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Cited by 42Parkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment ResearchNeurological disorders and treatments

Onset of Skin, Gut, and Genitourinary Prodromal Parkinson's Disease: A Study of 1.5 Million Veterans

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Scott, Gregory D., Lim, Miranda M., Drake, Matthew G., Woltjer, Randy, Quinn, Joseph F.·2021·Movement Disorders
DOI 10.1002/mds.28636PMC PMC8734457
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Abstract

Background: Prodromal Parkinson's disease of skin, genitourinary, and gastrointestinal systems offers a unique window for understanding early disease pathogenesis and developing disease modifying treatments. However, prior studies are limited by incomplete timing information, small sample size, and lack of adjustment for known confounders. Verifying prodromal timing and identifying new disorders in these accessible organs is critically important given their broad use. Objective: We aimed to measure onset timing for gastrointestinal, genitourinary, and skin disorders in a large, nationwide clinically characterized cohort of 1.5 million participants. Methods: Patients with Parkinson's disease (n = 303,693) were identified using diagnostic codes in the medical records database of the United States Veterans Affairs healthcare system and were compared 4:1 with matched controls. Disorder prevalence and estimated onset times were assessed for 20 years preceding diagnosis. Results: The earliest significantly increased prodromal disorders were gastroesophageal reflux, sexual dysfunction, and esophageal dyskinesia at 17, 16, and 15 years before diagnosis. Estimated onset times for each disorder occurred 5.5 ± 3.4 years before the first measured increase. The earliest estimated onset times were smell/taste, upper gastrointestinal tract, and sexual dysfunction at 20.9, 20.6, and 20.1 years before diagnosis. Onset times for constipation and urinary dysfunction were notably longer by 7 and 9 years compared to prior studies in sleep disorder patients. Dermatophytosis and prostatic hypertrophy were identified as new high prevalence prodromal disorders. Conclusions: Gastrointestinal, genitourinary, and skin disorders manifest decades before diagnosis of Parkinson's disease, reiterating their potential as sites for developing early diagnostic testing and understanding pathogenesis.

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  • Non-motor symptoms such as constipation and bloating are among the earliest seen in prodromal PD.

    “First, non-motor symptoms such as constipation and bloating are among the earliest seen in prodromal PD [10, 11].”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [10]

    The Results section, “Estimated Onset Times for Gastrointestinal, Genitourinary, and Skin Disorders” (page unavailable), places constipation early in prodromal PD, with an estimated onset 17.3 years before diagnosis. It does not identify bloating, and it places constipation later than the earliest-onset disorders. (LLM, conf=0.86)

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Authors
Scott, G. D., Lim, M. M., Drake, M. G., Woltjer, R., & Quinn, J. F.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Scott, Gregory D.
ORCID
Venue
Movement Disorders
Publisher
Wiley
Published
2021-05-03
Volume
36
Issue
9
Pages
2094-2103
ISSN
  • 0885-3185 (ISSN-L)
  • 1531-8257
DOI
10.1002/mds.28636
PMC
PMC8734457
OpenAlex
W3159341325
Cited by
42
References
42
Citations by year
2026: 4 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 8 · 2021: 1
FWCI
3.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Movement Disorders (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (IK2 BX005760)
  • National Institute on Aging (P30AG066518)
  • National Heart, Lung, and Blood Institute (R01HL155623)
  • National Institute of General Medical Sciences (TL4GM118965)
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
prodromal Parkinson's disease, onset time, gastrointestinal diseases, genitourinary diseases, skin diseases, gastroesophageal reflux, sexual dysfunction, constipation, urinary dysfunction, dermatophytosis, prostatic hyperplasia, early diagnosis, veterans
MeSH terms
Humans, Parkinson Disease, Skin, Veterans, Cohort Studies, Prodromal Symptoms

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