Premotor Parkinson’s disease: Concepts and definitions
Open accessAbstract
Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2‐step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high‐risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large‐scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease‐modifying therapy even before the development of evidence of dopamine deficiency. © 2012 Movement Disorder Society
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Lack of dopamine is understood to be the primary cause of many of the movement disorders in Parkinson's disease.
“This lack of dopamine is understood to be the primary cause of many of the movement disorders [127,128].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [128]
The section on the timing of PD screening (page unavailable) links striatal dopamine deficits with clinical motor features of Parkinson’s disease. It does not say that dopamine deficiency is the primary cause of many movement disorders, so the causal emphasis goes beyond what this paper states. (LLM, conf=0.79)
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Benamer, H. T. S., Patterson, J., Wyper, D. J., Hadley, D. M., Macphee, G. J. A., & Grosset, D. G. (2000) · Movement Disorders · doi:10.1002/1531-8257(200007)15:4
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2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951 · see citing works
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Inflammatory bowel diseases and Parkinson's disease
Brudek, T. (2019) · Journal of Parkinson’s Disease · doi:10.3233/jpd-191729 · Cited by 139 · see citing works
Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments
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Danna, R., Kondle, S., Amar, O., Mabourakh, M., Chen, G., Fadol, W. B., & Mohieldin, A. M. (2025) · Biology · doi:10.3390/biology14121787 · Cited by 2 · see citing works
“This lack of dopamine is understood to be the primary cause of many of the movement disorders [127,128].”
- Authors
- Siderowf, A., & Lang, A. E.
- Affiliations
- University of Pennsylvania (US)
- University of Toronto (CA)
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2012-04-15
- Volume
- 27
- Issue
- 5
- Pages
- 608-616
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC3335740
- OpenAlex
- W2077529299
- Cited by
- 174
- References
- 90
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 15 · 2022: 13 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 11 · 2016: 12 · 2015: 21 · 2014: 19 · 2013: 24 · 2012: 6
- FWCI
- 14.64
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS053488, P50NS053488)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, prodromal Parkinson's disease, preclinical detection, dopamine transporter imaging, olfactory testing, Braak staging, substantia nigra pars compacta, LRRK2 mutations, biomarkers, disease-modifying therapy, non-motor symptoms
- MeSH terms
- Humans, Motor Neurons, Parkinson Disease, Early Diagnosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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