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When Do α-Synucleinopathies Start? An Epidemiological Timeline: A Review.
Rodolfo Savica1,2, Bradley F Boeve1, Michelle M Mielke1,2
1Department of Neurology, Mayo Clinic, Rochester, Minnesota.
JAMA Neurology
|February 21, 2018
Summary
Features of alpha-synucleinopathies, such as constipation and sleep disorders, appear years before Parkinson disease symptoms. Recognizing these premotor signs aids early diagnosis and biomarker research.
Area of Science:
- Neurology
- Epidemiology
- Pathology
Background:
- Alpha-synucleinopathies, including Parkinson disease, exhibit pathological changes years before clinical diagnosis.
- Epidemiologic studies reveal a significant gap between disease pathology and symptom manifestation.
Purpose of the Study:
- To review epidemiological evidence of pre-clinical alpha-synucleinopathy features.
- To propose a clinical timeline for alpha-synucleinopathies.
- To define premotor and clinical phenotypes of alpha-synucleinopathies.
Main Methods:
- Review of epidemiological evidence.
- Analysis of clinical timelines.
- Phenotypic characterization of alpha-synucleinopathies.
Main Results:
- Non-motor symptoms like constipation, anxiety, and REM sleep behavior disorder precede motor symptoms of Parkinson disease by long intervals.
- Pathological hallmarks of alpha-synucleinopathies manifest years prior to clinical diagnosis.
Conclusions:
- Characterizing the temporal onset of pre-clinical conditions improves recognition of the premotor phase.
- Identifying these early signs aids biomarker discovery and understanding risk factors for Parkinson disease and other synucleinopathies.
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