Hippocampal Volume and Brain Tau Pathology in Opioid Use Disorder: Associations with Non-Fatal Opioid Overdose

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<0.001), but no differences between OUD individuals with a history of OD and those without (NOD) (p=0.92). We measured brain tau deposition using Positron Emission Tomography (PET) with [¹⁸F]PI-2620 in n=4 HC, n=4 OUD-NOD, and n=4 OUD-OD individuals, and found no difference in brain tau between groups. Functional MRI assessment of episodic memory showed no differences in memory performance or hippocampal activity between groups, although OUD-OD individuals had poorer performance than HC with a medium effect size (d=0.56). In summary, we confirm prior findings of smaller hippocampal volumes in participants with OUD than in HC. However, with a limited sample size, our findings do not show evidence of brain tau deposition in OUD participants with or without OD histories.