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.

PROJECT NARRATIVE Lower socioeconomic status (SES) is associated with increased risk of earlier age-related cognitive decline and Alzheimer’s Disease (AD), although there is individual variation in this risk. We will examine individual brain networks and AD genetic risk of lower-SES middle-age adults (40-59), along with changes in measures of health (cumulative allostatic load), environment, and lifestyles to determine whether we can understand and predict subsequent cognitive decline (following 3.5 years), and its individual variation. This work will inform the understanding of brain resilience and vulnerability to cognitive decline prior to late stage clinical events.