Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism

Abstract

Background and purpose: Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism.

Materials and methods: Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls.

Results: Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (ρ = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (ρ = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (ρ = -0.51, P = .0003).

Conclusions: In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.

Fig 1.

Comparison of the functional connectivity of the right caudate nucleus between patients with vascular parkinsonism and those with Parkinson disease. Contrast is generated as a 2-tailed t test (scale: t = 0.1–5) with a combination of a voxelwise threshold (uncorrected P < .001) and a cluster-extent threshold (family-wise error rate–corrected P < .05), while controlling for age. Increased functional connectivity of the right caudate nucleus to the perigenual anterior cingulate cortex (MNI coordinates: x = 2, y = 44, z = 2) in axial (A), sagittal (B), and coronal (C) planes is observed. Functional connectivity of the right caudate nucleus to the perigenual anterior cingulate cortex positively correlates with normalized caudate nucleus volumes (D).

Fig 2.

Comparison of the functional connectivity of the right caudate nucleus between patients with vascular parkinsonism and controls. Contrast is generated as a 2-tailed t test (scale: t = 0.1–5) with a combination of a voxelwise threshold (uncorrected P < .001) and a cluster-extent threshold (family-wise error rate–corrected P < .05), while controlling for age. Decreased functional connectivity of the right caudate nucleus to the posterior cingulate cortex (MNI coordinates: x = 2, y = −42, z = 36) in the axial (A), sagittal (B), and coronal (C) planes is observed. Functional connectivity of the right caudate nucleus to the posterior cingulate cortex negatively correlates with the number of errors during the Stroop Task (D).