Progression of symptoms in Parkinson's disease

Abstract Whereas the diagnostic criteria for clinical Parkinson's disease (PD) remain centered on the motor syndrome, it is well-known that PD is a multisystemic disorder characterized by a broad spectrum of motor and non-motor features encompassing neuropsychiatric, dysautonomic, and gastrointestinal disturbances. Non-motor disturbances can appear early in the disease course, often preceding the development of classical motor signs. In view of etiological treatments, early diagnosis is needed; accordingly, the concept of prodromal PD has also been introduced. Different clinical PD subtypes based on age at onset (early versus late onset) and baseline motor profile (postural instability or gait difficulty versus tremor-dominant) are probably insufficient to provide a complete prognostic characterization. By combining motor and non-motor features, cluster analysis has been used to provide a better definition of PD subtypes according to their different prognostic profiles. Regardless of PD subtype classifications, prognosis of patients is mainly determined by motor progression and cognitive impairment. Motor progression includes development of motor fluctuations and dyskinesia. Falls also have a greatly negative impact on quality of life. Older age, symmetrical involvement, cognitive impairment, and longer disease duration have been reported as the strongest predictive factors for motor progression. Established prognostic factors for cognitive impairment and dementia include advanced age and more severe parkinsonism, especially with predominant gait involvement. Reduced cerebrospinal fluid Aβ42 levels have consistently been shown to predict the development of cognitive impairment. Genetic factors also influence the risk for developing PD, phenotypic features, and disease course. α-Synuclein gene point mutations and triplications correlate with motor and cognitive impairment. Glucocerebrosidase gene mutations lead to early dementia and psychosis. A better knowledge of prognostic factors in PD will allow physicians to personalize treatment when disease-modifying drugs will be available.