Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes

Objective: The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span. Methods: Sixty-five participants (aged 66 ± 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models. Results: After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p < 0.0001-0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r 2 adj 0.35, p 0.04), and lower global vasodilation was associated with a greater decline in executive function (r 2 adj 0.6, p 0.047). Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group (r 2 adj 0.16-0.53, p 0.007-0.048), independent of diabetes control and 24-hour blood pressure. Higher glycated hemoglobin A 1c levels were associated with a greater increase in vasoconstriction in the T2DM group. Conclusions: Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM.