Opioid use disorder and dementia risk: evidence from observational and genetic analyses in diverse ancestry cohorts

Journal article

Introduction: Opioid use disorder (OUD) may adversely affect brain health, but its role 53 in dementia risk remains poorly understood.
Methods: We investigated associations between OUD and dementia using observational data from 222,518 participants (European & African ancestry) in the Million Veteran Program, and Mendelian randomization (MR) using GWAS summary statistics from 6,066,918 individuals. Polygenic risk score (PRS) analyses were conducted in 229 opioid-naïve Lifebrain consortium participants with longitudinal MRI data.
Results: OUD was associated with increased risk of all-cause dementia (HR=1.56, 95% CI: 1.39–1.76), Alzheimer’s disease, and vascular dementia. MR supported a potential causal link between genetic liability to OUD and dementia (IVW OR=1.77, 95% CI: 1.43–2.19). Genetic variation in the μ-opioid receptor gene was also associated with dementia risk. No PRS associations were found with brain structure.
Discussion: These findings suggest a potential causal role for OUD in dementia, implicating μ-opioid receptor pathways in neurodegeneration.

Authors: Javidnia, S; Roe, JM; Karhunen, V; Gill, D; Bell, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Alzheimer's and Dementia
• Volume: 22
• Issue: 5
• Article number: e71418
• Publication date: 2026-04-24
• Acceptance date: 2026-03-24
• DOI: 10.1002/alz.71418
• EISSN: 1552-5279
• ISSN: 1552-5260
• Language: English
• Keywords: polygenic risk score; dementia; Mendelian randomization; neurodegeneration; opioid use disorder