Molecular Imaging of the Cholinergic System in Alzheimer and Lewy Body Dementias: Expanding Views

Curr Neurol Neurosci Rep. 2021 Sep 20;21(10):52. doi: 10.1007/s11910-021-01140-z.

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.

Keywords: Acetylcholine; Alzheimer’s disease; Cholinergic imaging; Dementia with Lewy bodies; Epithalamus; Metathalamus.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Brain
  • Cholinergic Agents
  • Humans
  • Lewy Body Disease* / diagnostic imaging
  • Molecular Imaging

Substances

  • Cholinergic Agents