GLYCEMIC STATES MODULATE CORTICAL THICKNESS AND STRUCTURAL CONNECTIVITY IN OLD AGE

Abstract

Diabetes mellitus (DM) is a common chronic disease and is known to increase risk of cognitive decline and dementia, including AD. The level of glycated hemoglobin (HbA1c) is positively associated with the risk of developing dementia. DM is associated with global gray matter volume loss, though this remains inconsistent across studies. Therefore, this study aims to investigate the associations between glycemic states, gray matter thickness, and white matter structural connectivity in a senior volunteer cohort. Twenty senior volunteers between the age of 60 and 80 were enrolled from local communities in Hualien, Taiwan. Venous blood was drawn from every participant, with glycemic indices including HbA1c, fasting glucose, and fasting insulin. From each participant, we obtained T1-weighted MRI (TR/TE=1.16/0.8 ms; flip angle =15°; matrix size =512x512; slice thickness =1.0 mm; final voxel size of 160.x60.5 mm) and diffusion tensor images (DTI) (3 mm axial slices, 256*256 matrix, 1*1 mm in-plane resolution, 30 directions) using a 3T GE scanner. Gray matter thickness was extracted from T1 scans, and fractional anisotropy (FA) and mean diffusivity (MD) were determined from DTI data. Both T1 and DTI data were co-registered to the MNI152 template. Correlation between these data and each of the glycemic indices was examined in regions previously shown to be susceptible to DM and AD using the Spearman correlation coefficient. Participants had a mean age of 66.5±5.0 years, and were 75% female. After controlling for age and gender, significant correlations were found between insulin with MD (ρ=-0.47, p=0.047) and cortical thickness of parahippocampus (ρ=0.56, p=0.02), HbA1c with MD (ρ=0.51, p=0.03) and cortical thickness of insular (ρ=0.52, p=0.02), and glucose with middle temporal cortical thickness (ρ=-0.49, p=0.04). Gray matter thickness and white matter structural connectivity are significantly correlated with glycemic state, particularly in the posterior regions related to AD and memory capacity. These correlations were strongest for fasting glucose and HbA1c, which may help explain cognitive decline in individuals with DM.