How will epidemiology shape our knowledge of the patterns of disease progression in Parkinson’s disease?

Questions about the progression of Parkinson’s disease (PD) encompass the beginning of the disease (with what symptoms does it begin), and the subsequent evolution (in what order and how fast the disease progresses). This paper discusses these issues from three points of view: (1) Recent advances (i.e. what have we recently know), (2) knowledge gaps (i.e. what we know/we don’t know – but should) and (3) bridging knowledge gaps (i.e. how will we know).To understand how PD begins we need to observe individuals from the very beginning of the disease, which means assembling a group of individuals before the onset of any PD-associated symptoms. Cohorts can be established to study the very beginnings of PD that are population-based or, perhaps in the future, that are enriched in risk for PD based on genetic risk factors yet to be determined. After onset PD has a heterogeneous course. A number of studies have attempted to understand which symptoms tend to coexist and also to determine clinical subtypes of PD. The value of this ‘subtyping’ may be to prognosticate, if certain types have relatively slower progression of disease, or to define types of PD that have a different pathogenesis and therefore may be amenable to different treatments. To date, however, they have had a cross-sectional rather than longitudinal focus. To understand patterns of progression we must find ways in which to describe patterns of disease progression. These methods can then be applied to studies of etiology and risk factors for PD. If subtypes have distinct determinants then considering PD as a unitary entity by combining subtypes together in analyses risks missing these associations.