02769nas a2200229   4500008004100000022001400041245013000055210006900185260001600254520199500270100002802265700002602293700002302319700002002342700002502362700002502387700002002412700002202432700002502454700002402479856003602503       2024                        eng d  a2152-525000aCirculating Ketone Bodies, Pyruvate, and Citrate and Risk of Cognitive Decline, Structural Brain Abnormalities, and Dementia.0 aCirculating Ketone Bodies Pyruvate and Citrate and Risk of Cogni  c2024 Nov 083 a<p>The relationship between key energy metabolites and brain health is not well understood. We investigated the association between circulating ketone bodies, pyruvate, and citrate with cognitive decline, structural brain characteristics, and risk of dementia. We measured ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone), pyruvate, and citrate species using NMR in plasma samples from 1,850 older adults in the Cardiovascular Health Study collected in 1989-90 or 1992-93. Cognitive decline was assessed using the modified Mini-Mental State Examination and the Digit Symbol Substitution Test. Dementia was adjudicated by a committee of experts through comprehensive evaluations including cognitive tests, medical records, and interviews with the next of kin. Dementia-related mortality was confirmed by a committee using death certificates and other clinical data from hospitalization. Multivariable linear mixed models were used to assess 9-year cognitive decline, while multivariable Cox regression models evaluated 6-year dementia incidence and 22-year dementia-related mortality. White matter lesions and ventricular size were measured using MRI in 1992-94 and were analyzed using multivariable linear regression models. Higher plasma levels of ketones, particularly β-hydroxybutyrate, were associated with faster cognitive decline (β, -0.10; 95% CI, -0.15 to -0.05; P&;lt.001) and dementia-related mortality (HR per SD, 1.29; 95% CI, 1.07 to 1.56; P=0.023). Higher pyruvate concentrations were associated with slower cognitive decline, smaller ventricular size, lower dementia risk (HR per SD, 0.87; 95% CI, 0.77 to 0.97; P=0.013; P=0.073), and lower dementia mortality. Higher citrate levels were associated with less cognitive decline and lower dementia risk. In adults aged 65 years and older, circulating ketone bodies are associated with faster cognitive decline and higher dementia mortality, while pyruvate and citrate are associated with lower dementia risk.</p>1 aGutierrez-Tordera, Laia1 aMoseholm, Kristine, F1 aTrius-Soler, Marta1 aBulló, Mònica1 aFitzpatrick, Annette1 aConnelly, Margery, A1 aLopez, Oscar, L1 aJensen, Majken, K1 aGuasch-Ferré, Marta1 aMukamal, Kenneth, J  uhttps://chs-nhlbi.org/node/9850