Educational experiences and substance use are key exposures for cognitive impairment and Alzheimers Disease and Alzheimers Disease-Related Dementias (AD/ADRD) that arise in adolescence and young adulthood. Education is the strongest known protective factor for cognitive impairment and AD/ADRD risk. Substance use is a main risk factor for acute cognitive impairment, although there is less evidence regarding its role in AD/ADRD development. A combination of detailed data on life course substance use and cognitive data is needed. The Monitoring the Future (MTF) Panel study offers an unprecedented opportunity to examine how educational experiences and substance use from adolescence through adulthood are associated with midlife cognitive function. The MTF Panel study has been continuously funded by NIH since 1975 and follows a new nationally representative sample of 2,450 12th grade students each year. The panel currently includes 50 cohorts from every high school class from 1976 to 2025 (total N~120,000). Respondents are first surveyed as students in high school at modal age 18 and followed regularly throughout the life course; the oldest cohorts have been surveyed at age 65. The current proposal aims to examine educational experiences and substance use from adolescence through adulthood as risk factors for AD/ADRD by adding measures of cognitive function to the MTF Panel. The proposed cognitive measures have been developed and used by the Health and Retirement Study (HRS) and the Understanding America Study (UAS) for online administration. Web-based measures assessing memory, numeracy, executive functioning, word knowledge, and fluid intelligence, will be added to the MTF Panel as a Healthy Brains Module for N~9,600 eligible MTF Panel participants who will be ages 50, 55, 60, or 65 in 2026 and 2027. These participants were enrolled in the MTF Panel study at age 18 while in high school from 1979/1980 for those age 65 through 1994/1995 for those age 50, roughly corresponding to birth cohorts 1961-1977. We conservatively estimate obtaining cognitive testing data from N~5,800 participants. We will also capture a broad range of self-reported health behaviors and paradata on response time and keystroke errors. The studys specific aims are to examine: (1) adolescent and young adult educational experiences (self-reported) and education quality (from National Center for Educational Statistics [NCES] administrative data) in relation to midlife cognition assessed by the proposed Healthy Brains Module at ages 50 to 65, (2) substance use across the lifespan in relation to midlife cognition, and (3) sociodemographic moderators of the associations between education and substance use with midlife cognition. The proposed project will provide an exceptional data resource to examine risk and protective factors from adolescence through adulthood and subsequent midlife cognitive functioning in a large, national sample with longitudinal data across the life course.