Cognitive Functioning in Toxic Oil Syndrome Survivors: A Case-Control Study Four Decades After the Epidemic

<b>Background:</b> Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly understood more than four decades after exposure. <b>Methods:</b> In this case-control study, 50 individuals with clinically confirmed TOS were compared to 50 healthy controls matched for age, sex, and education. All participants completed a comprehensive neuropsychological assessment, along with questionnaires evaluating fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models were adjusted for demographic and vascular risk factors, as well as for mood symptoms, fatigue, and use of central nervous system-acting medications. Structural equation modeling was used to explore the potential mediating effects of affective and fatigue symptoms on cognitive performance. <b>Results:</b> TOS survivors showed significantly poorer performance than controls in attention, executive function, processing speed, and global cognition after adjusting for demographic and vascular risk factors. However, these differences were no longer statistically significant after additional adjustment for fatigue, depression, anxiety, and central nervous system-acting medications. Structural equation modeling analyses revealed that affective symptoms-particularly fatigue-substantially mediated the relationship between TOS and cognitive performance. <b>Conclusions:</b> The cognitive profile observed mirrors that of disorders characterized by subcortical dysfunction and impaired neural connectivity, such as multiple sclerosis and vascular cognitive impairment. Although early postmortem studies in TOS did not demonstrate overt white matter lesions, our findings raise the possibility of long-lasting alterations involving both white and gray matter networks. These results emphasize the need to consider mood and fatigue symptoms when evaluating cognition in TOS survivors and point to the potential for widespread, enduring neurobiological effects stemming from the original toxic exposure.