Clinical Manifestations.

Abstract

Type 2 diabetes (T2DM) is recognised as a major contributor to cognitive decline. People with T2DM demonstrate abnormalities on MRI compared to control individuals. The aim of this analysis was to investigate differences in cognitive performance and brain volume between individuals with T2DM participating in the Diabetes-and-Dementia (D2) study and a group of healthy controls (HC) part of the Cognition And Neocortical Volume After Stroke (CANVAS) study. One hundred and fifty individuals with T2DM and 36 cognitively-normal participants completed neuropsychological assessments and a 3T-MRI scan. FreeSurfer was used to estimate total brain volume (TBV), mean cortical thickness and subcortical volumes, including the thalami and caudate nuclei. Averages between left and right volumes were calculated for subcortical structures. WMH volumes were estimated manually using FLAIR MRI. Five cognitive domains, including attention, visuospatial skills, memory, language and executive function were computed using z-scores. These domains were used to compare cognitive performance between individuals with and without T2DM. Demographic and clinical comparisons were completed in MATLAB using Two-Sample t-test (age), Fisher Exact test (education, sex, APOE-e4), and Wilcoxon Rank Sum test (BMI). A linear regression model was used to compare cognitive performance between the two groups with correction for age, sex and education level (more/less than 12 years), as well as total intracranial volume for comparing brain volumes. Participants with T2DM were significantly younger, with a higher BMI, had reduced cortical thickness, significantly smaller TBV and smaller subcortical volumes including thalamic, brainstem, amygdala, accumbens area and choroid plexus. Individuals with T2DM exhibited a poorer cognitive performance on tests of language, memory, attention, and visuospatial skills compared to the HC group. There were no significant differences between the two groups in terms of sex, education level, APOE-e4 carriage, WMH, hippocampal volume (see Table 1). T2DM is associated with accelerated structural brain aging, manifesting as cerebral atrophy and poorer cognitive function.