Incidence of Parkinson's disease, dementia, cerebrovascular disease and stroke in bipolar disorder compared to other psychiatric disorders: An electronic health records network study of 66 million people.

Objectives: Bipolar disorder has been associated with an increased risk for neurodegenerative diseases, but uncertainties remain. The risk relative to other psychiatric disorders is not established.

Methods: We used a federated electronic health records network of 66 million people including over 700,000 with bipolar disorder. We assessed incidence of a first diagnosis of Parkinson's disease, dementia, cerebrovascular disease and stroke, in patients at least 1 year after diagnosis of bipolar disorder. Rates were compared to propensity score matched cohorts of subjects with mixed disorders, recurrent major depressive disorder (MDD) or schizophrenia.

Results: Parkinson's disease was commoner in bipolar disorder compared to all three cohorts (odds ratios [OR] ranging from 1.26 to 2.65). Dementia incidence was greater in bipolar disorder than in mixed disorders (OR = 1.61) or MDD (OR = 1.40), but not different from schizophrenia (OR = 0.96). Cerebrovascular disease and stroke were commoner in bipolar disorder than in schizophrenia (OR = 1.35) or mixed disorders (OR = 1.20) and equivocally raised compared to MDD. Results were robust to a wide range of confounding demographic, diagnostic and medication risk factors for neurodegenerative disorders.

Conclusions: Bipolar disorder confers an elevated risk for developing neurodegenerative disorders and cerebrovascular disease compared to other major adult psychiatric disorders. The results cannot be attributed to recognised confounders. The results are consistent with neuroprogressive views of bipolar disorder. The underlying mechanisms remain to be discovered.