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

Abstract

<h3>Background</h3><p>Previous 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.</p><h3>Objective</h3><p>The aim was to examine the association between BD and PD across time windows extending up to 35 years before PD diagnosis.</p><h3>Methods</h3><p>This 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).</p><h3>Results</h3><p>BD 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).</p><h3>Conclusions</h3><p>BD 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). <em>Movement Disorders</em> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>