Progressive parkinsonism in older adults is related to the burden of mixed brain pathologies

Neurology. 2019 Apr 16;92(16):e1821-e1830. doi: 10.1212/WNL.0000000000007315. Epub 2019 Mar 20.

Abstract

Objective: To examine whether indices of Parkinson disease (PD) pathology and other brain pathologies are associated with the progression of parkinsonism in older adults.

Methods: We used data from decedents who had undergone annual clinical testing prior to death and structured brain autopsy. Parkinsonism was based on assessment with a modified Unified Parkinson's Disease Rating Scale and a clinical diagnosis of PD was based on medical history. We used a series of mixed-effects models controlling for age and sex to investigate the association of PD pathology (nigral neuronal loss and Lewy bodies) and indices of 8 other brain pathologies with the progression of parkinsonism prior to death.

Results: During an average of 8.5 years' follow-up, more than half (771/1,430, 53.9%) developed parkinsonism proximate to death. On average, parkinsonism was progressive (estimate 0.130, SE 0.005, p < 0.001) in all older adults, but more rapid in adults with a clinical diagnosis of PD (n = 52; 3.6%) (estimate 0.066, SE 0.021, p < 0.001). Progression of parkinsonism was more rapid in adults with PD pathology (estimate 0.087, SE 0.013, p < 0.001). Alzheimer disease and several cerebrovascular pathologies were all independently associated with more rapid progression (all p values <0.05). The association between a higher person-specific weighted pathology score and more rapidly progressive parkinsonism did not differ between individuals with and without a clinical diagnosis of PD (estimate 0.003, SE 0.047, p = 0.957).

Conclusion: The rate of progressive parkinsonism in older adults with and without a clinical diagnosis of PD is related to the burden of mixed brain pathologies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Brain / pathology*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Parkinsonian Disorders / epidemiology
  • Parkinsonian Disorders / pathology*
  • Prospective Studies
  • Severity of Illness Index