PROJECT SUMMARY Alzheimer's disease and related dementias (ADRD) disproportionately affect Black and Hispanic adults, attributable, in part, to disparities in socioeconomic status and age-related health conditions. ADRDs are among the costliest dis- eases to treat, posing a profound burden for people already experiencing health disparities. Mass incarceration, which disproportionately affects Black and Hispanic people, may play a key role. We propose to extend our current 28-year longitudinal study, the Northwestern Juvenile Project (NJP), to conduct the first comprehensive, prospective study of how the dose of incarceration—frequency and duration of stays, type of facility (juvenile detention, jail, prison), age(s), and recency—affects health, age-related conditions, and risk factors for ADRD. Leveraging our orig- inal sample (n=1829 (now 1492), who will be ages 39-49 in the proposed study), we will use a mixed-methods ap- proach, focusing on modifiable, midlife risk factors for ADRD as noted in the Lancet Commission 2020 report on ADRD prevention and other risk indexes: hypertension, smoking, obesity, depression, exercise, diabetes, social con- tact, and alcohol abuse. Middle adulthood (40+ years) is a critical developmental period for targeting ADRD risk factors. We have already conducted a pilot study (n=65) that demonstrates the feasibility of the proposed methods and the need to study health, age-related conditions, and risk factors for ADRD in people who have been incarcer- ated. We will: (1) Interview participants to assess physical and mental health, psychological well-being, and cogni- tion using the NIH Toolbox (crystallized and fluid intelligence) and the Uniform Data Set (memory); (2) Collect blood-based biomarkers of health (glucose metabolism, lipid ratios, kidney function, inflammation, and biological aging); (3) Collect physiological measurements of health (height, weight, waist circumference, blood pressure, rest- ing heart rate); and (4) Use detailed data on dose of incarceration and the framework of dose-response models to as- sess how incarceration affects health, age-related conditions, and risk factors for ADRD. We have 3 specific aims: (1) To assess health, age-related conditions, and ADRD risk factors among participants at median age 45 and com- pare them to participants in the Add Health study, an NIA-funded study with a similarly aged sample; (2) To exam- ine the relationship between the dose of incarceration and health, age-related conditions, and risk factors for ADRD; and (3) To identify risk and protective factors—including geocoded addresses to determine environmental risks— that moderate the relationship between dose of incarceration and health, age-related conditions, and ADRD risk fac- tors. We hypothesize, for example: that our participants will have worse health than those in Add Health; that per- sons who cycle in and out of jail will demonstrate poorer health and greater risk for ADRD than persons with long ...