Abstracts

Rationale: Cognitive impairment is common amongst people with chronic epilepsy; in particular, high rates of autobiographical memory deficits are seen across focal epilepsy syndromes. Potential causal factors, however, are typically gleaned from fairly heterogeneous populations of patients (e.g., "focal epilepsy", "temporal lobe epilepsy") rather than searching for more individualized factors that might provide focused targets for treatment development. This study investigates the antecedents of autobiographic memory impairments in epilepsy patients with early (childhood/adolescence) versus late (adulthood) disease onset, with the aim of uncovering distinct predictors of memory decrement. It is hypothesized that memory impairments in people with seizure onset during the critical neurodevelopmental period of childhood/adolescence will be linked to epilepsy-related factors. In contrast, impairments in those with adult onset will be more strongly related to non-epilepsy factors known to impact on recall, such as depressive symptoms. Methods: In total, 166 adults participated in this study between 2010-2015: 92 patients with focal epilepsy recruited from the Comprehensive Epilepsy Programme at Austin Health (59% female; aged 20?"69 years), whose performances on cognitive and psychiatric measures were compared to that of 74 sociodemographically-matched healthy controls (62% female; 21?"69 years). Predictors of autobiographic memory impairment were contrasted between patients with early onset (n=47) versus late onset (n=45) using multiple regression analyses. Results: Overall, people with epilepsy performed significantly worse on measures of both semantic and episodic autobiographic memory and showed markedly high rates of depressive symptoms and disorder (P < .001; medium-very large effect sizes). Reduced autobiographic memory in early onset patients was associated with young age at onset, more frequent seizures, and reduced working memory. In contrast, the difficulty that late onset patients' had in recalling autobiographical information was linked to depression and the presence of a MRI-identified lesion. Conclusions: This study reveals that memory deficits in people with focal epilepsy have differing antecedents depending on the timing of the disease onset. While neurobiological factors strongly underpin reduced autobiographical function in early onset patients, psychological maladjustment plays a major role in the impairments of later onset patients. More broadly, these findings support the practice of subtyping patients according to distinct clinical characteristics to find individualized predictors of cognitive dysfunction. Funding: The work of Professor Jackson is supported by an NHMRC Program Grant (#400121), an NHMRC Practitioner Fellowship (#527800), and by the Victorian Government Operational Infrastructure Support Grant Scheme.