Temporal sequence of incident mild cognitive impairment, incident parkinsonism, and risk of death in unimpaired community-dwelling older adults.

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Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death. 1,255 community-dwelling unimpaired participants from two epidemiological cohorts were examined annually. MCI was based on neuropsychological testing, and parkinsonism was based on the motor portion of the modified Unified Parkinson's Disease Rating Scale. A multi-state Cox proportional hazards model simultaneously examined incidences of MCI, parkinsonism, and death. Average age at baseline was 76.5 years (SD = 7.2) and 73% were female. Incident MCI occurred almost as commonly as incident parkinsonism, yet compared to no impairment, risk of death was higher for MCI (HR = 1.82, 95%CI=1.34, 2.47), but it was not different for parkinsonism (HR = 1.29; 95%CI = 0.95, 1.75). Risk of death for participants with incident MCI who progressed to parkinsonism (40%) was not significantly different from those with MCI alone (HR = 1.25, 95%CI = 0.93, 1.69). However, risk of death for participants with incident parkinsonism who progressed to MCI (51%) was significantly higher than those who did not progress (HR = 1.67, 95%CI = 1.27, 2.18), indicating that risk of death is highest with incidence of MCI. The varied patterns of sequential occurrence of cognitive and motor impairment and associated risk of death suggests much greater heterogeneity than previously recognized. Further work is needed to determine the biology underlying the temporal evolution of these phenotypes, and if identification of the various subtypes improves risk stratification.