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A multicenter longitudinal study of cholinergic subgroups in Parkinson disease

Author

Listed:
  • Nicolaas I. Bohnen

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

  • Stiven Roytman

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Sygrid Zee

    (University of Groningen)

  • Giulia Carli

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Fotini Michalakis

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

  • Austin Luker

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

  • Sofie Slingerland

    (University of Groningen)

  • Kirk A. Frey

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Peter J. H. Scott

    (University of Michigan)

  • Robert A. Koeppe

    (University of Michigan
    University of Michigan)

  • Teus Laar

    (University of Groningen)

  • Roger L. Albin

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Prabesh Kanel

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

Abstract

Parkinson disease (PD) is a heterogeneous syndrome. There is a need for biology-driven subtyping to inform specific therapeutic strategies. In a two-center study with de novo and established PD cohorts, we use vesicular acetylcholine transporter ligand [18F]FEOBV brain PET to assess cholinergic systems changes in early to moderate PD. Principal component analysis (PCA) is applied to data from 245 PD subjects to define cholinergic subgroups at baseline. Three PD subgroups are identified: hypercholinergic (regional upregulation; 29%), mixed (regional upregulation and regional deficits; 40.8%) and hypocholinergic (regional deficits only; 30.2%). Evidence of upregulation is observed in the subcortical-anterior cortical regions, whereas cholinergic downregulation is found in posterior cortical regions. Cholinergic upregulation and downregulation exhibit distinct associations with clinical symptoms. Longitudinal analysis (2-3 year interval) in 128 PD subjects reveals differential progressions by subgroup. This subtyping approach expands understanding of cholinergic progression in PD and may inform identification of new therapeutic targets.

Suggested Citation

  • Nicolaas I. Bohnen & Stiven Roytman & Sygrid Zee & Giulia Carli & Fotini Michalakis & Austin Luker & Sofie Slingerland & Kirk A. Frey & Peter J. H. Scott & Robert A. Koeppe & Teus Laar & Roger L. Albi, 2025. "A multicenter longitudinal study of cholinergic subgroups in Parkinson disease," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60815-0
    DOI: 10.1038/s41467-025-60815-0
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