Risk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses

Acta Psychiatr Scand. 2020 Jun;141(6):510-521. doi: 10.1111/acps.13153. Epub 2020 Feb 11.


Objectives: To assess whether bipolar disorder (BD) increases the rate of dementia and whether lithium is related to a lower risk of dementia in BD.

Methods: A total of 10 studies (6859 BD; 487 966 controls) were included in the meta-analysis to test whether BD is a risk factor for dementia. In addition, five studies (6483 lithium; 43 496 non-lithium) were included in the meta-analysis about the potential protective effect of lithium in BD.

Results: BD increases the risk of dementia (odds ratio (OR): 2.96 [95% CI: 2.09-4.18], P < 0.001), and treatment with lithium decreases the risk of dementia in BD (OR: 0.51 [95% CI: 0.36-0.72], P < 0.0001). In addition, secondary findings from our systematic review showed that the risk of progression to dementia is higher in BD than in major depressive disorder (MDD). Moreover, the number of mood episodes predicted the development of dementia in BD.

Conclusion: Individuals with BD are at higher risk of dementia than both the general population or those with MDD. Lithium appears to reduce the risk of developing dementia in BD.

Keywords: Alzheimer’s; aging; bipolar disorder; dementia; depression; lithium; mania; neuroprogression; prevention; treatment.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Affect
  • Bipolar Disorder / complications*
  • Bipolar Disorder / drug therapy*
  • Dementia / etiology*
  • Dementia / prevention & control*
  • Depressive Disorder, Major / complications
  • Humans
  • Lithium Compounds / pharmacology*
  • Lithium Compounds / therapeutic use*
  • Risk Factors


  • Lithium Compounds