Cognitive phenotypes in late-onset epilepsy: results from the atherosclerosis risk in communities study

Abstract

IntroductionCognitive phenotyping is a widely used approach to characterize the heterogeneity of deficits in patients with a range of neurological disorders but has only recently been applied to patients with epilepsy. In this study, we identify cognitive phenotypes in older adults with late-onset epilepsy (LOE) and examine their demographic, clinical, and vascular profiles. Further, we examine whether specific phenotypes pose an increased risk for progressive cognitive decline.MethodsParticipants were part of the Atherosclerosis Risk in Communities Study (ARIC), a prospective longitudinal community-based cohort study of 15,792 individuals initially enrolled in 1987–1989. LOE was identified from linked Centers for Medicare and Medicaid Services claims data. Ninety-one participants with LOE completed comprehensive testing either prior to or after seizure onset as part of a larger cohort in the ARIC Neurocognitive Study in either 2011–2013 or 2016–2017 (follow-up mean = 4.9 years). Cognitive phenotypes in individuals with LOE were derived by calculating test-level impairments for each participant (i.e., ≤1 SD below cognitively normal participants on measures of language, memory, and executive function/processing speed); and then assigning participants to phenotypes if they were impaired on at least two tests within a domain. The total number of impaired domains was used to determine the cognitive phenotypes (i.e., Minimal/No Impairment, Single Domain, or Multidomain).ResultsAt our baseline (Visit 5), 36.3% met criteria for Minimal/No Impairment, 35% for Single Domain Impairment (with executive functioning/ processing speed impaired in 53.6%), and 28.7% for Multidomain Impairment. The Minimal/No Impairment group had higher education and occupational complexity. There were no differences in clinical or vascular risk factors across phenotypes. Of those participants with longitudinal data (Visit 6; n = 24), 62.5% declined (i.e., progressed to a more impaired phenotype) and 37.5% remained stable. Those who remained stable were more highly educated compared to those that declined.DiscussionOur results demonstrate the presence of identifiable cognitive phenotypes in older adults with LOE. These results also highlight the high prevalence of cognitive impairments across domains, with deficits in executive function/processing speed the most common isolated impairment. We also demonstrate that higher education was associated with a Minimal/No Impairment phenotype and lower risk for cognitive decline over time.

Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research?

“…Approximately one‐third of our cohort was classified as impaired based on the IC‐CoDE taxonomy, a similar rate to previous studies in older adults with epilepsy, 19 compared to 54% classified as abnormal based on the MoCA (cutoff of <26). The recommended cutoff of <26 had an overall 72% accuracy, correctly classifying approximately 88% of the patients who were impaired based on the IC‐CoDE taxonomy.…”

“…The IC‐CoDE phenotype classification is based on the number of impaired domains (at least two impaired tests), with single‐domain defined as impairment in one cognitive domain, bi‐domain defined as impairment in two domains, generalized defined as impairment in three or more domains, and intact defined as no impairment in any cognitive domain. We used <1 standard deviation below the normative mean as the impairment cutoff given that it has been shown to balance sensitivity and stability of impairment when examining profiles of scores 17 and has been previously used in studies with older adults with epilepsy 18,19 . Given that the purpose of this study was to examine the MoCA's ability to detect cognitive impairment based on the IC‐CoDE classification (impaired vs. intact), patients with either single, bi‐domain, or generalized impairments were combined into one group (i.e., IC‐CoDE Impaired), whereas as those with no impaired domains were classified as IC‐CoDE Intact.…”

“…We used <1 standard deviation below the normative mean as the impairment cutoff given that it has been shown to balance sensitivity and stability of impairment when examining profiles of scores 17 and has been previously used in studies with older adults with epilepsy. 18 , 19 Given that the purpose of this study was to examine the MoCA's ability to detect cognitive impairment based on the IC‐CoDE classification (impaired vs. intact), patients with either single, bi‐domain, or generalized impairments were combined into one group (i.e., IC‐CoDE Impaired), whereas as those with no impaired domains were classified as IC‐CoDE Intact.…”