Association of Glycemic Variability With Imaging Markers of Vascular Burden, β-Amyloid, Brain Atrophy, and Cognitive Impairment

초록

Background and ObjectiveWe aimed to investigate the association between glycemic variability (GV) and neuroimaging markers of white matter hyperintensities (WMH), beta-amyloid (A beta), brain atrophy, and cognitive impairment.MethodsThis was a retrospective cohort study that included participants without dementia from a memory clinic. They all had A beta PET, brain MRI, and standardized neuropsychological tests and had fasting glucose (FG) levels tested more than twice during the study period. We defined GV as the intraindividual visit-to-visit variability in FG levels. Multivariable linear regression and logistic regression were used to identify whether GV was associated with the presence of severe WMH and A beta uptake with DM, mean FG levels, age, sex, hypertension, and presence of APOE4 allele as covariates. Mediation analyses were used to investigate the mediating effect of WMH and A beta uptake on the relationship between GV and brain atrophy and cognition.ResultsAmong the 688 participants, the mean age was 72.2 years, and the proportion of female participants was 51.9%. Increase in GV was predictive of the presence of severe WMH (coefficient [95% CI] 1.032 [1.012-1.054]; p = 0.002) and increased A beta uptake (1.005 [1.001-1.008]; p = 0.007). Both WMH and increased A beta uptake partially mediated the relationship between GV and frontal-executive dysfunction (GV -> WMH -> frontal-executive; direct effect, -0.319 [-0.557 to -0.080]; indirect effect, -0.050 [-0.091 to -0.008]) and memory dysfunction (GV -> A beta -> memory; direct effect, -0.182 [-0.338 to -0.026]; indirect effect, -0.067 [-0.119 to -0.015]), respectively. In addition, increased A beta uptake completely mediated the relationship between GV and hippocampal volume (indirect effect, -1.091 [-2.078 to -0.103]) and partially mediated the relationship between GV and parietal thickness (direct effect, -0.00101 [-0.00185 to -0.00016]; indirect effect, -0.00016 [-0.00032 to -0.000002]).DiscussionOur findings suggest that increased GV is related to vascular and Alzheimer risk factors and neurodegenerative markers, which in turn leads to subsequent cognitive impairment. Furthermore, GV can be considered a potentially modifiable risk factor for dementia prevention.

키워드