- Bipolar disorder is associated with increased risks of all-cause dementia, Alzheimer's disease, and vascular dementia (pooled RRs 3.55, 5.08, 4.33 respectively).
- Substantial between-study heterogeneity (high I2) limits confidence in pooled estimates; the Alzheimer's disease estimate was sensitive to single-study exclusion.
- Elevated dementia risk was observed across subgroups; further high-quality longitudinal studies are required to clarify heterogeneity and subtype-specific associations.
Front Aging Neurosci. 2026 Oct 13;18:1980508. doi: 10.3389/fnagi.2026.1980508. eCollection 2026.
ABSTRACT
BACKGROUND: Bipolar disorder (BD) is associated with cognitive impairment and an increased risk of dementia; however, the magnitude of this association and subtype-specific risk patterns remain unclear. This systematic review and meta-analysis quantified the associations between BD and the risks of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD), and explored potential sources of between-study heterogeneity.
METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to September 15, 2026. Eligible cohort and case-control studies reported adjusted effect estimates for the association between BD and dementia. Hazard ratios and odds ratios were converted to risk ratios (RRs) prior to quantitative synthesis. Random- or fixed-effects models were applied according to heterogeneity. Leave-one-out sensitivity analyses, Egger’s test for publication bias, and subgroup analyses stratified by follow-up duration, sex, age at BD onset, and study design were conducted.
RESULTS: Eleven studies involving 1,536,508 participants and 90,864 all-cause dementia cases were included. BD was associated with an increased risk of all-cause dementia (RR = 3.55, 95% CI 2.48-5.07; I2 = 98.7%), AD (RR = 5.08, 95% CI 1.87-13.84; I2 = 97.2%), and VaD (RR = 4.33, 95% CI 3.06-6.13; I2 = 71.7%). Estimates for all-cause dementia and VaD were robust in sensitivity analyses, whereas the AD estimate was sensitive to the exclusion of individual studies and should therefore be interpreted cautiously. The association between BD and increased dementia risk was observed across the examined subgroups. Formal tests for subgroup differences showed no statistically significant differences according to sex or age at BD onset.
CONCLUSION: BD is associated with an increased risk of all-cause dementia, AD, and VaD. However, substantial between-study heterogeneity and the limited evidence available for specific dementia subtypes warrant cautious interpretation of the pooled estimates. Further high-quality longitudinal studies are needed to clarify the factors underlying heterogeneity and subtype-specific associations.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier [CRD420261395626].
PMID:42948010 | PMC:PMC13710222 | DOI:10.3389/fnagi.2026.1980508
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