Metabolites and MRI-Derived Markers of AD/ADRD Risk in a Puerto Rican Cohort

Abstract

Abstract Objective Several studies have examined metabolomic profiles in relation to Alzheimer’s disease and related dementia (AD/ADRD) risk; however, few studies have focused on minorities, such as Latinos, or examined Magnetic-Resonance Imaging (MRI)-based outcomes. Methods We used multiple linear regression, adjusted for covariates, to examine the association between metabolite concentration and MRI-derived brain age deviation. Metabolites were measured at baseline with untargeted metabolomic profiling (Metabolon, Inc). Brain age deviation (BAD) was calculated at wave 4 (~ 9 years from Boston Puerto Rican Health Study (BPRHS) baseline) as chronologic age, minus MRI-estimated brain age, representing the rate of biological brain aging relative to chronologic age. We also examined if metabolites associated with BAD were similarly associated with hippocampal volume and global cognitive function at wave 4 in the BPRHS. Results Several metabolites, including isobutyrylcarnitine, propionylcarnitine, phenylacetylglutamine, phenylacetylcarnitine (acetylated peptides), p-cresol-glucuronide, phenylacetylglutamate, and trimethylamine N-oxide (TMAO) were inversely associated with brain age deviation. Taurocholate sulfate, a bile salt, was marginally associated with better brain aging. Most metabolites with negative associations with brain age deviation scores also were inversely associations with hippocampal volumes and wave 4 cognitive function. Conclusion The metabolites identified in this study are generally consistent with prior literature and highlight the role of BCAA, TMAO and microbially derived metabolites in cognitive decline.