Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation

Abstract

Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control.

Keywords: aerobic exercise; arterial spin labeling (ASL); cardiac rehabilitation; cerebral blood flow (CBF); cerebral vascular reactivity (CVR); coronary artery disease.

FIGURE 1

An illustration of the pipeline for multimodal voxel-wise mass-univariate analysis of variance performed to determine the singular effect of CAD on regional CBF. Step 1 involved SPM voxel-wise between-group comparisons of CBF images across the brain. Significant clusters from this step were converted to binary masks and used in step 2 to improve voxel-wise multimodal analysis and limit type II errors. In step 2, between-group differences in CBF were examined voxel-wise using BPM with GMV images from VBM analysis serving as covariates. Corrections for multiple comparisons using FDR (p < 0.05) was performed at each step. Clusters that remained signified regions where CBF changes drive the observed differences as in Figure 3 and as listed in Table 2. Illustration was overlaid on glass brains from SPM8 (http://www.fil.ion.ucl.ac.uk/spm/).

FIGURE 2

Cerebral blood flow (CBF) and CVR images acquired with pCASL from one subject. The representative CBF (normocapnia; top and hypercapnia; middle) and CVR (bottom) maps demonstrate good gray to white matter contrast in parenchymal CBF and no evidence of intravascular artifacts or signal dropouts. Time courses of P_ETCO₂ and total gray matter CBF show the expected CBF response to capnia. Breathing rate (BR) in breaths per minute (BPM) was maintained at 15 breathes per minute (BPM).

FIGURE 3

Regions of decreased gray matter CBF in CAD patients compared to controls. The top portion of the figure shows clusters (yellow) of decreased gray matter CBF overlaid on the axial slices of the Colin27 brain template (MNI) and on a coronal and sagittal slice of the SPM glass brain. Concomitant decrease in GMV and gray matter CBF are shown in the bottom portion of the figure.

FIGURE 4

Regions of differences in regional CVR compared between CAD patients (N = 22) and controls at baseline (N = 13). Statistical differences between groups at p < 0.05 are signified by ^∗ and error bars indicate standard errors of the mean. R, right; L, left; SFG, superior frontal gyrus; ST, superior temporal gyrus; Ins, insula; PostC, post-central gyrus; MT, middle temporal gyrus; PreC, precentral gyrus; AC, anterior cingulate.

FIGURE 5

Increased CBF and recovery in CAD patients post-CR (N = 17). Clusters of higher CBF in right and left anterior cingulate (AC) are shown in red. Conjunction analysis identified recovery of CBF post-CR in a focal area in the right AC (orange, 5; 29; 3, Talairach coordinates) that overlapped with a region of decreased CBF at baseline (yellow).

FIGURE 6

Magnitude of regional CBF changes in CAD patients. The magnitude of changes in CBF and GMV in CAD patients at baseline and recovery after CR are shown here as a relative change. Regions were derived from results of baseline comparisons between patients and controls (Table 2). Statistical differences at p < 0.05 are signified by ^∗ and error bars indicate standard errors of the mean. See Figure 4 footnote for full name of regions.