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.</p>
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.</p>
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.</p>
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.</p>
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.</p>