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

项目总结 成年人的衰老通常伴随着认知能力的下降，早在中年，甚至在没有确诊疾病的情况下也是如此。中年痴呆和老年痴呆症的风险并不是随机分布在整个人群中的。较低的社会经济地位(SES)是阿尔茨海默病(AD)的危险因素，中年时可能表现出较差的认知能力，并且随着年龄的增长认知能力下降更大。然而，即使在类似的情况下，一些人似乎也具有韧性，在成年后多年表现出轻微的认知能力下降，而另一些人则经历了快速和早期的认知能力下降。这表明，即使在不利的环境中，也有潜在的因素可以修改或缓冲个人认知能力下降的风险。为了了解这些个体差异，本项目将从中低阶层的SES招募中年成年人(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。每个人的大脑功能网络将使用非侵入性功能脑成像(当受试者在休息和执行各种任务时)进行测量。大脑网络组织(系统隔离)的一项重要指标(系统隔离)，随年龄、认知和SES而变化，将被检查以确定它是否能预测一个人在随后3.5年内的认知衰退(分3次测量)。至关重要的是，还将在3.5年内收集3次量化被认为在不同SES之间变化的不同特征的指标(包括压力的生物标记物(恒定负荷)，以及环境和生活方式的指标)。这些测量将被纳入分析，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样本，以及对环境、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、锻炼频率和社交(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)确定个体的SES和他们的脑网络组织之间的中介；(2)考察脑网络组织在不断变化的生活条件下作为认知韧性或脆弱性的生物标志物；(3)确定AD的遗传风险是否缓和了上述观察到的关系。

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.