Prospective study of bipolar disorder and neurodegenerative diseases

Abstract

Bipolar disorder (BD) is linked to an increased risk of neurodegenerative diseases such as dementia and Parkinson disease (PD), yet several uncertainties still remain and the extent to which the associations could be explained by BD-related medications (antipsychotics, lithium, and antiepileptics) was unknown. This study included 501,233 UK Biobank participants (mean [standard deviation] age, 56.5 [8.10] years; 54.4% women), free of dementia and PD at baseline. After a median 13.8 year follow-up, 9422 cases of dementia and 3457 PD cases were identified. Participants with BD had a significantly higher risk of dementia (adjusted hazard ratio [HR] 2.52, 95% CI 2.00-3.19) and PD (adjusted HR 2.88, 95% CI 2.03-4.08). Findings suggest that up to two-thirds of the association of neurodegenerative diseases with BD may be mediated by BD-related medications. Further research is needed to confirm these findings and explore the underlying mechanisms.

Fig. 1

Flowchart of study participation.

Fig. 2. Adjusted hazard ratios for neurodegenerative diseases (dementia and Parkinson disease) according to bipolar disorder in comparison with other risk factors (medications and BD-PRS).

PD Parkinson disease, BD-PRS = polygenic risk score for bipolar disorder. Risk factors associated with incident dementia (A) or Parkinson disease (B). Bipolar disorder and other risk factors were simultaneously adjusted for analyses, besides age (years), sex (women; men), ethnicity (white British; others), BMI (<25.0; 25.0–29.9; ≥30 kg/m²), smoking status (current; former; never), education level (College or University degree; A levels or equivalent; O levels or equivalent; None of the above), alcohol status (current; previous; never), regular physical activity (no; yes; others), coffee intake (<1;1–3; ≥4 cups of coffee per day), and BD-PRS (quintiles).