Acta Neuropathologica

, Volume 115, Issue 4, pp 409–415 | Cite as

The progression of pathology in longitudinally followed patients with Parkinson’s disease

  • Glenda Halliday
  • Mariese Hely
  • Wayne Reid
  • John Morris
Original Paper

Abstract

The present study describes the pathological progression of longitudinally followed cases with levodopa-responsive Parkinson’s disease who came to autopsy during the Sydney Multicenter Study of Parkinson’s disease. Standardised clinical and neuropathological assessments over five epochs of time verified three different clinicopathological groups. A group of younger onset patients with a typical long duration clinical course of Parkinson’s disease. This group of cases had Lewy body distributions consistent with the Braak staging of disease. In this group, brainstem Lewy bodies dominate in those surviving to 5 years; by 13 years, 50% of cases have a limbic distribution of Lewy bodies; and by 18 years, all will have at least this pathological phenotype. Approximately 25% of cases had an early malignant, dementia-dominant syndrome and severe neocortical disease consistent with dementia with Lewy bodies. The last group had an older onset, shorter survival, and a more complex disease course with higher Lewy body loads and a higher proportion with additional neuropathologies. These cases with higher loads of Lewy bodies and shorter survivals suggest that widespread Lewy body pathology either occurs at the onset of clinical disease or rapidly infiltrates the brain. In these cases with shorter survivals, there was more plaque pathology, supporting a more aggressive and linked phenotype. Our data suggest that the selection of similar study cohorts by pathology alone would not be able to differentiate the three different phenotypes identified. The data are also not consistent with a unitary concept of the pathogenesis of Lewy body disease.

Keywords

Dementia Disease progression Lewy bodies Longitudinal study Parkinson’s disease 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Glenda Halliday
    • 1
  • Mariese Hely
    • 2
  • Wayne Reid
    • 1
  • John Morris
    • 2
  1. 1.Prince of Wales Medical Research Institute and the University of New South WalesRandwickAustralia
  2. 2.Department of NeurologyWestmead HospitalWestmeadAustralia

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