Hippocampal and cognitive changes following non-fatal opioid overdose

Background

Despite the ongoing opioid-related public health emergency in North America, the influences of non-fatal opioid overdose on brain structure remain unclear, largely due to a paucity of pre-overdose brain images. Hippocampal atrophy, potentially with corollary cognitive deficits, associated with hypoxic insult is a possible consequence of non-fatal opioid overdose.

Research objectives

Investigate overdose-associated changes in hippocampal volume.

Methods

Linear mixed effect modelling indexed hippocampal volume changes captured in repeat brain MRI from before and after self-reported opioid overdose in 22 individuals. Data from 66 propensity-matched non-overdosing participants are the reference for unrelated changes (mean 1.7 years between scans). Participants were from a naturalistic cohort study of health of vulnerably housed people in Vancouver, Canada (N = 515, 2008–2023). Follow-up paired tests of cognitive data from assessments completed close to the time of MRIs explore possible overdose-associated changes in memory and processing speed (operationalized as composite scores respectively derived from the Hopkins Verbal Learning and Stroop tests).

Results

Participants who overdosed between MRIs had more hippocampal volume loss compared to reference participants (97 mm3 versus 25 mm3 mean loss of bilateral hippocampal volume, respectively; χ² group-time = 4.8, p = .029, B = -47.1; χ² time = 1.6, p = .211, B = -13.6). Irrespective of overdose, memory performance was unchanged around this time (overdose between assessments: V= 89.00, p = .825, rrb = -.06; reference group: V=898.50, p =.738, rrb = -.05). There was a trend towards decreasing processing speed for those who overdosed (t(18)=2.11, p =.049, Hedge’s g =0.46; means before and after overdose: 0.08 and -0.30), without changes in the reference group (t(61)=-1.10, p=.275, g =-0.14).

Conclusions

Loss of hippocampal volume and potentially processing speed may be associated with non-fatal opioid overdose.

Key messages

• In this retrospective matched cohort analysis, 22 individuals with self-reported opioid overdose between brain MRIs, matched to 66 similar participants, had greater decreases in hippocampal volume.

• Participants showed a trend towards decreased processing speed, without changes in memory, between cognitive assessments before and after self-reported opioid overdose.