Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term. Over the short-term, we hypothesize that engaging in URT will deplete attentional resources and result in worse cognitive performance in daily life. Over the long-term, we expect that the effects of chronic stress, from repeated exposure to stressors and regular engagement in URT, will be apparent in dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and inflammation. Over time, stress-related physiological dysregulation will result in accelerated cognitive decline. This study utilizes a prospective longitudinal measurement-burst design. A systematic probability sample of participants aged 25 to 65 is recruited from residents of the Bronx, NY. Consenting participants complete a baseline assessment and follow-up waves at 9, 18, and 27 months post-baseline. At each wave, participants complete a 14 day measurement burst of brief surveys and cognitive assessments delivered via study smartphones during daily life. Participants provide saliva samples four times each day for five days during the measurement burst and fasting blood samples at the end of each burst from which cortisol and dehydroepiandrosterone sulfate (DHEAS), circulating inflammatory markers, and stimulated inflammatory responses to lipopolysaccharide in whole blood are determined. This study takes a multi-pronged approach to assessing stress (i.e., early adversity, chronic strains, major events, daily hassles), psychological mediators (e.g., URT), biological mechanisms (i.e., HPA function, inflammation) and outcomes across different time-scales (i.e., momentary cognitive performance, cognitive decline across years). The systematic probability sample is locally representative and can be compared with national norms on key markers of health and well-being. The findings will improve our understanding of how environmental, psychological, and physiological stress-related influences accumulate to affect cognitive health and identify potential targets (e.g., URT, inflammation) for prevention and intervention promoting cognitive health.