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.