Functional decline in Parkinson disease

Objectives: To determine the overall rate of functional decline and to asse ss the progression of different signs of Parkinson disease (PD). Patients and Methods: Patients with clinically diagnosed PD followed up for at least 3 years were included in this study. Demographic and clinical dat a (including the Unified Parkinson's Disease Rating Scale [UPDRS]) were ana lyzed by the multivariate unbalanced repeated-measurements design using the mixed-effects model to study the association between different symptoms an d various demographic variables. Regression models helped estimate the rate s of progression of the disease in relationship to the various components o f the UPDRS. Patients were categorized as having tremor-dominant or postura l instability-gait difficulty-dominant PD and the 2 categories were compare d for progression of their total UPDRS scores. Design: A multivariate mixed-effects model was used to study the relationsh ip between the different symptoms and various demographic variables. Nonpar ametric statistical tests were used to compare the progression of symptoms in the "on" (good function) state and the "off" (poor function) state group s for 2 age-at-onset categories (less than or equal to 57 and > 57 years). Results: Data from 1731 visits on 297 patients (181 men) followed up for an average of 6.36 years (range, 3-17 years) were analyzed. The annual rate o f decline in the total UPDRS scores was 1.34 when assessed during the on st ate and 1.58 when assessed during the off state. Patients with an older age at onset had more rapid progression of PD than those with a younger age at onset. Furthermore, the older-onset group had statistically significantly more progression in mentation, freezing, and parts I (mentation) and II (ac tivities of daily living) UPDRS subscores. Handwriting was the only compone nt of the UPDRS score that did not notably deteriorate during the observati on period. Regression analysis of 108 patients whose symptoms were rated du ring their off state showed a faster rate of cognitive decline as age at on set increased. The slopes (ie, the annual rates of decline) of progression in the UPDRS scores, when adjusted for age at the initial visit, were steep er for the postural instability-gait-difficulty-dominant group compared wit h the tremor-dominant group. Conclusion: Based on longitudinal follow-up data, our findings provide evid ence for a variable course of progression of the different PD symptoms, thu s implying different biochemical or degenerative mechanisms for the various clinical features associated with PD.