Cognitive phenotypes in frontal lobe epilepsy

Arrotta, Kayela; Reyes, Anny; Kaestner, Erik; McDonald, Carrie R.; Hermann, Bruce P.; Barr, William; Sarmey, Nehaw; Sundar, Swetha J.; Kondylis, Efstathios; Najm, Imad; Bingaman, William; Busch, Robyn M.

doi:10.1111/epi.17260

Cited by 16 publications

(17 citation statements)

References 52 publications

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“…Furthermore, the visuospatial domain was the least impaired across a sample of 2485 patients with drug-resistant TLE and only 1–2% of the single-domain phenotype had an isolated visuospatial impairment. Regarding visual memory, studies that have included visual memory tests 10 , 18 , 37 , 60 have combined verbal and visual memory tests into one domain and it remains to be determined if an isolated visual memory phenotype exists. A recent meta-analysis explored the lateralizing capabilities of non-verbal memory tests in patients with unilateral TLE and noted that the stimulus type (e.g.…”

Section: Discussionmentioning

confidence: 99%

Moving towards a taxonomy of cognitive impairments in epilepsy: application of latent profile analysis to 1178 patients with temporal lobe epilepsy

Reyes

Hermann

Busch

et al. 2022

Brain Communications

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In efforts to understand the cognitive heterogeneity within and across epilepsy syndromes, cognitive phenotyping has been proposed as a new taxonomy aimed at developing a harmonized approach to cognitive classification in epilepsy. Data- and clinically-driven approaches have been previously used with variability in the phenotypes derived across studies. In our study, we utilize latent profile analysis to test several models of phenotypes in a large multicenter sample of patients with temporal lobe epilepsy and evaluate their demographic and clinical profiles. For the first time, we examine the added value of replacing missing data and examine factors that may be contributing to missingness. A sample of 1,178 participants met inclusion criteria for the study, which included a diagnosis of temporal lobe epilepsy and availability of comprehensive neuropsychological data. Models with 2-5 classes were examined using latent profile analysis and the optimal model was selected based on fit indices, posterior probabilities, and proportion of sample sizes. The models were also examined with imputed data to investigate the impact of missing data on model selection. Based on the fit indices, posterior probability, and distinctiveness of the latent classes, a 3-class solution was the optimal solution. This 3-class solution was comprised of a group of patients with multidomain impairments, a group with impairments predominantly in language, and a group with no impairments. Overall, the Multidomain group demonstrated a worse clinical profile and was comprised of a greater proportion of patients with mesial temporal sclerosis, longer disease duration, and higher number of antiseizure medications. The 4-Class and 5-Class solutions demonstrated the lowest probabilities of group membership. Analyses with imputed data demonstrated that the 4-Class solution was the optimal solution; however, there was weak agreement between the missing and imputed datasets for the 4-Class solutions (κ = .288, p < .001). This study represents the first to use latent profile analysis to test and compare multiple models of cognitive phenotypes in temporal lobe epilepsy, and to determine the impact of missing data on model fit. We found that the three-phenotype model was the most meaningful based on several fit indices and produced phenotypes with unique demographic and clinical profiles. Our findings demonstrate that latent profile analysis is a rigorous method to identify phenotypes in large, heterogeneous epilepsy samples. Furthermore, this study highlights the importance of examining the impact of missing data in phenotyping methods. Our latent profile analysis-derived phenotypes can inform future studies aimed at identifying cognitive phenotypes in other neurological disorders.

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Section: Discussionmentioning

confidence: 99%

Moving towards a taxonomy of cognitive impairments in epilepsy: application of latent profile analysis to 1178 patients with temporal lobe epilepsy

Reyes

Hermann

Busch

et al. 2022

Brain Communications

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“…32 Across all our participants, however, both letter fluency and similarities had higher correlations with language than with executive function measures (Supplementary Methods), and were thus considered as language measures. 33…”

Section: Methodsmentioning

confidence: 99%

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

Caciagli

Ratcliffe

Xiao

et al. 2022

Preprint

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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.

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“…In efforts to better understand this heterogeneity, investigations have focused on identifying patterns of cognitive deficits or cognitive phenotypes 9 . Across studies in focal epilepsy, three to four phenotypes have been identified with stable and reproducible cognitive patterns, including a group with generalized impairment, a group with focal deficits, and a third group with intact profiles 9–18 . This phenotype approach has proven useful for establishing links between distinct neural abnormalities and patterns of cognitive impairment 11,12,14,16 and predicting cognitive progression 10 and postoperative outcomes 18 .…”

Section: Introductionmentioning

confidence: 99%

“…9 Across studies in focal epilepsy, three to four phenotypes have been identified with stable and reproducible cognitive patterns, including a group with generalized impairment, a group with focal deficits, and a third group with intact profiles. [9][10][11][12][13][14][15][16][17][18] This phenotype approach has proven useful for establishing links between distinct neural abnormalities and patterns of cognitive impairment 11,12,14,16 and predicting cognitive progression 10 and postoperative outcomes. 18 Despite an extensive literature focused on the neuropsychological syndromes of the epilepsies and the recent advances in cognitive phenotyping, there are no evidence-based criteria for guiding cognitive diagnostics in epilepsy research.…”

Section: Introductionmentioning

confidence: 99%

Establishing the cross‐cultural applicability of a harmonized approach to cognitive diagnostics in epilepsy: Initial results of the International Classification of Cognitive Disorders in Epilepsy in a Spanish‐speaking sample

et al. 2023

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Objective This study was undertaken to evaluate the cross‐cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC‐CoDE) to a cohort of Spanish‐speaking patients with temporal lobe epilepsy (TLE) living in the United States. Methods Eighty‐four Spanish‐speaking patients with TLE completed neuropsychological measures of memory, language, executive function, visuospatial functioning, and attention/processing speed as part of the Neuropsychological Screening Battery for Hispanics. The contribution of demographic and clinical variables to cognitive performance was evaluated. A sensitivity analysis was conducted by examining the base rates of impairment across several impairment thresholds. The IC‐CoDE taxonomy was then applied, and the base rate of cognitive phenotypes for each cutoff was calculated. The distribution of phenotypes was compared to the published IC‐CoDE taxonomy data, which utilized a large, multicenter cohort of English‐speaking patients with TLE. Results Across the different impairment cutoffs, memory was the most impaired cognitive domain, with impairments in list learning ranging from 50% to 78%. Application of the IC‐CoDE taxonomy utilizing a −1.5‐SD cutoff revealed an intact cognitive profile in 47.6% of patients, single‐domain impairment in 23.8% of patients, bidomain impairment in 14.3% of patients, and generalized impairment in 14.3% of the sample. This distribution was comparable to the phenotype distribution observed in the IC‐CoDE validation sample. Significance We demonstrate a similar pattern and distribution of cognitive phenotypes in a Spanish‐speaking epilepsy cohort compared to an English‐speaking sample. This suggests stability in the underlying phenotypes associated with TLE and applicability of the IC‐CoDE for guiding cognitive diagnostics in epilepsy research that can be applied to culturally and linguistically diverse samples.

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Cognitive phenotypes in frontal lobe epilepsy

Cited by 16 publications

References 52 publications

Moving towards a taxonomy of cognitive impairments in epilepsy: application of latent profile analysis to 1178 patients with temporal lobe epilepsy

Moving towards a taxonomy of cognitive impairments in epilepsy: application of latent profile analysis to 1178 patients with temporal lobe epilepsy

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

Establishing the cross‐cultural applicability of a harmonized approach to cognitive diagnostics in epilepsy: Initial results of the International Classification of Cognitive Disorders in Epilepsy in a Spanish‐speaking sample

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