Variation In Recent Onset Parkinson'S Disease: Implications For Pre-Motor Detection

Background: The premotor detection of Parkinson’s disease (PD) is desirable in order to test treatments with neuroprotective potential. The ability to achieve this will be affected by the known substantial variations in PD. Objective: To examine the presence and correlates of 4 key non-motor features of PD thought to predate motor presentation. Methods: Hyposmia (University of Pennsylvania smell identification test < 16th centile), rapid-eye movement sleep disturbance (RBD screening questionnaire >4), depression (Leeds > 6) and constipation (<1 motion daily/laxative use) were recorded in recent onset PD cases in the Tracking Parkinson’s (PRoBaND) study. Results: In 858 PD cases, mean age 67.7 years (SD 9.1), 34.1% female, mean disease duration 1.4 years (SD 0.9), hyposmia was present in 71.3%, RBD in 42.5%, constipation in 33.8% and depression in 20.9%. 0 of 4 features were present in 10.1% of cases, 1/4 in 35.6%, 2/4 in 33.2%, 3/4 in 16.6%, and 4/4 in 4.5%. Motor severity (unified Parkinson’s disease rating scale) increased according to the number of non-motor features, from mean 19.8 (SD 9.8) with 0/4, to 28.4 (SD 10.0) for 4/4 features (Kruskal-Wallis p = 0.001). There was no change in Montreal cognitive assessment according to the number of non-motor features (p = 0.445). Conclusions: The frequency of non-motor features in early PD varies, and correlates with motor severity, but not with cognition. A substantial proportion (45.7%) of recent onset PD cases have only one, or none, of the 4 key non-motor features. Using the presence of multiple non-motor features to screen for very early PD will lack sensitivity.