White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia

Qing Liu, Zude Zhu, Stefan J Teipel, Jianwei Yang, Yi Xing, Yi Tang, Jianping Jia, Qing Liu, Zude Zhu, Stefan J Teipel, Jianwei Yang, Yi Xing, Yi Tang, Jianping Jia

Abstract

Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.

Keywords: cholinergic system; cognitive impairment; magnetic resonance imaging; tractography; vascular cognitive impairment no dementia.

Figures

FIGURE 1
FIGURE 1
Seeds for white matter tracking. Yellow for NbM, green for bilateral cingulum (Cing), light blue for external capsule (ExCap) and red for claustrum (Claus).
FIGURE 2
FIGURE 2
Tracked pathways and FA values. (A) 3D Reconstructed pathways (blue) for each division and the ROIs. Yellow for NbM, green for bilateral cingulum, light blue for external capsule and red for claustrum. (B) Overlapped pathways. Yellow for NbM seed, green for the pathway passing through the cingulum, light blue for the pathway passing through the external capsule, and red for the pathway passing through the claustrum. (C) Significantly higher FA values in the Control group compared with the VCIND group in all three cholinergic pathways. Cing, cingulum; ExCap, external capsule; Claus, claustrum. ∗∗∗p < 0.001.

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