Mixed-brain pathologies are the most common cause of progressive parkinsonism in older adults. We tested the hypothesis that the impact of individual pathologies associated with progressive parkinsonism, differ among older adults.
Data was from 1089 decedents who had undergone annual clinical testing and autopsy. Parkinsonism was based on a modified United Parkinson’s Disease Rating Scale. Linear mixed-effects models were employed, to investigate the combinations of nine pathologies related to progressive parkinsonism. Then we estimated the person-specific contributions of each pathology for progressive parkinsonism.
The average participant showed three pathologies. Parkinson’s disease (PD) and four cerebrovascular pathologies [macroinfarcts, atherosclerosis, arteriolosclerosis and cerebral amyloid angiopathy (CAA)] but not AD, TDP-43, hippocampal sclerosis and microinfarcts, were independently associated with progressive parkinsonism. These pathologies accounted for 13% of additional variance of progressive parkinsonism. Thirty-one different combinations of these five pathologies were observed to be associated with progressive parkinsonism observed. On average, PD and CAA accounted respectively for 66% and 65% of person-specific progression of parkinsonism, while macroinfarcts, atherosclerosis and arteriolosclerosis accounted for 41%-48%.
There is much greater heterogeneity in the comorbidity and relative impact of individual brain pathologies affecting progressive parkinsonism than previously recognized and this may account in part for its phenotypic heterogeneity in older adults.

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