Cognitive reserve depends on cortical neurochemistry to predict memory after partner-inflicted brain injury

Memory problems are commonplace following brain injury (BI). However, it remains unclear why some report memory problems while others do not, especially following repeated neurotrauma. Cognitive reserve has been widely hypothesized to account for this variation, but testing this account has yielded inconsistent results and proven difficult, likely as it requires a sample spanning a wide range of BI burden with concurrent neuroimaging and cognitive measurement. Here, we combined a wide range of cognitive assessments with measures of neuronal health using magnetic resonance spectroscopy across three brain regions in 62 women who had experienced physical intimate partner violence. Partner-inflicted BI counts ranged from 0 to 420, yet we found that the number of BIs alone did not explain the variance in memory outcomes. Among a small subset with high BI exposure ([≥]10 BIs; n = 11), BI count explained 5% of the variance in delayed recall, the primary memory outcome, whereas cognitive reserve, inferred from a measure of premorbid functioning, explained almost half (unadjusted in-sample associations). In the full cohort, cognitive reserve predicted memory only among the most heavily injured participants. In a separate model, cognitive reserve predicted memory only when creatine-referenced total N-acetylaspartate, a marker of neuronal health, was lower in the posterior cingulate gyrus and dorsolateral prefrontal cortex. Ultimately, our findings provide behavioral and neurochemical evidence consistent with the cognitive reserve hypothesis and shed new light on why, despite a high burden of neurotrauma, memory may remain resilient.