Schedule of Events | Symposia

Opioid use disorder and brain health: observational and genetic associations

Poster Session E - Monday, March 31, 2025, 2:30 – 4:30 pm EDT, Back Bay Ballroom/Republic Ballroom

Sara Javidnia¹ (sara.javidnia@psych.ox.ac.uk); ¹Oxford University

Background: The long-term impact of opioid use disorder (OUD) on brain health has been little explored although of potentially high public health importance. Objectives: To investigate the potential causal impact of OUD on later life brain health outcomes, including dementia, stroke and brain structure. Methods: Observational and Mendelian randomization (MR) analyses were conducted. Participants in observational analyses were from the US Million Veteran Program (MVP). Cox proportional hazards examined the association between electronic health record (EHR)-derived OUD diagnoses and incident dementia in European and African ancestry populations. Two-sample MR explored associations between genetic predisposition to OUD and dementia, as well as brain structure. Analyses included cis-MR for genetically-proxied opioid receptor perturbation, Bayesian colocalization, and polygenic risk score analyses of longitudinal brain changes in non-opioid users from the Lifebrain project (n=229). Results: Amongst 222,518 MVP participants, 8397 developed dementia. Participants with OUD (n=9,399) were younger and more likely to be male. OUD was associated with a higher risk of all-cause (HR=1.56[1.39,1.76];p=2.23×10⁻¹³), Alzheimer’s (HR=1.40[1.04,1.87];p=0.02), and vascular dementia (HR=1.49[1.19,1.86];p=0.0004). Genetically-proxied OUD also increased dementia risk, with a doubling in OUD prevalence associated with 77% higher odds (IVW OR=1.77[1.43,2.19];p=1.69×10⁻⁷). Perturbations in mu-opioid receptor genes were associated with dementia risk. No significant associations with brain structure were found in non-opioid users or non-European ancestry groups. Conclusions: These findings suggest a potential causal impact of opioid use disorder on dementia. Genetic analyses supported an aetiological role of mu-opioid receptor pathways. Further pharmacovigilance and investigation into opioids' long-term effects on brain health are warranted.

Topic Area: LONG-TERM MEMORY: Other