Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs

• Published in: The journal of neuropsychiatry and clinical neurosciences Vol. 32; no. 4; pp. 370 - 375
• Main Authors: Kanel, Prabesh, Müller, Martijn L T M, van der Zee, Sygrid, Sanchez-Catasus, Carlos A, Koeppe, Robert A, Frey, Kirk A, Bohnen, Nicolaas I
• Format: Journal Article
• Language: English
• Published: United States 2020
• Subjects: Acetylcholine - metabolism; Aged; Aged, 80 and over; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Cross-Sectional Studies; Female; Fornix, Brain - diagnostic imaging; Fornix, Brain - metabolism; Fornix, Brain - physiopathology; Humans; Lewy Body Disease - diagnostic imaging; Lewy Body Disease - metabolism; Lewy Body Disease - physiopathology; Male; Nerve Net - diagnostic imaging; Nerve Net - metabolism; Nerve Net - physiopathology; Piperidines; Positron-Emission Tomography; Thalamus - diagnostic imaging; Thalamus - metabolism; Thalamus - physiopathology; Dementia With Lewy Bodies; Neurology; Cognition; Saliency; Dementia
• ISSN: 0895-0172; 1545-7222
• DOI: 10.1176/appi.neuropsych.19070165

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) [ F]-fluoroethoxybenzovesamicol ([ F]-FEOBV) radioligand. 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 [ F]-FEOBV PET. 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. 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.