When do a-Synucleinopathies start? An epidemiological timeline a review

Rodolfo Savica, Boeve F. Bradley, Michelle M. Mielke

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


IMPORTANCE This article reviews the epidemiological evidence of features of a-synucleinopathies that precede clinical onset of disease, proposes a clinical timeline, and attempts to define the different premotor and clinical phenotypes associated with a-synucleinopathies. OBSERVATIONS The pathological hallmarks of the a-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 a-synucleinopathies and specific clinical phenotypes and will guide the search for predictive biomarkers and risk or protective factors for Parkinson disease and other synucleinopathies.

Original languageEnglish (US)
Pages (from-to)503-509
Number of pages7
JournalJAMA neurology
Issue number4
StatePublished - Apr 2018

ASJC Scopus subject areas

  • Clinical Neurology


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