Background
The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. We aimed to investigate the association of visit-to-visit variability (VVV) in body mass index (BMI), waist-to-height ratio (WHtR), systolic blood pressure (SBP), total cholesterol (TC), triglycerides, glycated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), ferritin, as well as the composite effect of the VVV in these parameters on cognitive decline.
Methods
We performed a longitudinal study using data from adults aged 50 years and older in the English Longitudinal Study of Ageing (ELSA). Biomarkers were assessed at waves 2 (baseline, 2004/2005), 4 (2008/2009), 6 (2012/2013), 8 (2014-2016) and 9 (2018/2019). Cognitive function, including memory, executive function and orientation, were measured. VVV was expressed as the coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) across visits conducted at a mean interval of 3.5 years. To explore the composite effect of parameter variability, we generated a variability score (range: 0-24), where 0 points were assigned for Q1, 1 point for Q2, 2 points for Q3, and 3 points for Q4 each for the variability of eight parameters measured as VIM. Participants were divided based on quartiles of variability score. Linear mixed models were used to evaluate longitudinal associations.
Results
A total of 2366 participants (56.1% women, mean age 63.0 ± 7.5 years) with at least three measurements of biomarkers were included, and the mean follow-up duration was 11.2 ± 2.0 years. Higher BMI, SBP, TC, HbA1c and ferritin variability was linearly associated with global and domain-specific cognitive decline irrespective of their mean values over time. Additionally, compared with the lowest quartile, participants in the highest quartile of variability score had a significantly worse global cognitive decline rate (-0.0238, 95% CI -0.0376, -0.0100), memory decline rate (-0.0224, 95% CI -0.0319, -0.0129) and orientation decline rate (-0.0129, 95% CI -0.0245, -0.0012).
Conclusions
Higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline, and the composite effect of these parameters was evident. Stabilizing these parameters may serve as a target to preserve cognitive function.