Accelerated executive functions decline and gray matter structural changes in middle-aged type 1 diabetes mellitus patients with proliferative retinopathy

Background: The aim of the present study was to determine trajectories of cognitive and cortical changes over time in middle-aged patients with type 1 diabetes mellitus (T1DM) and proliferative retinopathy. Methods: Twenty-five patients and 25 controls underwent neuropsychological assessment and neuroimaging twice in a mean (+/- SD) of 3.56 +/- 0.65 and 3.94 +/- 0.91 years, respectively (P = 0.098). Cognitive assessment included the domains of general cognitive ability, memory, information processing speed, executive functions, attention, and motor and psychomotor speed. Symmetrized percentage change in local cortical thickness, surface area, and volume was determined using the FreeSurfer 6 vertex-wise general linear model method. Analyses were performed uncorrected and corrected for baseline systolic blood pressure and depressive symptoms. Results: In patients versus controls, accelerated executive function decline was accompanied by, but not related to, lower left frontal and temporal surface area, left parietal and right frontal thickness, and bilateral frontal and right posterior cingulate volume (family-wise error [FWE]-corrected P < 0.05 for all). In patients, lower executive performance was related to loss of right precuneus surface area (P-FWE = 0.005). Higher HbA1c during follow-up was related to executive function decline (r = -0.509, P = 0.016) and loss of left hemisphere surface area (r(corrected analysis) = -0.555, P = 0.007). Conclusions: After 3.5 years of follow-up, middle-aged T1DM patients with proliferative retinopathy, mild focal changes in executive functions, and cortical structure were found, which may indicate accelerated aging.