Development and Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Initial Results From a Multi-Center Study of Adults With Temporal Lobe Epilepsy

Objective: To describe the development and application of a consensus-based, empirically driven approach to cognitive diagnostics in epilepsy research-The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) and to assess the ability of the IC-CoDE to produce definable and stable cognitive phenotypes in a large, multi-center temporal lobe epilepsy (TLE) patient sample. Method: Neuropsychological data were available for a diverse cohort of 2,485 patients with TLE across seven epilepsy centers. Patterns of impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) using two impairment thresholds (<= 1.0 and <= 1.5 standard deviations below the normative mean). Cognitive phenotypes were derived across samples using the IC-CoDE and compared to distributions of phenotypes reported in existing studies. Results: Impairment rates were highest on tests of language, followed by memory, executive functioning, attention/processing speed, and visuospatial ability. Application of the IC-CoDE using varying operational definitions of impairment (<= 1.0 and <= 1.5 SD) produced cognitive phenotypes with the following distribution: cognitively intact (30%-50%), single-domain (26%-29%), bi-domain (14%-19%), and generalized (10%-22%) impairment. Application of the <= 1.5 cutoff produced a distribution of phenotypes that was consistent across cohorts and approximated the distribution produced using data-driven approaches in prior studies. Conclusions: The IC-CoDE is the first iteration of a classification system for harmonizing cognitive diagnostics in epilepsy research that can be applied across neuropsychological tests and TLE cohorts. This proof-of-principle study in TLE offers a promising path for enhancing research collaborations globally and accelerating scientific discoveries in epilepsy.

Automated summary

The IC-CoDE is a classification system for cognitive diagnostics in epilepsy research that produces definable and stable cognitive phenotypes. It has been applied in studies across multiple epilepsy centers and has consistently generated distributions of cognitive phenotypes.