Do prescription stimulants increase risk of Parkinson's disease among adults with attention-deficit hyperactivity disorder? A retrospective cohort study.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder in older adults that is associated with neuroinflammation, oxidative stress, and characterized by loss of dopaminergic cells. Illicit stimulants increase oxidative stress and are associated with increased risk of PD. Prescription stimulants are similar in mechanism to illicit stimulants, yet their influence on PD is not well described. This study aims to determine if prescription stimulants influence risk of PD among older adults with attention-deficit and hyperactivity disorder (ADHD).

Methods: We implemented a retrospective observational cohort design utilizing the TriNetX database which sources from the electronic health records of 57 healthcare organizations. Inclusion criteria were ADHD diagnosis and age ≥50. Those exposed to stimulants and the unexposed controls were matched based on demographics and known risk factors for PD. The outcome of interest was the incidence of PD over a 30-year follow-up period. We utilized TriNetX software for hazard ratio (HR) analysis.

Results: Among the 59,471 individuals treated with prescription stimulants 131 of them developed PD, and there were 272 individuals who developed PD that were not prescribed stimulants. This analysis yielded a HR of 0.419 (HR = 0.419 [95% CI 0.34, 0.516], P = 0.0013).

Conclusion: Illicit stimulants are associated with increased risk of PD, but this study suggests prescribed stimulants may not impart that same risk. The reduced risk in this cohort may be due to protection from illicit substance use and oxidative stress, however additional study exploring the relationship between prescription stimulants and PD is warranted.