The cognitive phenotype of juvenile absence epilepsy and its heritability: an investigation of patients and unaffected siblings

Objective: The cognitive profile of juvenile absence epilepsy (JAE) remains uncharacterized. This study aimed to: (i) elucidate the neuropsychological profile of JAE; (ii) assess cognitive trait heritability, by investigating unaffected JAE siblings; (iii) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to JME. Methods: We investigated 123 participants with a comprehensive neuropsychological test battery: 23 JAE patients, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 JME patients. We correlated clinical measures with cognitive performance data to decode effects of age of onset and duration of epilepsy. Results: JAE patients performed worse than controls on tests of verbal comprehension, working memory, verbal fluency, psychomotor speed, mental flexibility, and learning. Patients and siblings were similarly impaired on measures of verbal comprehension, phonemic and semantic fluency compared to controls. Receiver operating characteristic curves indicated successful discrimination of JAE patients and siblings from controls via linguistic measures (area under the curve [≥] .77, p [≤] .0001). Individuals with JME were more impaired on response inhibition than those with JAE. Across all patients, those with older age at onset had better performance on psychomotor speed and executive function tests. Conclusions: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including expressive language, working memory, and executive function. JAE siblings demonstrate shared impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum.