Parkinson's disease: clinical subtyping can help estimate course, survival

  • JAMA Neurol

  • curated by Susan London
  • Clinical Essentials
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  • 3 subtypes of Parkinson's disease evident at diagnosis are associated with disease course and survival.

Why this matters

  • Persistent difficulty in accurately estimating prognosis.

Key results

  • 3 subtypes identified:
    • Mild-motor predominant (48.7% of patients).
    • Intermediate (35.1% of patients).
    • Diffuse malignant (16.2% of patients).
  • Graded associations seen for earlier milestone development, shorter survival.
  • Diffuse malignant subtype independently predicted:
    • Any disease milestone (aHR, 10.90; P<.001>
    • Death (aHR, 3.65; P<.001>
  • Smaller significant elevations of risk also seen for intermediate subtype.
  • Only other variable independently predicting outcomes was age at diagnosis:
    • Any disease milestone (aHR, 1.09; P<.001>
    • Death (aHR, 1.14; P<.001>
  • Subtypes did not differ on staging of Lewy pathology, Alzheimer's disease-related pathology.

Study design

  • UK retrospective cohort study: 111 consecutive patients with autopsy-confirmed Parkinson's disease regularly seen throughout their disease course, having brain autopsy.
  • Subtypes defined on 4 factors at diagnosis: motor symptom severity, rapid eye movement sleep behavior disorder, autonomic function, cognitive function.
  • Main outcomes: time to disease milestones (recurrent falls, wheelchair dependence, dementia, care home placement), survival.
  • Funding: National Institute for Health Research University College London Hospitals Biomedical Research Centre.


  • Variations in patient assessment.
  • Patients predominantly had advanced clinical, pathologic stages.

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