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Objective: To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches., Method: Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment., Results: Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis., Significance: We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE., (© 2020 International League Against Epilepsy.)

Objective: Subjective cognitive complaints are a frequent concern of patients with epilepsy. The Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) is a patient-reported scale validated to measure adverse cognitive effects of antiepileptic drugs (AEDs). The goals of this study were to identify predictors of patient-reported cognitive dysfunction and to assess the relationship between subjective and objective cognitive impairment., Methods: The Cleveland Clinic Knowledge Program Data Registry was used to identify adult patients seen in outpatient epilepsy clinic from January to May 2015 and who completed the following scales: ABNAS for subjective cognitive impairment, Patient Health Questionnaire (PHQ-9) for depression, Generalized Anxiety Disorder 7-item (GAD-7) scale, Quality of Life in Epilepsy (QOLIE-10), and EuroQOL five dimensions questionnaire (EQ-5D) for health-related quality of life. Topiramate (TPM) was considered a high-risk medication for cognitive impairment. Patients were categorized into groups based on total ABNAS score: subjective cognitive impairment (ABNAS>15; N=270) and no subjective cognitive impairment (ABNAS≤15; N=400). Multivariable logistic regression models were constructed to identify independent predictors of subjective cognitive impairment. In a subset of patients who had neuropsychological testing within 6months of completing the ABNAS (N=60), Pearson correlations and multivariable logistic regression models, controlling for number of AEDs, depression, and anxiety, assessed the relationship between subjective cognitive impairment and objective cognitive performance on measures of intelligence, attention/working memory, verbal fluency, naming, processing speed, manual dexterity, visuomotor processing, and verbal memory., Results: Forty percent of patients in the overall sample (N=270/670) reported cognitive impairment. The variables most strongly associated with subjective cognitive impairment were PHQ-9 score, number of AEDs, and seizure frequency. In the subset of patients with neuropsychological testing, ABNAS score was correlated with anxiety (r=0.44), depression (r=0.38), and attention/working memory (r=-0.31). After adjusting for depression and anxiety, patients who endorsed subjective cognitive impairment scored significantly lower on measures of nonverbal intelligence and attention/working memory, but not on other cognitive measures., Conclusions: Subjective cognitive impairment as reported on the ABNAS is most strongly associated with depressive symptomatology, number of AEDs, and seizure frequency, but not with most objective cognitive measures. Identifying these three predictors provides a clear framework to understand and address subjective cognitive complaints in adult patients with epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We sought to characterize cognition in individuals with germline PTEN mutations (n = 23) as well as in PTEN mutation-negative individuals with classic Cowden syndrome or Bannayan-Riley-Ruvalcaba syndrome (n = 2)., Methods: Twenty-five individuals completed a comprehensive neuropsychological evaluation. One sample t-tests and effect sizes were used to examine differences in participant test scores compared with normal controls. Composite scores were created for each patient within each of the cognitive domains assessed and classified as above average, average, or below average according to normative standards. χ(2) analyses compared these classifications to expected proportions in normal control samples., Results: The mean intelligence quotient was in the average range, and the range of intellectual functioning was very wide (from extremely low to very superior). However, in a large subset of patients, scores were lower than expected on measures of motor functioning, executive functioning, and memory recall, suggesting disruption of frontal circuits in these participants., Conclusion: This is the first study to characterize cognition in individuals with PTEN mutations and associated syndromes using a comprehensive neuropsychological battery. Contrary to previous reports suggesting an association with intellectual disability, the mean intelligence quotient was average, and there was a broad range of intellectual abilities. Specific evidence of disruption of frontal circuits may have implications for treatment compliance and cancer surveillance, and further investigation is warranted.

This study sought to determine if word-finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi-square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42-46%) as compared to patients with fewer WFDs (18-24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word-retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

When conducting neuropsychological evaluations of the elderly, it is important to compare patients' test scores to appropriate normative data to maximize diagnostic and descriptive accuracy. Many sets of normative data are now available for screening measures that assess cognitive functioning in the elderly. This article systematically reviewed available norms for 6 widely used screening measures of cognitive functioning in elderly patients. Details regarding the sample characteristics and data collection methods are provided for each set of norms, thereby providing a useful reference for clinicians.

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.

BackgroundPTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort.MethodsPatients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model.ResultsParticipants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status.LimitationsSample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments.ConclusionsSeveral canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures.Trial registrationClinicalTrials.gov Identifier NCT02461446.

Objective: Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross‐cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC‐CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background. Methods: A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation. The IC‐CoDE taxonomy was applied to derive cognitive phenotypes in the sample. Analyses of variance were conducted to examine differences in demographic and clinical characteristics across the phenotypes, and chi‐squared tests were used to determine whether the phenotype distribution differed between the Mumbai sample and published data from a multicenter US sample. Results: Using the IC‐CoDE criteria, 47% of our cohort showed an intact cognitive profile, 31% a single‐domain impairment, 16% a bidomain impairment, and 6% a generalized impairment profile. The distribution of cognitive phenotypes was similar between the Indian and US cohorts for the intact and bidomain phenotypes, but differed for the single and generalized domains. There was a larger proportion of patients with single‐domain impairment in the Indian cohort and a larger proportion with generalized impairment in the US cohort. Among patients with single‐domain impairment, a greater proportion exhibited memory impairment in the Indian cohort, whereas a greater proportion showed language impairment in the US sample, likely reflecting differences in language administration procedures and sample characteristics including a higher rate of mesial temporal sclerosis in the Indian sample. Significance: Our results demonstrate the applicability of IC‐CoDE in a group of culturally and linguistically diverse patients from India. This approach enhances our understanding of cognitive variability across cultures and enables harmonized and inclusive research into the neuropsychological aspects of epilepsy. [ABSTRACT FROM AUTHOR]

Background: Characterization of cognitive impairment (CI) in multiple sclerosis into distinct phenotypes holds promise for individualized treatments and biomarker exploration. Objective: Apply a previously validated, neuropsychologically driven diagnostic algorithm to identify a taxonomy of the type of cognitive phenotypes in multiple sclerosis. Methods: An algorithm developed and validated in other neurological diseases was applied to a cohort of 1281 people with multiple sclerosis who underwent clinical neuropsychological evaluation across three multiple sclerosis centers. A domain was marked impaired if scores on two tests within the domain fell below one of the two thresholds of interest (compared to controls; −1.0 SD and −1.5 SD below the mean). Results were then tabulated for each participant to determine the type of impairments across the sample. Results: At −1 SD threshold, 48.7% were intact, 21.6% had single-domain, 14.3% bi-domain, and 15.4% multi-domain impairment. At −1.5 SD threshold, 72.9% were intact, 14.0% had single-domain, 8.2% bi-domain, and 5.0% multi-domain impairment. Processing speed was the most frequent single-domain impairment, followed by executive function and memory. Conclusions: These findings advance the taxonomy of cognitive phenotypes in multiple sclerosis and clarify the type and distribution of possible cognitive diagnoses, pave the way for further investigation of associated biomarkers, and provide clinically meaningful information to guide individualized treatment and rehabilitation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. Method: One hundred and six patients (age 16–66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. Results: Twenty‐five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri‐Domain Phenotype (impairment in three domains), 36% met criteria for the Domain‐Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain‐specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri‐Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. Significance: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Performance validity tests (PVTs) are designed to detect nonvalid responding on neuropsychological testing, but their associations with disease-specific and other factors are not well understood in multiple sclerosis (MS). We examined PVT performance among MS patients and associations with clinical characteristics, cognition, mood, and disability status. Method: Retrospective data analysis was conducted on a sample of patients with definite MS (n = 102) who were seen for a clinical neuropsychological evaluation. Comparison samples included patients with intractable epilepsy seen for presurgical workup (n = 102) and patients with nonacute mild traumatic brain injury (mTBI; n = 50). Patients completed the Victoria Symptom Validity Test (VSVT) and validity cutoffs were defined as <16/24 and <18/24 on the hard items. Results: In this MS cohort, 14.4% of patients scored <16 on the VSVT hard items and 21.2% scored <18. VSVT hard item scores were associated with disability status and depression, but not with neuropsychological scores, T2 lesion burden, atrophy, disease duration, or MS subtype. Patients applying for disability benefits were 6.75 times more likely to score <18 relative to those who were not seeking disability. Rates of nonvalid scores were similar to the mTBI group and greater than the epilepsy group. Conclusions: This study demonstrates that nonvalid VSVT scores are relatively common among MS patients seen for clinical neuropsychological evaluation. VSVT performance in this group relates primarily to disability status and psychological symptoms and does not reflect factors specific to MS (i.e., cognitive impairment, disease severity). Recommendations for future clinical and research practices are provided. [ABSTRACT FROM AUTHOR]

With the completion of the Human Genome Project and the advent of more advanced sequencing platforms capable of high throughput genotyping at reduced cost, research on the genetics/genomics of cognition has expanded rapidly over the past several decades. This has been facilitated even further by global consortia including HapMap, 1000 Genomes Project, ENCODE, and others, which have made information regarding genetic variation and genomic functional elements readily available to all researchers. Thus, the goal of this Targeted Review is not to provide an exhaustive review of the existing literature on the role of genetic factors in cognition. Rather, we will highlight some of the most consistent findings in this field, review the research in epilepsy to date, and provide a background within which to set forth unique opportunities epilepsy may provide to further elucidate the role of genetics in cognition. [ABSTRACT FROM AUTHOR]

Loring et al. (Journal of Clinical and Experimental Neuropsychology, 2005:27;61 0-617) observed relationships between VSVT hard item performance and IQ and memory indices in epilepsy surgical candidates, with a potential confound of low FSIQ on VSVT performance. The present study replicated the Loring et al. study in a larger sample and extended their findings by examining the relationships among VSVT performance, FSIQ, and working memory. A total of 404 patients with medically intractable epilepsy completed a comprehensive neuropsychological assessment. Differences in WAIS-Ill and WMS-ffl performance were examined as a function of VSVT hard score categories as determined by Grote et al. (2000)-that is, valid, >20/24; questionable, 18-20; or invalid, <18. Quantile regression models were constructed to compare the strength of the relationship between FSIQ and VSVT at various points of the FSIQ distribution. Linear regression analyses examined working memory as a potential mediator between FSIQ and VSVT performance. The invalid group performed more poorly than the valid and questionable groups on multiple measures of intelligence and memory. The strength of the relationship between FSIQ and VSVT hard item performance decreased as FSIQ increased, and working memory mediated this relationship. Results suggest VSVT hard item scores may be impacted by working memory difficulties and/or low intellectual functioning. [ABSTRACT FROM AUTHOR]

When conducting neuropsychological evaluations of the elderly, it is important to compare patients' test scores to appropriate normative data to maximize diagnostic and descriptive accuracy. Many sets of normative data are now available for screening measures that assess cognitive functioning in the elderly. This article systematically reviewed available norms for 6 widely used screening measures of cognitive functioning in elderly patients. Details regarding the sample characteristics and data collection methods are provided for each set of norms, thereby providing a useful reference for clinicians. [ABSTRACT FROM AUTHOR]

The purpose of this study was twofold: (1) to examine the relationships among measures of cognitive symptom exaggeration (i.e., response accuracy and response latency) and (2) to examine the relationship between measures of cognitive and psychopathological symptom exaggeration. It was expected that Victoria Symptom Validity Test (VSVT) accuracy and latency measures would be significantly correlated, with invalid responders demonstrating longer response latencies. VSVT scores were also expected to correlate significantly with the Negative Impression Management (NIM) and Infrequency (INF) subscales of the Personality Assessment Inventory (PAI). VSVT and PAI data were collected from 300 patients during routine clinical neuropsychological evaluations. Results indicated that VSVT accuracy and latency measures were significantly and moderately correlated, and both types of VSVT scores were significantly, but modestly, related to NIM, but not INF. These findings suggest that VSVT response latencies may supplement accuracy scores in identifying patients who are exerting suboptimal effort on cognitive measures. These findings further suggest that measures of cognitive symptom validity only partially overlap with measures of psychopathological symptom exaggeration. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of cognitive deficits in older people with epilepsy (PWE), their ability to judge and make decisions in daily life remains unexplored. In 61 older PWE (55–90 years) from the multicenter BRain Aging and Cognition in Epilepsy (BrACE) study, we examined everyday judgment, as measured by the Test of Practical Judgment (TOP‐J: 9 questions, score range = 0–27; higher score = better judgment) and evaluated its association with clinical and demographic characteristics, global cognition, neuropsychological performance, subjective cognition, and quality of life (QOL). In our participants (mean age ± standard deviation [SD] = 66.3 ± 6.57 years; 57.4% female), >50% scored in the range observed in individuals with mild cognitive impairment (≤21) and 10% in the range similar to people with dementia (≤16). Multivariable analysis revealed that education was the only demographic factor associated with TOP‐J performance. Pearson correlation analysis revealed that lower TOP‐J scores were associated with lower global cognition, language, and abstraction/executive function. Lower TOP‐J scores were also associated with poorer QOL and self‐reported cognitive complaints. These data suggest that the TOP‐J may be a viable screening tool for early identification of reduced judgment. This could guide appropriate interventions in clinical practice, especially when older PWE present with deficits in language and executive function. [ABSTRACT FROM AUTHOR]

• Adverse social determinants of health (SDOH) factors are overrepresented in older adults with epilepsy. • Individual-level SDOH were predictors of lower cognitive performance. • Greater neighborhood deprivation was associated with worse cognitive performance. • Patients with cognitive impairment had a greater number of adverse SDOH factors. Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy. We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy. Individual-level SDOH included patient factors (quality of education, income, insurance, marital status) and early-life environmental factors (parental education and occupation, childhood employment). Neighborhood deprivation was measured with the Area Deprivation Index (ADI). Stepwise regressions were conducted to examine the independent contribution of individual-level SDOH to cognitive performance, and Spearman rho correlations were conducted to examine the relationship between ADI and cognitive performance. The SDOH profiles of patients who met the criteria for cognitive impairment were examined. After controlling for clinical variables, patient factors (public health insurance, poorer quality of education) and early-life environmental factors (lower mother's education, lower father's and mother's occupational complexity, history of childhood employment) were significant predictors of lower performance on measures of global cognition, verbal learning and memory, processing speed, and executive function. Higher ADI values (greater disadvantage) were associated with lower scores on global cognitive measures, verbal learning and memory, and executive function. Patients who met criteria for cognitive impairment had, on average, a greater number of adverse SDOH, including lower household incomes and father's education, and higher ADI values compared to those who were cognitively intact. We provide new evidence of the role of individual- and community-level SDOH on cognitive outcomes in older adults with epilepsy. This emerging literature highlights the need to examine SDOH beyond epilepsy-related clinical factors. These data could inform the development of interventions focused on increasing access to epilepsy care, education, and resources and promoting brain and cognitive health within the most at-risk communities. [ABSTRACT FROM AUTHOR]

• The Words and Faces tests are self-administered, computerized recognition memory tasks. • The Words and Faces tests show good convergent and divergent validity with gold standard neuropsychological testing in epilepsy. • The Words and Faces tests show excellent predictive accuracy in identifying patients with impairments on traditional memory measures. • Patients with epilepsy have lower scores on these automated memory measures than healthy controls. • Scores on the Words and Faces tests are associated with AED burden and seizure localization. • The Words and Faces tests are valid, computerized tools that can be used to screen for memory and other cognitive impairment in epilepsy. Cognitive impairment is prevalent in epilepsy and often presents at the time of initial diagnosis. This study sought to validate brief, self-administered, iPad-based recognition memory tasks in a sample of patients with epilepsy and to examine their screening utility in identifying patients with cognitive impairment. The Words and Faces tests were administered to 145 adult patients with epilepsy along with a neuropsychological battery. Correlation analyses examined the convergent and divergent validity of the Words and Faces tests, and a series of logistic regression analyses examined discriminative ability in identifying patients with and without cognitive impairments on neuropsychological measures. Patient performance was compared to that of a healthy control group (n = 223), and the relationship between the Words and Faces test performance and disease-related variables (i.e., antiepileptic medication burden, seizure lateralization/localization) was examined. The Words and Faces tests were positively correlated with traditional paper-and-pencil neuropsychological measures of episodic memory, with generally moderate to large effect sizes (r >.40), while correlations between the Words and Faces tests and non-memory measures were generally small in magnitude (r <.30). Patients with epilepsy had significantly lower scores on Words and Faces tests compared to healthy controls, and performance was associated with antiepileptic medication burden and seizure localization. The Words and Faces tests demonstrated good predictive accuracy in identifying any cognitive impairment (concordance (c) statistic =.77) and excellent predictive accuracy (c =.85) in identifying patients with impairments on traditional memory measures. The Words and Faces tests also demonstrated reasonable discrimination for impairments in non-memory domains including executive function, language, attention, processing speed, and visuospatial ability (c =.62 −.70). Importantly, the Words and Faces Immediate Index performed just as well as the Total Score (which included delayed memory performance), suggesting a short version of this measure is sufficient for identifying patients with cognitive impairment. The Words and Faces tests are valid, computerized tools that can be used to screen for memory and other cognitive impairment in adults with epilepsy. [ABSTRACT FROM AUTHOR]

• Little is understood about genetic factors in cognitive function and outcomes in TLE. • Results did not identify any significant relationship between PGS and cognition in TLE. • More research is needed to examine the role of genetic variation in cognition in TLE. • Future studies should seek to develop PGS specific to cognition in epilepsy. Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects. [ABSTRACT FROM AUTHOR]

• The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) produced largely stable frontal lobe epilepsy (FLE) phenotypes across centers. • Patients with FLE reported language predominant cognitive impairment. • FLE resulted in more severe cognitive impairment compared with temporal lobe epilepsy. The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23–40% cognitively intact , 24–29% single domain impairment , 13–20% bi-domain impairment , and 18–33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15–18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands. [ABSTRACT FROM AUTHOR]

• Cognitive complaints are one of the most frequent symptoms in post-COVID syndrome. • There is no consensus about the definition of cognitive impairment in this entity. • Two clusters according to the severity of cognitive dysfunction were found. • We propose a harmonization of the criteria for the definition of cognitive impairment. We aimed to develop objective criteria for cognitive dysfunction associated with the post-COVID syndrome. Four hundred and four patients with post-COVID syndrome from two centers were evaluated with comprehensive neuropsychological batteries. The International Classification for Cognitive Disorders in Epilepsy (IC-CoDE) framework was adapted and implemented. A healthy control group of 145 participants and a complementary data-driven approach based on unsupervised machine-learning clustering algorithms were also used to evaluate the optimal classification and cutoff points. According to the developed criteria, 41.2% and 17.3% of the sample were classified as having at least one cognitive domain impaired using -1 and -1.5 standard deviations as cutoff points. Attention/processing speed was the most frequently impaired domain. There were no differences in base rates of cognitive impairment between the two centers. Clustering analysis revealed two clusters, although with an important overlap (silhouette index 0.18-0.19). Cognitive impairment was associated with younger age and lower education levels, but not hospitalization. We propose a harmonization of the criteria to define and classify cognitive impairment in the post-COVID syndrome. These criteria may be extrapolated to other neuropsychological batteries and settings, contributing to the diagnosis of cognitive deficits after COVID-19 and facilitating multicenter studies to guide biomarker investigation and therapies. [ABSTRACT FROM AUTHOR]

• Patients with epilepsy often experience improved QOL, regardless of cognitive decline, as long as they have positive seizure outcomes. • Risk of worsened QOL remains for patients who experience a "double hit", particularly if they experience a decline in executive function. • Depression also plays a significant role in QOL outcomes and may be connected to changes in executive function. • Comprehensive pre-surgical neuropsychological evaluations remain important for counseling patients during the surgical process. Neurosurgery is an effective treatment option for pharmacoresistant epilepsy. Although post-surgical seizure freedom is considered the primary goal of epilepsy surgery, other factors that impact Quality of Life (QOL) are also important to consider, including post-surgical cognitive changes. This study aimed to examine the impact of post-surgical cognitive changes on QOL in the context of seizure outcomes. Participants were 196 adults with focal epilepsy who underwent either frontal (n = 27) or temporal (n = 169) lobe resection. Each participant completed pre- and post-surgical neuropsychological evaluations, and cognitive composites were constructed for the following domains: language, attention/processing speed, memory, executive function, and visuospatial skill. The Quality of Life in Epilepsy (QOLIE-10) questionnaire was used to assess QOL. Seizure outcome was determined by seizure status six months post-surgery. Eighty-one percent of patients were seizure-free post-surgery and generally reported improved QOL. While a significant portion of patient's demonstrated declines in language and verbal memory following surgery, only a decline in verbal memory was associated with worse QOL; however, this relationship was no longer significant after controlling for seizure outcome. Instead, reduced post-surgical QOL was primarily observed in those who experienced both seizure recurrence and a decline in executive function. Notably, depression was a significant covariate in all of the models. The findings from this study improve our ability to counsel patients about the trade-off between cognitive decline and seizure remittance in the greater context of overall QOL. Reassuringly, it appears that QOL is improved regardless of cognitive changes when patients have good seizure outcomes. However, for those that experience a "double hit" (i.e., cognitive decline without seizure remission), post-surgical QOL may be reduced. Changes in depression also appear to play a crucial role in QOL outcomes. [ABSTRACT FROM AUTHOR]

To characterize outcomes following pediatric epilepsy surgery across a broad range of cognitive domains using empirical methods (i.e., reliable change indices: RCIs), compare these outcomes with those based on traditional methods (i.e., standard deviation: SD), and identify factors associated with postoperative cognitive declines and/or improvements. This retrospective cohort study included 186 children who underwent surgical resection for treatment of pharmacoresistant epilepsy and who completed pre- and postoperative neuropsychological assessments. Postoperative testing occurred approximately 6.5 months after surgery and included measures of intelligence, attention/working memory, processing speed, language, executive functioning, visuospatial skills, memory, and academic achievement. Change scores for each patient were classified as decline, no change, or improvement using epilepsy-specific RCIs. Chi-square goodness of fit tests were used to compare the distribution of outcomes as classified with RCIs to those obtained using a traditional one SD cutoff. Multinomial regression analyses were conducted to identify factors associated with cognitive decline and/or improvement. While 18% of children demonstrated no postoperative declines or improvements in any cognitive domain, the majority demonstrated relatively focal changes (declines and/or improvements in 1–2 cognitive domains). Rates of postoperative decline and improvement across individual cognitive domains were variable and ranged from 4‐35% and 2–31%, respectively. Compared to RCIs, SD methodology often overestimated postoperative improvements and varied with respect to declines. Factors associated with RCI decline or improvement included preoperative performance, age at surgery, surgery site, and postoperative seizures. Results suggest substantial variability in individual cognitive outcomes approximately 6.5 months following pediatric epilepsy surgery. The differences in change distributions obtained using epilepsy-specific RCIs versus SDs highlight the need for studies using empiric methodology to study postoperative cognitive change. Variables associated with postoperative cognitive change may be used to develop multivariable prediction models in future studies to aid clinical decision-making and patient counseling. • Rates of cognitive change ~6.5 months after pediatric epilepsy surgery vary by domain. • Change defined using reliable change indices differs from standard deviations. • 18% of children showed no postoperative change in any cognitive domain. • Majority of children showed focal declines and/or improvements in 1–2 domains. • Several clinical variables were associated with postoperative cognitive change. [ABSTRACT FROM AUTHOR]

• Based on epilepsy-specific RCIs, 15% of patients showed stable cognitive performance. • Cognitive improvement occurred most frequently in visuospatial skills and processing speed. • Cognitive decline occurred most frequently in visuospatial skills and executive function. • Age and baseline cognitive performance were associated with cognitive change in many domains. To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. Forty-one pediatric patients (25 male, M age = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. Within each cognitive domain, there was a large proportion of patients (51–84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling. [ABSTRACT FROM AUTHOR]