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Published on: July 31, 2019
Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs
Prabesh Kanel1, Martijn L T M Müller1, Sygrid van der Zee1
1Department of Radiology (Kanel, Müller, Sanchez-Catasus, Koeppe, Frey, Bohnen) and Department of Neurology (Frey, Bohnen), University of Michigan, Ann Arbor; Neurology Service and Geriatric Research Education and Clinical Center, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Mich. (Bohnen); Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor (Kanel, Müller, Sanchez-Catasus, Bohnen); and Department of Neurology, University of Groningen, University Medical Center Groningen, the Netherlands (van der Zee).
Objectives:
The authors investigated the topography of cholinergic vulnerability in patients with dementia with Lewy bodies (DLB) using positron emission tomography (PET) imaging with the vesicular acetylcholine transporter (VAChT) [18F]-fluoroethoxybenzovesamicol ([18F]-FEOBV) radioligand.
Methods:
Five elderly participants with DLB (mean age, 77.8 years [SD=4.2]) and 21 elderly healthy control subjects (mean age, 73.62 years [SD=8.37]) underwent clinical assessment and [18F]-FEOBV PET.
Results:
Compared with the healthy control group, reduced VAChT binding in patients with DLB demonstrated nondiffuse regionally distinct and prominent reductions in bilateral opercula and anterior cingulate to mid-cingulate cortices, bilateral insula, right (more than left) lateral geniculate nuclei, pulvinar, right proximal optic radiation, bilateral anterior and superior thalami, and posterior hippocampal fimbria and fornices.
Conclusions:
The topography of cholinergic vulnerability in DLB comprises key neural hubs involved in tonic alertness (cingulo-opercular), saliency (insula), visual attention (visual thalamus), and spatial navigation (fimbria/fornix) networks. The distinct denervation pattern suggests an important cholinergic role in specific clinical disease-defining features, such as cognitive fluctuations, visuoperceptual abnormalities causing visual hallucinations, visuospatial changes, and loss of balance caused by DLB.
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