Hippocampal volume and brain tau pathology in opioid use disorder: Associations with non-fatal opioid overdose

• Individuals with OUD had lower hippocampal volume but no evidence of brain tau deposition, compared to healthy controls. • History of opioid OD did not affect hippocampal volume or brain tau deposition. • Individuals with a history of opioid OD had poorer memory performance than healthy controls. Opioid use disorder (OUD) is associated with high rates of overdose (OD)-related morbidity and mortality. OD can cause hypoxic-ischemic injury to oxygen-sensitive brain regions such as the hippocampus. Post-mortem studies show Alzheimer’s disease-like hyperphosphorylated tau pathology in the brains of individuals with OUD. Neurocognitive impairments in individuals with OUD may reflect incipient dementia and contribute to poor clinical outcomes. Alternatively, OUD and OD could be independent risk factors for Alzheimer’s disease. To date, no study has evaluated the effects of non-fatal ODs or chronic OUD on hippocampal volume and tau deposition in the human brain in vivo . To fill this gap, we examined hippocampal volumes in OUD individuals (n=60) and healthy controls (HC, n=30) using T1-weighted magnetic resonance imaging (MRI). We found lower bilateral hippocampal volumes in OUD patients than HCs (p