Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity

Abstract

Objective: The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation.

Research design and methods: CBF was examined in 26 diabetic (aged 61.6 +/- 6.6 years) and 25 control (aged 60.4 +/- 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla.

Results: The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (-13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (-3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region.

Conclusions: Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.

Figure 1

A: Brain regions partitioning method. The first column on the left presents an original axial slice at the level of the ventricles for the IR-FGE (I1), the FLAIR image (F1), and for the CASL acquisition (T2 reference image, C1). The second column illustrates the six regions computed on the images showed on column 1: the left (L) and right (R) side of the frontal (F), parieto-occipital (PO), and temporal (T) regions (as indicated on I2). The last two columns illustrate the processing/reconstruction performed on the images shown in column 1 and the assessment of spatial distribution for the computed parameters. The regions were applied to the segmented IR-FGE image (I3) to assess the regional distribution of gray matter, white matter, and CSF volumes (I4) to the segmented FLAIR image (F3) to assess WMH volume distribution (F4). After reconstruction of the (CBF) maps (an example CO₂ rebreathing map is shown on C3), CBF values were averaged over each region (C4), allowing CO₂ reactivity computation for each region. White matter (B), gray matter (C), CSF (D), and WMH (E) volumes in the frontal (F), temporal (T), parieto-occipital (PO), and cortical (C) regions for both groups, normalized for region volume in control and diabetic (DM) groups (means ± SE). †Between-region comparisons for both groups (P < 0.0001). ‡Between-hemisphere comparisons for both groups (P = 0.004). #Between-group comparisons over all regions (P ≤ 0.006). ***Between-group comparisons within regions (P ≤ 0.0008). *P = 0.04; **P = 0.01.

Figure 2

CBF maps reconstructed from the CASL acquisition for a control subject (A–D) and a diabetic (DM) subject (E–G). A and E: An axial slice of a T2 reference image at the level of the ventricles used for the CBF map reconstruction. B and F: CBF maps at baseline. C and G: CO₂ rebreathing. D and H: Hyperventilation. The perfusion ranges from 0 to 125 ml · 100 g⁻¹ · min⁻¹ on all CBF maps. CBF during the first baseline, the CO₂ rebreathing, and hyperventilation periods (I) and the calculated CO₂ reactivity (J) in the frontal (F), temporal (T), parieto-occipital (PO), and cortical (C) regions in control (□) and diabetic (DM;▪) groups (means ± SE). ††Between-region comparisons for both groups (P < 0.0001). †P = 0.001 ≤ P ≤ 0.006. ##Between-group comparisons over all regions (P = 0.001). #P = 0.005 ≤ P ≤ 0.006.