Interplay between Socioeconomic Markers and Polygenic Predisposition on Timing of Dementia Diagnosis.

Abstract

OBJECTIVESIdentifying the interplay between socioeconomic markers (education and financial resources) and polygenetic predisposition influencing the time of dementia and the diagnosis of clinical Alzheimerʼs disease (AD) dementia is of central relevance for preventive strategies.DESIGNProspective cohort design.SETTINGThe English Longitudinal Study of Aging is a household survey data set of a representative sample.PARTICIPANTSA total of 7,039 individuals aged 50 years and older participated in the study. Of these, 320 (4.6%) were diagnosed with dementia over the 10‐year follow‐up.MEASUREMENTSPolygenic score (PGS) for Alzheimerʼs disease (AD‐PGS) was calculated using summary statistics from the International Genomics of Alzheimerʼs Project. An accelerated failure time survival model was used to investigate interactions between AD‐PGS and socioeconomic markers on the timing of dementia and clinical AD dementia diagnosis.RESULTSA one standard deviation increase in AD‐PGS was associated with an accelerated time to dementia diagnosis by 4.8 months. The presence of the apolipoprotein E gene (APOE‐ε4) was associated with an earlier dementia onset by approximately 24.9 months, whereas intermediate and low levels of wealth were associated with an accelerated time to dementia diagnosis by 12.0 months and 18.7 months, respectively. A multiplicative interaction between AD‐PGS and years of completed schooling in decelerating the time to clinical AD dementia by 3.0 months suggests educational attainment may serve as a protective mechanism against AD diagnosis among older people with a higher polygenic risk. Interaction between AD‐PGS and lower wealth accelerated the time to clinical AD dementia diagnosis by 21.1 to 24.1 months.CONCLUSIONSocioeconomic markers influence the time to dementia and clinical AD dementia diagnosis, particularly in those with a higher polygenic predisposition. J Am Geriatr Soc 68:1529‐1536, 2020.