎随着年龄的增长而恢复，在成年后的许多年里表现出最小的认知下降，而另一些人则经历了快速和早期的认知下降。这表明，即使在不利的环境中，也有潜在的因素可以改变或缓冲个体认知能力下降的风险。为了了解这些个体差异，本项目将招募来自中低阶层SES的中年人（40-59岁），并在任何晚期临床事件之前测量他们的大脑和认知能力的变化。每个人的功能性大脑网络将使用非侵入性功能性大脑成像来测量（当受试者休息和执行各种任务时）。大脑网络组织（系统隔离）的一个重要指标，随着年龄，认知和SES的变化，将被检查，以确定它是否可以预测一个人的认知能力下降在随后的3.5年（测量3次）。重要的是，量化不同SES的不同特征的措施（包括压力的生物标志物（非稳态负荷），以及环境和生活方式的措施）也将在3.5年内收集3次。这些测量结果将被纳入分析，以确定它们如何与大脑网络组织相互作用，以及网络组织与随后的认知衰退之间的相互作用。数据收集将包括用于评估心脏代谢、神经内分泌和炎症功能的生物标本样本，以及环境、生活方式和心理社会功能的广泛测量。后者包括情绪、饮食质量、睡眠质量、运动频率和社交互动（使用智能手机应用程序管理）的隔日调查（生态瞬时评估）。我们的主要目标包括：（1）确定个体SES和他们的大脑网络组织之间的中介，（2）检查大脑网络组织作为改变生活条件下认知弹性或脆弱性的生物标志物，（3）确定AD的遗传风险是否调节上述观察到的关系。

PROJECT SUMMARY Adult aging is typically accompanied by cognitive decline, as early as middle-age and even in the absence of diagnosed disease. The risk of both middle-age decline and older-age dementia are not randomly distributed across the population. Lower socioeconomic status (SES) is a risk factor for Alzheimer’s disease (AD), likelihood of exhibiting poorer cognition in middle-age, and greater cognitive decline across age. However, even under similar conditions some individuals seem to age with resilience, exhibiting minimal cognitive decline through many years of adulthood, while others experience rapid and early declining cognition. This suggests there are underlying factors that modify or buffer an individual's elevated risk for cognitive decline even in disadvantaged environments. To understand these individual differences, the present project will recruit middle-age adults (40-59 years) from lower- to middle-class SES, and measure their brain and changes in cognitive ability prior to any late stage clinical events. Each individual’s functional brain network will be measured using non-invasive functional brain imaging (while subjects are at rest and during various tasks). An important measure of brain network organization (system segregation), which varies with age, cognition, and SES, will be examined to determine whether it can predict an individual’s cognitive decline over the subsequent 3.5 years (measured over 3 occasions). Critically, measures quantifying distinct features that are presumed to vary across SES (including biological markers of stress (allostatic load), and measures of environment and lifestyle) will also be collected 3 times over 3.5 years. These measurements will be incorporated into analyses to determine how they interact with both brain network organization, and the interaction between network organization and subsequent cognitive decline. Data collection will include bio-specimen samples for assessing cardio- metabolic, neuroendocrine, and inflammatory function, as well as extensive measurement of environments, lifestyle, and psychosocial function. The latter includes alternate-day surveys (ecological momentary assessment) of mood, diet quality, sleep quality, exercise frequency, and social interaction (administered using a smart-phone application). Our primary aims involve: (1) identifying mediators between an individual’s SES and their brain network organization, (2) examining brain network organization as a biomarker of cognitive resilience or vulnerability under changing life conditions, (3) determining whether genetic risk of AD moderates the above observed relationships.