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Public Health.

Jenna Najar1,2,3, Robert Sigström2, Lina Jonsson2

  • 1Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Netherlands.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary

Genetic risk for Alzheimer's disease (AD) increases dementia risk in individuals with bipolar disorder (BD). This finding clarifies the link between BD and dementia, aiding in risk assessment and prevention strategies.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Individuals with bipolar disorder (BD) exhibit a higher risk of dementia.
  • The specific genetic factors contributing to this increased risk remain largely unknown.
  • Understanding the genetic overlap between BD and dementia is crucial for developing effective interventions.

Purpose of the Study:

  • To investigate the association between genetic risk factors for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) and the risk of dementia in individuals with bipolar disorder (BD).
  • To explore the role of APOE ε4 carriership and polygenic risk scores (PGS) for AD and DLB in dementia development among BD patients.

Main Methods:

  • Utilized data from 2,238 genotyped individuals with BD from the Swedish Bipolar Collection (SWEBIC).
  • Identified dementia diagnoses using national patient register codes.
  • Calculated non-APOE polygenic scores (PGS) for AD and DLB and assessed APOE ε4 carriership.
  • Employed Cox regression analyses to examine the relationship between genetic factors and dementia risk, adjusting for covariates.

Main Results:

  • APOE ε4 carriership was significantly associated with an increased risk of dementia in individuals with BD (HR: 1.88, p=0.007).
  • A higher polygenic risk score for Alzheimer's disease (AD-PGS) was also linked to increased dementia risk (HR: 1.34, p=0.01).
  • No significant association was found between the polygenic risk score for dementia with Lewy bodies (DLB-PGS) and dementia risk in this cohort.

Conclusions:

  • Genetic predisposition to Alzheimer's disease contributes to the development of dementia in individuals with bipolar disorder.
  • These findings illuminate the shared genetic underpinnings between AD and BD, offering insights into dementia etiology in BD patients.
  • The results support the potential for genetic risk stratification and targeted preventive strategies for dementia in the BD population.