November 06, 2025

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Tremor, Schizophrenia, Restless Legs Syndrome Major Risk Factors For Incident Parkinson'S Disease: JAMA

Parkinson's Disease Study

Parkinson's Disease Study

A new study published in the Journal of American Medical Association Neurology suggests that the connections reported in a representative population between Parkinson's disease (PD) and specific risk factors, comorbidities, and prodromal symptoms may imply early extrastriatal and extracerebral pathology of PD.

Parkinson's disease's prodromal phase might extend for more than ten years. Recognizing the range and incidence of risk factors, comorbidities, and prodromal characteristics of Parkinson's disease can assist in expanding understanding of the illness's origins and progression, as well as identify persons at risk. As a result, Anette Schrag and colleagues undertook this study to determine the relationship between a subsequent PD diagnosis and a variety of risk factors and prodromal symptoms, such as lifestyle variables, comorbidities, and probable extracerebral manifestations of PD.

Study Design

This was a case-control study that used outpatient consultation insurance claims from patients with German statutory health insurance between January 1, 2011, and December 31, 2020. Patients with an incident diagnosis of Parkinson's disease without a prior diagnosis of parkinsonism or dementia were matched 1:1 for age, gender, area, and earliest year of outpatient visit. Previous case-control, systematic reviews, and cohort studies reporting on risk factors, comorbidities, and prodromal symptoms of Parkinson's disease were used to determine exposures. The major goal was to code previously suggested risk factors and prodromal symptoms of Parkinson's disease (PD) using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding.

Key Findings

  • There were 138,345 individuals with incident Parkinson's disease and 276,690 matched controls identified. Participants in the study were tracked for a mean (SD) of 6.0 (2.0) years.
  • Risk variables and prodromal characteristics linked with PD were traumatic brain injury, odds ratio (OR), 1.62; 95% CI, 1.36-1.92; alcohol abuse, OR, 1.32; 95% CI, 1.21-1.44; hypertension, OR, 1.29; 95% CI, 1.26-1.31; anosmia, OR, 2.16; 95% CI, 1.59-2.93; and parasomnias, OR, 1.62.
  • There were also links to restless legs syndrome, sleep apnea, migraine, epilepsy, bipolar illness, and schizophrenia.
  • Sensory abnormalities other than anosmia, such as hearing loss and alterations in skin feeling, have also been linked to Parkinson's disease.
  • Additionally, there were favorable correlations with gastrointestinal issues, skin issues, illnesses that could be inflammatory, and diabetes types 1 and 2. There were associations with tremor, restless legs syndrome, bipolar illness, and schizophrenia even five to ten years before the diagnosis.

Conclusion

In conclusion, these relationships may be caused by a genetic predisposition to PD, drug exposure, direct causation, or pathophysiologically relevant variables that contribute to the pathogenesis of PD. They may also signify potential early extrastriatal and extracerebral pathology of PD. Future investigation in prospective controlled trials is required for subtle relationships.

Reference

Schrag, A., Bohlken, J., Dammertz, L., Teipel, S., Hermann, W., Akmatov, M. K., Bätzing, J., & Holstiege, J. (2022). Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease. In JAMA Neurology. American Medical Association (AMA). https://doi.org/10.1001/jamaneurol.2022.3902

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