The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities

Abstract

Objective: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances.

Methods: A total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored.

Results: The analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs.

Conclusion: Our study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.

Keywords: cerebellum; magnetic resonance imaging; resting-state functional connectivity; voxel-based morphometry; white matter hyperintensities.

FIGURE 1

Voxel-based morphometry showing gray matter loss in the cerebellar subregions for patients with White matter hyperintensities (WMHs) in comparison with controls. Areas of significant gray matter loss (red) included the cerebellar subregions right-sided lobule VI [voxel size: 2,106; peak MNI coordinates: x = 22.5, y = –63, and z = –15; Gaussian random field (GRF) for voxel levels at P < 0.001 and cluster at P < 0.05] and left-sided lobule VI (voxel size: 703; peak MNI coordinates: x = –22.5, y = –54, and z = –15; GRF for voxel levels at P < 0.001 and cluster at P < 0.05), for patients with WMHs vs. control subjects.

FIGURE 2

Group comparison of cerebellar atrophy. Volume contrasts within two subregions of the cerebellum across four groups. Post-hoc analysis of the brain regions with significant differences among the four groups. (A) The gray matter volume (GMV) of the right-sided cerebellum lobule VI showing atrophy in WMHs groups. (B) The GMV of the left-sided cerebellum lobule VI showing atrophy in WMHs groups. ^∗∗∗P < 0.001, ^∗∗P < 0.01, and ^∗P < 0.05.

FIGURE 3

Differences of functional connectivity (FC) between groups at the right-sided cerebellum lobule VI—whole brain level. (A) Significant differences were observed between patients with WMHs and healthy controls (HC) in the FC between the right-sided cerebellum lobule VI with the left anterior cingulate gyri (voxel size: 39; peak MNI coordinates: x = –3, y = 33, and z = –6; GRF for voxel levels at P < 0.001 and cluster at P < 0.05). (B) The functional connectivity of the right-sided cerebellum lobule VI with the left anterior cingulate gyri was significantly decreased in patients with WMHs. ^∗∗∗P < 0.001.