Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune Limbic Encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need for validated digital methods exists. We investigated whether remote digital methods could identify previously characterised cognitive impairments in ALE patients and would correlate with standard neuropsychological assessment and hippocampal volume. The cognitive performance of 21 chronic ALE patients along with 54 age-matched healthy controls was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. ALE patients performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volume of ALE patients and healthy controls correlated with online cognitive scores. Overall, these findings demonstrate that remote, online testing may facilitate the characterisation of cognitive profiles in complex neurological diseases.