The resting perfusion pattern associates with functional decline in type 2 diabetes

Abstract

We investigated the relationships between cerebral blood flow (CBF), cognitive, and mobility decline in type 2 diabetes mellitus (T2DM) over a 2-year period. Seventy-three participants (41 T2DM and 32 controls) were evaluated using volumetric CBF with arterial spin labeling perfusion magnetic resonance imaging at baseline and at the 2-year follow-up. Regions with significant CBF differences between T2DM participants and controls at baseline were detected using voxel-wise analysis. Correlation analysis was performed to investigate the association between regional CBF and cognitive or mobility performance over the 2-year span. Compared to controls, participants with T2DM had decreased CBF in the resting-state default mode, visual, and cerebellum networks. Greater decrease in longitudinal CBF values at these regions over a 2-year span was associated with worse gait, memory and executive functions, and higher baseline insulin resistance and worse baseline cognitive performance. In T2DM, impairment of resting regional perfusion is closely related to worse cognitive and mobility performance. Insulin resistance may further contribute to regional perfusion deficit in T2DM.

Keywords: Arterial spin labeling MRI; Cerebral blood flow; Cognitive impairment; Insulin resistance; Type 2 diabetes mellitus; Voxel-based analyses.

Fig. 1

Compared to controls, T2DM patients exhibited significantly reduced Cerebral Blood Flow (CBF) in (a) a posterior cluster, including occipital, cerebellum, posterior cingulate, precuneus, cuneus, thalamus, basal ganglia regions, and (b) an anterior cluster (pointed by light blue arrows), including the ventromedial, ventrolateral and orbitofrontal regions. Cerebrospinal fluid (CSF) was masked out from the clusters for better visibility. The posterior cluster exhibited (c) large overlap with the visual network (in blue color), cerebellum network (in cyan color), and the posterior part of the default mode network (in green color), while the anterior cluster was close to (but not exactly in) the anterior part of the default mode network (in green color). The overlaps between the clusters (posterior cluster in (a) and anterior cluster in (b)) and the brain networks can be seen through the colored brain networks.

Fig. 2

The regions where Cerebral Blood Flow (CBF) is significantly associated with (a) age, (b) hematocrit, and (c) hypertension is overlaid on the anatomical brain. CSF was masked out from the regions for better visibility. CBF is reduced significantly in the prefrontal regions as people age. Subjects with higher hematocrit showed significantly decreased CBF in very extensive areas covering almost all cerebrum, including all frontal, parietal, occipital and temporal regions. Hypertensive subjects showed significantly increased CBF in the posterior cingulate, anterior cingulate, and prefrontal regions.

Fig. 3

Association of baseline absolute Cerebral Blood Flow (CBF) with (a) Gait Speed Dual-Task (DT) and (b) Verbal Fluency (VF): Animal score at the posterior cluster, and (c) Gait Speed (DT) and (d) VF: Animal score at the anterior cluster after correcting for age, hematocrit, hypertension, and gray matter volume.

Fig. 4

Greater longitudinal decline in Cerebral Blood Flow (CBF) at the two-year follow-up is associated with less Total Recall in HVLT (a) at the posterior cluster, (b) at the anterior cluster, and (c) at the default mode network (DMN).

Fig. 5

Greater longitudinal decline in Cerebral Blood Flow (CBF) after two-year follow-up (a) at the anterior cluster and (b) at the default mode network (DMN) is associated with reduced baseline Hopkins Verbal Learning Test (HVLT): retention.