Heterogeneity in progression of prodromal features in Parkinson's disease

In the pre-diagnostic phase of Parkinson's disease (PD), a range of motor and non-motor symptoms can occur. However, there is considerable variability in their onset and currently little information exists on the pattern of progression of clinical features before diagnosis.

We analysed data from a survey amongst patients with PD from 11 European countries by the European Parkinson's Disease Association. They completed questions on first occurrence of 21 pre-diagnostic features. A principal component analysis (PCA) with varimax rotation was performed to determine the co-occurrence of these features.

1467 patients were included. Changes in movement were the most commonly reported features up to 4 years before diagnosis. However, at five or more years before diagnosis loss of sense of smell, sleep problems, fatigue and other non-motor features had been experienced most frequently. PCA of pre-diagnostic features' duration revealed three factors with eigenvalues over Kaiser's criterion of 1: a) a neuropsychiatric factor comprised of anxiety, depression, apathy, stress, and sleep problems; b) an axial factor defined by difficulty eating and/or swallowing problems, freezing, and falls/balance problems; and c) a motor factor with additional non-motor features. Bladder/bowel problems and tremor had low factor loadings on all components. However, in those with disease duration less than 5 years the autonomic features were associated with the axial factor and tremor loaded on both the motor and psychiatric symptom factors.

The identified symptom complexes in the pre-diagnostic stage of PD may be reflective of a shared pattern of pathological disease progression.