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

Abstract

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.