Disturbed neurovascular coupling in patients with white matter hyperintensities: potential biomarker for cognitive impairment

Abstract

Purpose: To explore the neurovascular mechanisms of white matter hyperintensities (WMHs)-related cognitive impairment by introducing a neurovascular biomarker, neurovascular coupling (NVC).

Methods: We applied resting-state functional magnetic resonance imaging combined with arterial spin labeling to investigate the NVC dysfunctional patterns in patients with pure WMHs. Partial correlation, mediation, and exploratory subgroup analyses were adopted to explore the relationship among WMHs, NVC dysfunction, and cognitive decline.

Results: We found 21 brain regions with NVC dysfunction in patients with pure WMHs, mainly distributed in the default mode network, dorsal attention network, subcortical nucleus, and limbic system (p < 0.0125, Bonferroni correction). The NVC dysfunction of brain regions in the subcortical nucleus and limbic system correlated with the total WMHs burden and paraventricular WMHs burden (q < 0.05, FDR correction). The reduced NVC of the left amygdala partially mediated the impact of paraventricular WMHs on executive function (Mediation effect: -0.117; 95%CI: -4.042,-0.011; p < 0.05). Among the WMHs subjects without cognitive impairment, the increased NVC of the left basal ganglia significantly correlated with the MoCA score (r = 0.539, p < 0.05).

Conclusion: These findings reveal an underlying neurovascular mechanism of WMHs-related cognitive impairment. The neurovascular functions of the left amygdala and left basal ganglia may involve cognitive damage and compensation, respectively, and can be used as potential biomarkers and therapeutic targets for cognitive impairment in patients with WMHs.

Keywords: Arterial spin labeling; Cognitive impairment; Functional magnetic resonance imaging; Neurovascular coupling; White matter hyperintensities.