Association of Glycemic Variability With Imaging Markers of Vascular Burden, β-Amyloid, Brain Atrophy, and Cognitive Impairment
Hyemin Jang, Sungjoo Lee, Sungsik An, Yuhyun Park, Soo-Jong Kim, Bo Kyoung Cheon, Ki‐Hwan Ji, Hee Jin Kim, Duk L. Na, Jun Pyo Kim, Kyunga Kim, Sang Won Seo
Abstract
BACKGROUND AND OBJECTIVE: We aimed to investigate the association between glycemic variability (GV) and neuroimaging markers of white matter hyperintensities (WMH), beta-amyloid (Aβ), brain atrophy, and cognitive impairment. METHODS: allele as covariates. Mediation analyses were used to investigate the mediating effect of WMH and Aβ uptake on the relationship between GV and brain atrophy and cognition. RESULTS: = 0.007). Both WMH and increased Aβ 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 → Aβ → memory; direct effect, -0.182 [-0.338 to -0.026]; indirect effect, -0.067 [-0.119 to -0.015]), respectively. In addition, increased Aβ 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]). DISCUSSION: Our 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.