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February 19, 2018

When Do α-Synucleinopathies Start? An Epidemiological TimelineA Review

Author Affiliations
  • 1Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 2Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. Published online February 19, 2018. doi:10.1001/jamaneurol.2017.4243

Importance  This article reviews the epidemiological evidence of features of α-synucleinopathies that precede clinical onset of disease, proposes a clinical timeline, and attempts to define the different premotor and clinical phenotypes associated with α-synucleinopathies.

Observations  The pathological hallmarks of the α-synucleinopathies (Parkinson disease, Parkinson disease dementia, dementia with Lewy bodies, and multisystem atrophy) begin years before a clinical diagnosis. Epidemiologic studies support the long gap between pathology and symptoms and suggest that certain nonmotor conditions (constipation, anxiety, and rapid eye movement sleep behavior disorder) precede the traditional motor Parkinson disease phenotype by long intervals.

Conclusions and Relevance  Characterizing the temporal onset of these conditions will help to better recognize the premotor phase of the α-synucleinopathies and specific clinical phenotypes and will guide the search for predictive biomarkers and risk or protective factors for Parkinson disease and other synucleinopathies.