Plasma β-hydroxybutyrate concentration, genetic risk, and the incidence of Alzheimer's disease: A prospective study of 261,933 participants

Background: We investigated whether plasma β-hydroxybutyrate levels, a genetic risk score for Alzheimer's disease, and their interaction are associated with incident Alzheimer's disease. Methods: Using data from the UK Biobank—a population-based cohort study of adults aged 40–69 years, we assessed associations between baseline plasma β-hydroxybutyrate level, genetic risk score for Alzheimer's disease, and incident Alzheimer's disease. Incident Alzheimer's disease data were collected through linked data from hospital admissions and death registries. Results: In total, 261,933 adults were included, 1978 of whom developed incident Alzheimer's disease. Plasma β-hydroxybutyrate concentrations were not independently associated with Alzheimer's disease incidence after adjusting for covariates, whereas a higher genetic predisposition was linked to increased Alzheimer's disease incidence. Interactions were observed between plasma β-hydroxybutyrate concentrations and genetic risk for Alzheimer's disease on Alzheimer's disease incidence (P < 0.001). Conclusions: Further studies are warranted to elucidate the impact of plasma β-hydroxybutyrate status on Alzheimer's disease incidence.