P4‐221: White Matter Damage in Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment No Dementia

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.

Effect of cholinergic pathway disruption on cortical and subcortical volumes in subcortical vascular cognitive impairment

“…The extent of WMH within each region was identified using a standard template and quantified as 0, 1 or 2 according to the following scale [0, none; 1, mild (<50% of area); 2, moderate to severe (≥50%)]. Weighted factors (1)(2)(3)(4) were multiplied into each region's score based on the cholinergic tract densities [7].…”

“…These brain regions perform cognitive functions, including processing speed, fluency and working memory [3]. Thus, white matter hyperintensities (WMH) in cholinergic pathways may cause pathologic changes within cortical and subcortical structures innervated by cholinergic neurons and may become a pathological contributor to subcortical vascular cognitive impairment (scVCI) [4].We investigated the association between cholinergic pathway disruption by WMH and volumes of cortical and subcortical brain regions innervated by cholinergic neurons.…”