Social Determinants and Brain Health in PSEN1 E280A Carriers vs Non-Carriers: A Colombian Cohort

Social determinants of health (SDOH), including education, socioeconomic status, place of residence, genetic risk, and perceived stress, influence brain health and Alzheimer's disease (AD), yet their role in genetically at-risk populations remains underexplored. This study examined the influence of SDOH on early brain health, specifically its cognitive dimension, in Colombian individuals from the world's largest kindred with autosomal dominant AD (ADAD) caused by the PSEN1 E280A mutation. Participants included 86 mutation carriers and 71 non-carriers. Brain health was assessed using the BHA_CS index from the TabCAT battery, and perceived stress using the PSS-14. Carriers showed significantly lower brain health and higher perceived stress than non-carriers. Multiple regression analyses identified genetic status, age, education, and place of residence as significant predictors of brain health, with higher education and urban residence associated with better performance. These results demonstrate that SDOH contribute to early cognitive variability even decades before clinical onset in ADAD.