The cholinergic system and Parkinson disease.

Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE

Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.

Brain Stem/*pathology ; Cholinergic Fibers/*pathology ; Neurodegenerative Diseases/*pathology ; Parkinson Disease/*pathology ; Prosencephalon/*pathology; Biomarkers/metabolism ; Brain Stem/diagnostic imaging ; Cholinergic Fibers/diagnostic imaging ; Cholinergic Fibers/metabolism ; Cholinergic Fibers/physiology ; Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/diagnostic imaging ; Lewy Body Disease/metabolism ; Lewy Body Disease/pathology ; Lewy Body Disease/physiopathology ; Models, Neurological ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/physiopathology ; Parkinson Disease/diagnosis ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/metabolism ; Parkinson Disease/physiopathology ; Positron-Emission Tomography/methods ; Prosencephalon/diagnostic imaging

Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non-motor features. Non-motor comorbidities, such as cognitive impairment, are likely the result of an intricate interplay of multi-system degenerations and neurotransmitter deficiencies extending beyond the loss of dopaminergic nigral neurons. The pathological hallmark of parkinsonian dementia is the presence of extra-nigral Lewy bodies that can be accompanied by other pathologies, such as senile plaques. Lewy first identified the eponymous Lewy body in neurons of the nucleus basalis of Meynert (nbM), the source of cholinergic innervation of the cerebral cortex. Although cholinergic denervation is recognized as a pathological hallmark of Alzheimer disease (AD), in vivo neuroimaging studies reveal loss of cerebral cholinergic markers in parkinsonian dementia similar to or more severe than in prototypical AD. Imaging studies agree with post-mortem evidence suggesting that basal forebrain cholinergic system degeneration appears early in PD and worsens coincident with the appearance of dementia. Early cholinergic denervation in PD without dementia appears to be heterogeneous and may make specific contributions to the PD clinical phenotype. Apart from well-known cognitive and behavioral deficits, central, in particular limbic, cholinergic denervation may be associated with progressive deficits of odor identification in PD. Recent evidence indicates also that subcortical cholinergic denervation, probably due to degeneration of brainstem pedunculopontine nucleus neurons, may relate to the presence of dopamine non-responsive gait and balance impairments, including falls, in PD.
(Published by Elsevier B.V.)

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P01 NS015655 United States NS NINDS NIH HHS; P01 NS015655-26A10018 United States NS NINDS NIH HHS; P01 NS015655-26A19010 United States NS NINDS NIH HHS; R01 NS070856 United States NS NINDS NIH HHS

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Date Created: 20100112 Date Completed: 20110909 Latest Revision: 20231103

20231215

PMC2888997

10.1016/j.bbr.2009.12.048

20060022