Variability in Cardiometabolic and Inflammatory Parameters and Cognitive Decline

Introduction: The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. This study investigates the association of visit-to-visit variability in BMI, mean arterial pressure, total cholesterol, triglycerides, HbA1c, high-sensitivity Creactive protein, ferritin, and fibrinogen with cognitive decline. Methods: This population-based cohort study included 2,260 individuals (mean age=63.0 [SD=7.5] years) free of cognitive diseases who underwent >= 3 clinical measurements from 2004 to 2019. Variability was expressed as variability independent of the mean across visits. Participants were divided on the basis of quartiles of variability score, a scoring system generated to explore the composite effect of parameter variability (range=0-24), where 0 points were assigned for Quartile 1, 1 point was assigned for Quartile 2, 2 points were assigned for Quartile 3, and 3 points were assigned for Quartile 4, each for the variability of 8 parameters measured as variability independent of the mean. Linear mixed models evaluated the longitudinal associations with cognitive decline in memory and verbal fluency. All analyses were conducted in 2020-2021. Results: Higher BMI, mean arterial pressure, total cholesterol, HbA1c, and ferritin variability were linearly associated with cognitive decline irrespective of their mean values. In addition, participants in the highest quartile of variability score had a significantly worse cognitive decline rate in memory (-0.0224 points/year, 95% CI= -0.0319, -0.0129) and verbal fluency (-0.0088 points/year, 95% CI= -0.0168, -0.0008) than those in the lowest quartile. Conclusions: A higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline. Stabilizing these parameters may serve as a target to preserve cognitive functioning.