Association between metabolic profile and cognitive frailty in community-dwelling older adults: An eight-year cohort...

Limited studies have explored the link between metabolic profiles and cognitive frailty, its temporal relationship is especially lacking. This study aimed to identify metabolic patterns associated with cognitive frailty over time. This eight-year prospective cohort study (2011-2019) recruited 605 nondemented community-dwelling older adults at baseline. Cognitive frailty, assessed biennially, was defined as physical frailty and mild cognitive impairment. Baseline plasma metabolites were evaluated using ¹H nuclear magnetic resonance. Generalized linear mixed models assessed the longitudinal association between metabolites and cognitive frailty, further stratified by important covariates. We found that one unit increment of baseline fatty acyl chain (CH₂CH₂CC) Z-score was associated with worsening cognitive frailty at baseline [adjusted risk ratio (aRR)= 1.97], which attenuated over eight years (aRR=0.94). In contrast, one unit increment of baseline pyruvate Z-score was associated with attenuation in the progression to the next stage of cognitive frailty (aRR=0.94). These associations were more evident in men, individuals with > 12 years of education, and apolipoprotein E (APOE) ε4 non-carriers (aRR=0.34-0.92). Significant interactions were found between APOE ε4 status and both fatty acyl chain (P_interaction=0.004) and pyruvate (P_interaction=0.03). Our findings suggest plasma metabolites may serve as markers for predicting cognitive frailty and APOE genotypes modifying this pathogenesis.