Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review

  • Nicolaas I Bohnen, University of Michigan, Ann Arbor
  • ,
  • Alison J Yarnall, Newcastle University
  • ,
  • Rimona S Weil, University College London
  • ,
  • Elena Moro, University Grenoble Alpes, F-38000 Grenoble
  • ,
  • Mark S Moehle, Univ Florida, Florida State University System, University of Florida, Florida Museum Nat Hist
  • ,
  • Per Borghammer
  • Marc-André Bedard, McGill University
  • ,
  • Roger L Albin, University of Michigan, Ann Arbor

In patients with Parkinson's disease, heterogeneous cholinergic system changes can occur in different brain regions. These changes correlate with a range of clinical features, both motor and non-motor, that are refractory to dopaminergic therapy, and can be conceptualised within a systems-level framework in which nodal deficits can produce circuit dysfunctions. The topographies of cholinergic changes overlap with neural circuitries involved in sleep and cognitive, motor, visuo-auditory perceptual, and autonomic functions. Cholinergic deficits within cognition network hubs predict cognitive deficits better than do total brain cholinergic changes. Postural instability and gait difficulties are associated with cholinergic system changes in thalamic, caudate, limbic, neocortical, and cerebellar nodes. Cholinergic system deficits can involve also peripheral organs. Hypercholinergic activity of mesopontine cholinergic neurons in people with isolated rapid eye movement (REM) sleep behaviour disorder, as well as in the hippocampi of cognitively normal patients with Parkinson's disease, suggests early compensation during the prodromal and early stages of Parkinson's disease. Novel pharmacological and neurostimulation approaches could target the cholinergic system to treat motor and non-motor features of Parkinson's disease.

TidsskriftLancet Neurology
Sider (fra-til)381-392
Antal sider12
StatusUdgivet - apr. 2022

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