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

Abstract

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 A1c 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.

Figure 1. Associations between cerebral vasoregulation and decline in cognition

(A and B) Perfusion maps for 2 representative participants using a 3T, 3-dimensional CASL MRI. (A) Participant with T2DM who has lower global vasoreactivity. (B) Participant without T2DM who has higher global vasoreactivity. (C) Lower baseline global vasoreactivity is associated with greater decline in IADL scores, and (D) lower baseline global vasodilation is associated with greater decline in composite executive function T scores after the 2-year follow-up in the T2DM group only. No similar effect was observed for the IADL scores (E) and executive function (F) in the control group. Best fit = red solid line; confidence interval = red dashed lines; mean = blue dashed line. CASL = continuous arterial spin labeling (mL/100 g/min/mm Hg); IADL = Instrumental Activities of Daily Living; T2DM = type 2 diabetes mellitus.

Figure 2. Associations between serum inflammatory markers and cerebral vasoregulation in the T2DM group

(A) Higher baseline HbA_1c is associated with greater increase in global cerebral vasoconstriction after 2-year follow-up, and (B) higher sICAM at baseline is associated with greater decrease in global vasoreactivity. Similar associations can be observed between the cerebral vasoregulations and serum sVCAM (C), cortisol (D), CRP (E), and IL-6 (F). Best fit = red solid line; confidence interval = red dashed lines; mean = blue dashed line. CRP = C-reactive protein; HbA_1c = glycated hemoglobin A_1c; IL-6 = interleukin 6; sICAM = soluble intercellular adhesion molecule; sVCAM = soluble vascular adhesion molecule; T2DM = type 2 diabetes mellitus.

Figure 3. Association between HbA_1c level and decline in the MMSE

Across groups, a higher level of HbA_1c at baseline is associated with a greater decline in MMSE score after the 2-year follow-up, independent of the age, sex, years of education, and baseline MMSE score. Squares = participants with type 2 diabetes mellitus; triangles = control participants. Best fit = red solid line; confidence interval = red dashed lines; mean = blue dashed line. HbA_1c = glycated hemoglobin A_1c; MMSE = Mini-Mental State Examination.