Abstract 14493: Association of Circulating Ketone Bodies With Cognitive Performance and Dementia in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Introduction: There is growing interest in the association between circulating ketone bodies (KB) and cognitive function, especially in the context of aging and neurodegenerative diseases. Aim: To examine the prospective association of KB with cognitive performance and clinical dementia among participants without baseline cardiovascular disease (CVD). Methods: KB were measured in 6786 MESA participants by nuclear magnetic resonance spectroscopy at Exam 1 (2000-02). Plasma levels of the 3 ketone bodies (β-hydroxybutyrate, acetoacetate, and acetone) were summed as total KB. Cognitive performance was assessed in 4392 participants at Exam 5 (2010-12) by the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) tests and re-administered to a subset (n=1838) at Exam 6 (2016-18). We examined the association of total KB with Exam 5 cognitive test performance and with the change in scores from Exam 5 to Exam 6 using multivariable linear regression. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with incident dementia. Incident dementia was identified by ICD codes at hospitalization or death (2000-2018) Results: A total of 6786 participants were included in the analysis (mean age 62 (10) years at Exam 1, 53% women, 61% non-White). There were 585 incident dementia events over a median follow-up of 16.7 yrs. In a fully adjusted model, a doubling of total KB was associated with a greater risk of incident dementia [HR (95% CI): 1.21 (1.05-1.39)]. Total KB were associated with worse Exam 5 DS performance [β (95% CI): -0.28 (-0.44,-0.12)]. However, we did not find an association between total KB and a decline in cognitive performance ( Figure ). Conclusion: In a multi-ethnic population free of baseline CVD, elevated KB levels were associated with incident dementia and worse performance on a test of working memory.