Bipolar Disorder as a Long-Term Risk Factor for Parkinson's Disease: A Nationwide Case-Control Study.

backgroundPrevious studies suggest an association between bipolar disorder (BD) and an increased risk of Parkinson's disease (PD), but the long-term temporal relationship remains unclear. Particularly, it is unclear whether the risk of PD is influenced by the duration since BD diagnosis.

objectiveThe aim was to examine the association between BD and PD across time windows extending up to 35 years before PD diagnosis.

methodsThis nationwide, register-based, nested case-control study from Finland included 22,189 incident PD patients diagnosed between 1996 and 2015 and 148,009 age-, sex-, and region-matched controls. BD diagnoses from 1972 up to the PD diagnosis date (index date) were identified from health-care registers. Conditional logistic regression was used to estimate the association between BD and PD in various exposure windows with a 0- to 35-year lag. Main analyses considered BD diagnosed at least 8 years before the index date (8-year lag).

resultsBD was diagnosed before the index date in 172 (0.87%) PD patients and 509 (0.34%) controls. Elevated PD risk was evident already with a 20-year lag between BD and PD diagnoses, with a trend toward increased risk even at 30 years. In the main analysis using the 8-year lag, BD diagnosis was associated with over a twofold higher relative risk of PD (adjusted odds ratio, 95% confidence interval: 2.32, 1.85-2.91).

conclusionsBD is associated with a significantly elevated risk of PD, observable decades before PD onset. These findings suggest that BD may reflect a long-term vulnerability to PD rather than a short-term prodromal state, emphasizing the need to explore shared pathophysiological mechanisms. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.