Sex differences in the confounders influencing the relationships linking socioeconomic factors and cognitive performance with family history of Alzheimer's disease and related dementias

Abstract

INTRODUCTION: Limited information is available regarding sex differences in the relationship of socioeconomic status and cognitive performance with Alzheimer's disease and related dementias (ADRD) family history. METHODS: Leveraging the UK Biobank (N = 448,100) and All of Us Research Program (N = 240,319), we conducted observational and genetically informed analyses to test the sex-specific associations of socioeconomic factors and cognitive performance with ADRD and its family history. RESULTS: Observational and genetically informed analyses highlighted that higher socioeconomic status and cognitive performance were associated with reduced ADRD and sibling–ADRD family history. Conversely, these were associated with increased parent-ADRD family history. Sex differences in these relationships were also identified. Additionally, although their sample size was limited, population minorities showed different patterns with respect to ADRD versus parent–ADRD family history. DISCUSSION: This study highlights sex differences in the misestimated associations of ADRD family history that appear to be related to socioeconomic factors and cognitive performance. Highlights: Alzheimer's disease family history is differently linked to socioeconomic factors. Observational and genetic analyses highlighted sex differences in these dynamics. Cause–effect relationships could contribute to biases in Alzheimer's disease assessment.