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Updated: May 23, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Opioid use disorder and dementia risk: evidence from observational and genetic analyses in diverse ancestry cohorts
Sara Javidnia1, James M Roe2,3, Ville Karhunen4
1Department of Psychiatry and Centre for Integrative Neuroimaging, University of Oxford, London, UK.
Introduction:
Opioid use disorder (OUD) may adversely affect brain health, but its role in dementia risk remains poorly understood.
Methods:
We investigated associations between OUD and dementia using observational data from 222,518 participants (European and African ancestry) in the Million Veteran Program and Mendelian randomization (MR) using genome-wide association study summary statistics from 6,066,918 individuals. Polygenic risk score (PRS) analyses were conducted in 229 opioid-naïve Lifebrain consortium participants with longitudinal magnetic resonance imaging data.
Results:
OUD was associated with increased risk of all-cause dementia (hazard ratio = 1.56, 95% confidence interval [CI]: 1.39 to 1.76), Alzheimer's disease, and vascular dementia. MR supported a potential causal link between genetic liability to OUD and dementia (inverse variance weighted odds ratio = 1.77, 95% CI: 1.43 to 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.
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