This application from the University of Georgia (UGA) and Emory University requests support for a four-year research conference series to address critical scientific issues associated with reducing Alzheimer’s Disease and Related Dementia (ADRDhealth disparities in the United States. The conference series we propose rests on interdisciplinary research using a population disease framework, with specific attention to differences in pathways to neurodegenerative diseases among susceptible populations. Genetics and family/personal health histories are non-modifiable factors, and modifiable factors include a wide range of lifespan environmental exposures and lifestyle factors. The conference series focuses on increasing understanding about how genetic factors are operating in concert with environmental exposures, family and personal health histories, and lifestyle factors to produce interactions that enhance or mitigate risk of ADRD within and between those at higher risk for ADRD. These critical issues remain largely overlooked and are fundamental for increasing knowledge for disease modification using precision medicine and for pharmacologic and non-pharmacologic intervention development in high-risk populations in AD clinical trials. The 4 related specific aims of the series are: 1. To understand how the current evidence examines specific genes, individually or in combination, are differentially distributed among various groups, and are associated with higher risk or protection against LOAD between. 2. To describe how genetic risk may be modulated by factors such as epigenetics, age, sex, environmental exposures, lifestyle/diet, family and personal health histories, social, and demographic factors between and within various high-risk groups at disproportionate risk for LOAD. 3. To examine current knowledge about how comorbidities such as vascular diseases, diabetes, and mental health moderate or mediate the increase risk of ADRD in these populations. 4. To explore underlying theory, new findings, and innovative observation, instrument development and calibration for respondent or patient assessment, and measurement/analytic strategies to improve our understanding of the gene x environment interactions influencing ADRD risk and how methods may be modified or adapted for use in specific research applications with higher risk populations.