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

Objective: To examine if indices of Parkinson’s 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 United Parkinson’s Disease Rating Scale and a clinical diagnosis of PD was based on medical history. We employed 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 eight other brain pathologies with the progression of parkinsonism prior to death. Results: During an average of 8.5 years follow-up, more than half (771/1430, 53.9%) developed parkinsonism proximate to death. On average, parkinsonism was progressive (Estimate, 0.130, S.E., 0.005, p<0.001) in all older adults, but more rapid in adults with a clinical diagnosis of PD [N=52; 3...