Anxiety and depression as prodromes of Parkinson's disease: prospective findings from the Moli-sani study.
Level 3 - non-randomized controlled study
Prospective cohort study with propensity score-weighted Cox proportional hazards analysis.
PubMed 41772237 · doi:10.1007/s00415-026-13710-7
What was done
Researchers evaluated 23,395 participants (52% women, mean age 55 ± 12 years) free of Parkinson's disease (PD) at baseline from the Italian Moli-sani prospective cohort study over a median 15-year follow-up (337,372 person-years). Exposure was categorized into non-exposed (n = 20,033), individuals with anxiety or depression confirmed by both self-report and documented medication use (n = 1,760), and those meeting only one criterion (n = 1,602). Incident PD cases were identified via regional health records and neurologist validation. Hazard ratios were estimated using propensity score-based inverse probability-weighted Cox models.
What was found
A total of 306 incident PD cases occurred. Participants with both self-reported and medically treated anxiety or depression had double the hazard of developing PD compared to non-exposed individuals (HR = 2.02, 95% CI: 1.45–2.80), which remained consistent when restricted to neurologist-validated PD cases (144 cases; HR = 1.96, 95% CI: 1.21–3.17). Risk was highest among individuals treated for both anxiety and depression (n = 395; HR = 3.18, 95% CI: 1.90–5.31). Meeting only one criterion showed no significant association. The association progressively attenuated and nearly disappeared when the interval between psychiatric exposure and study exit exceeded 10 years.
Why it matters
This study defines a distinct 10-year prodromal time window during which pharmacologically treated affective disorders are tied to impending Parkinson's motor onset, helping refine early screening and neuroprotective trial windows.
Limits
Psychiatric exposure classification relied partly on baseline self-reports and prescribed medications, leaving unmedicated or intermittent psychiatric episodes potentially misclassified. Causality cannot be definitively established due to the observational design, and unmeasured lifestyle or biological confounders may remain despite propensity-score weighting.
Cited by
- supports Anxiety and depression can precede the onset of motor symptoms in Parkinson's disease by up to two years.