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Published Online: 5 June 2020

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

Prabesh Kanel, Ph.D. [email protected], Martijn L.T.M. Müller, Ph.D., Sygrid van der Zee, M.S., Carlos A. Sanchez-Catasus, Ph.D., Robert A. Koeppe, Ph.D., Kirk A. Frey, M.D., Ph.D., and Nicolaas I. Bohnen, M.D., Ph.D.Authors Info & Affiliations
Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
Volume 32, Number 4
https://doi.org/10.1176/appi.neuropsych.19070165
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Abstract

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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Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Volume 32 • Number 4 • Fall 2020
Pages: 370 - 375
PubMed: 32498602

History

Received: 22 July 2019
Revision received: 13 December 2019
Accepted: 20 March 2020
Published online: 5 June 2020
Published in print: Fall 2020

Keywords

  1. Dementia
  2. Neurology
  3. Cognition
  4. Dementia With Lewy Bodies
  5. Saliency

Authors

Affiliations

Prabesh Kanel, Ph.D. [email protected]
Department 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).
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Martijn L.T.M. Müller, Ph.D.
Department 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).
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Sygrid van der Zee, M.S.
Department 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).
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Carlos A. Sanchez-Catasus, Ph.D.
Department 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).
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Robert A. Koeppe, Ph.D.
Department 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).
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Kirk A. Frey, M.D., Ph.D.
Department 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).
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Nicolaas I. Bohnen, M.D., Ph.D.
Department 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).
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Notes

Send correspondence to Dr. Kanel ([email protected]).

Competing Interests

Dr. Müller has received research support from the Department of Veterans Affairs, the Michael J. Fox Foundation, and NIH. Dr. Koeppe has received grant support from NIH. Dr. Frey has received research support from AVID Radiopharmaceuticals (Eli Lilly subsidiary), GE Healthcare, and NIH; he has served as a consultant to AVID Radiopharmaceuticals, Bayer-Schering, GE Healthcare, and MIMVista; and he is a shareholder with Bristol-Myers, GE Healthcare, Merck, and Novo-Nordisk. Dr. Bohnen has received research support from the Department of Veterans Affairs, EIP Pharma, Eisai, the Michael J. Fox Foundation, and NIH. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by NIH (grants P01 NS015655, RO1 NS070856, and P50 NS091856).

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