Plasma metabolites in early adulthood are associated with midlife cognitive performance and brain tissue integrity in the CARDIA study.

Abstract

INTRODUCTION: Circulating plasma metabolites may serve as early indicators of midlife cognitive performance, but whether these associations are also reflected in midlife brain structure or white matter hyperintensity (WMH) burden remains unclear. METHODS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, we examined 575 plasma metabolites in early adulthood (Year 7; age [mean ± SD] 32 ± 3.6 years, N = 1,736) in relation to brain magnetic resonance imaging (MRI) and cognitive performance 23 years later (Year 30; age [mean ± SD] 55 ± 3.6 years, N = 646). RESULTS: Eleven metabolites were independently associated with cognition; five were also associated with total brain volume but none with WMH burden. In mediation analysis, total brain volume accounted for 8%-33% of metabolite-cognition associations. DISCUSSION: Plasma metabolites measured in early adulthood are associated with midlife cognitive performance and a subset is also associated with total brain volume, whereas no associations were observed with WMH burden, highlighting early-adult metabolic signatures as markers of midlife brain structural health.

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