Project Summary/Abstract Tremendous growth in the prevalence of Alzheimer’s disease and related dementias (ADRD) is expected, with estimates indicating that by 2050 two-thirds of adults with ADRD will reside in low- and middle-income countries (LMICs). There is an urgent need to identify individuals at highest risk for ADRD at its earliest stages in order to better target prevention and early intervention strategies. While mild cognitive impairment (MCI) is intended to identify cognitively symptomatic individuals who are at greatest risk of progressing to dementia, most knowledge regarding the measurement of MCI, its risk factors, and its prognosis comes from high-income countries. In addition, MCI demonstrates significant variability in its course, given that large numbers of individuals with MCI either revert to cognitively normal or remain with a stable MCI diagnosis over time. Differences in life-course environmental determinants of cognitive health, biological risk, representativeness of study populations, MCI criteria, and cognitive measurement methods may contribute to this variability. Moreover, little is known from a global perspective about MCI measurement, its risk factors, and prognosis, particularly among LMICs which are expected to carry the greatest future ADRD burden. The overall goal of this study is to improve the cross-national measurement of MCI and to characterize its longitudinal course across populations with varied social, economic, cultural, and healthcare life experiences. Data from the Harmonized Cognitive Assessment Protocol (HCAP) Network offers a unique opportunity to generate harmonized MCI and dementia diagnoses and to investigate the course and predictors of MCI cross-nationally. We will use data from 3 studies with longitudinal HCAP data: the Health and Retirement (HRS) HCAP in the US; the Mexican Health and Aging Study’s (MHAS) ancillary study on cognitive aging (Mex-Cog); and the Longitudinal Aging Study in India–Diagnostic Assessment of Dementia (LASI-DAD). In Aim 1, we will harmonize MCI and dementia classifications cross-nationally and will compare the longitudinal prognosis of MCI across the US, Mexico, and India. In Aim 2, we will investigate the unique and shared sociodemographic, lifestyle, health, and biological risk factors associated with incident MCI and dementia across the US, Mexico, and India. In Aim 3, we will study the unique and shared cognitive and functional predictors of incident MCI and dementia risk cross-nationally and explore whether these predictors are consistent across levels of educational attainment, sex/gender, and literacy. This proposal will enhance the field of ADRD globally by improving the measurement of MCI and identifying the sociocultural and biological pathways to ADRD from MCI to aid in the early identification of individuals at most risk of dementia, for whom interventions should be prioritized.