title: White Matter Damage in the 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-basedin vivotracking of cholinergic pathways together with NbM measurement may become a valuablein vivomarker for evaluating the cholinergic system in cognitive disorders.
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Collaborative Innovation Center for Language Competence, Jiangsu Normal University Xuzhou, China.
authors.forename: Zude
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Psychosomatic Medicine, University of RostockRostock, Germany; German Center for Neurodegenerative DisordersRostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical UniversityBeijing, China; Department of Neurology, Beijing Friendship Hospital, Capital Medical UniversityBeijing, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders; Beijing Key Laboratory of Geriatric Cognitive Disorders; Neurodegenerative Laboratory of Ministry of Education of the People's Republic of ChinaBeijing, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
keywords: cholinergic system; cognitive impairment; magnetic resonance imaging; tractography; vascular cognitive impairment no dementia