Prabesh Kanel1,2, Marc-André Bedard3,4,5, Meghmik Aghourian3,4,5, Pedro Rosa-Neto4,5, Jean-Paul Soucy4, Roger L Albin6,7,8, Nicolaas I Bohnen9,6,7,8. 1. Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI, 48105-9755, USA. prabeshk@umich.edu. 2. University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA. prabeshk@umich.edu. 3. Cognitive, Pharmacology Research Unit, UQAM, Montreal, Canada. 4. McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada. 5. McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Verdun, Canada. 6. University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI, USA. 7. Department of Neurology, University of Michigan, Ann Arbor, MI, USA. 8. Neurology Service and GRECC, VAAAHS, Ann Arbor, MI, USA. 9. Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI, 48105-9755, USA.
Abstract
PURPOSE OF REVIEW: Brain cholinergic denervation is a major feature of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We reviewed the topography assessed by a cholinergic molecular imaging study in these two major types of dementia. A small meta-analysis directly comparing vesicular acetylcholine transporter (VAChT) PET scans of AD vs. DLB patients is presented. RECENT FINDINGS: VAChT PET studies showed evidence of extensive cortical cholinergic denervation in both forms of dementia, while multiple subcortical structures were also in DLB. Novel analysis revealed evidence of metathalamic denervation in AD, and epithalamus, premotor/sensorimotor cortical, and striatal losses in DLB. Topographically distinct cortical and subcortical cholinergic lesions can distinguish AD and DLB, and new structures have been highlighted here. Differential vulnerability of specific cholinergic projections is likely associated with specific clinical features of these disorders. Improved understanding of the mechanisms and roles of cholinergic neurotransmission in regions with cholinergic deficits may lead to symptomatic therapies.
PURPOSE OF REVIEW: Brain cholinergic denervation is a major feature of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We reviewed the topography assessed by a cholinergic molecular imaging study in these two major types of dementia. A small meta-analysis directly comparing vesicular acetylcholine transporter (VAChT) PET scans of AD vs. DLB patients is presented. RECENT FINDINGS: VAChT PET studies showed evidence of extensive cortical cholinergic denervation in both forms of dementia, while multiple subcortical structures were also in DLB. Novel analysis revealed evidence of metathalamic denervation in AD, and epithalamus, premotor/sensorimotor cortical, and striatal losses in DLB. Topographically distinct cortical and subcortical cholinergic lesions can distinguish AD and DLB, and new structures have been highlighted here. Differential vulnerability of specific cholinergic projections is likely associated with specific clinical features of these disorders. Improved understanding of the mechanisms and roles of cholinergic neurotransmission in regions with cholinergic deficits may lead to symptomatic therapies.
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Authors: Prabesh Kanel; Sygrid van der Zee; Carlos A Sanchez-Catasus; Robert A Koeppe; Peter J H Scott; Teus van Laar; Roger L Albin; Nicolaas I Bohnen Journal: Aging Brain Date: 2022-03-28
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