Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease

Abstract

With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration.

Keywords: MDS diagnostic criteria; disease heterogeneity; gold standard; nonmotor prodrome; redefinition of PD; subtypes.

Figure 1

Simplified model of how the type of cortical pathology and clinical presentation of PDD and DLB might interact. Dementia in DLB/PD is associated with two major pathologies: synucleinopathy (i.e., Parkinson pathology) and neuritic amyloidopathy (i.e., Alzheimer pathology). In PD patients who develop dementia very late in their illness, or not at all (far left), neuritic amyloid deposition is minimal (or absent), and cortical pathology is mainly that of α-Syn deposition. At the other extreme, DLB patients with predominant neuritic amyloid deposition and very minimal α-Syn deposition would usually be diagnosed as AD during life, developing clinical DLB hallmarks late (if at all). Between these two extremes of the spectrum lie the most patients with PD and DLB. This hypothetical spectrum is not meant to be exclusive—other factors may also be important in determining dementia onset (e.g., “top down” vs. “bottom up” α-Syn deposition, degree of vascular pathology, and so on).