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 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.
We previously identified 4 empirically derived mild cognitive impairment (MCI) subtypes via cluster analysis within the Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrated high ...correspondence between patterns of cortical thinning at baseline and each cognitive subtype. We aimed to determine whether our MCI subtypes demonstrate unique longitudinal atrophy patterns.
ADNI participants (295 with MCI and 134 cognitively normal CN) underwent annual structural MRI and neuropsychological assessments. General linear modeling compared vertex-wise differences in cortical atrophy rates between each MCI subtype and the CN group. Linear mixed models examined trajectories of cortical atrophy over 3 years within lobar regions of interest.
Compared to the CN group, those with amnestic MCI (memory deficit) initially demonstrated greater atrophy rates within medial temporal lobe regions that became more widespread over time. Those with dysnomic/amnestic MCI (naming/memory deficits) showed greater atrophy rates largely localized to temporal lobe regions. The mixed MCI (impairment in all cognitive domains) group showed greater atrophy rates in widespread regions at all time points. The cluster-derived normal group, who had intact neuropsychological performance and normal cortical thickness at baseline despite their MCI diagnosis via conventional diagnostic criteria, continued to show normal cognition and minimal cortical atrophy over 3 years.
ADNI's purported amnestic MCI sample produced more refined cognitive subtypes with unique longitudinal cortical atrophy rates. These novel MCI subtypes reliably reflect underlying atrophy, reduce false-positive diagnostic errors, and improve prediction of clinical course. Such improvements have implications for the selection of participants for clinical trials and for providing more precise risk assessment for individuals diagnosed with MCI.
Cognitive phenotypes in frontal lobe epilepsy Arrotta, Kayela; Reyes, Anny; Kaestner, Erik ...
Epilepsia (Copenhagen),
July 2022, 2022-07-00, 20220701, Letnik:
63, Številka:
7
Journal Article
Recenzirano
Odprti dostop
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.
There is growing evidence that bilingualism can induce neuroplasticity and modulate neural efficiency, resulting in greater resistance to neurologic disease. However, whether bilingualism is ...beneficial to neural health in the presence of epilepsy is unknown. We tested whether bilingual individuals with temporal lobe epilepsy (TLE) have improved whole-brain structural white matter network organization.
Healthy controls and individuals with TLE recruited from 2 specialized epilepsy centers completed diffusion-weighted MRI and neuropsychological testing as part of an observational cohort study. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory. Global analyses compared network integration (path length) and specialization (transitivity) in TLE vs controls and in a 2 (left vs right TLE) × 2 (bilingual vs monolingual) model. Local analyses compared mean local efficiency of predefined frontal-executive and language (i.e., perisylvian) subnetworks. Exploratory correlations examined associations between network organization and neuropsychological performance.
A total of 29 bilingual and 88 monolingual individuals with TLE matched on several demographic and clinical variables and 81 age-matched healthy controls were included. Globally, a significant interaction between language status and side of seizure onset revealed higher network organization in bilinguals compared with monolinguals but only in left TLE (LTLE). Locally, bilinguals with LTLE showed higher efficiency in frontal-executive but not in perisylvian networks compared with LTLE monolinguals. Improved whole-brain network organization was associated with better executive function performance in bilingual but not monolingual LTLE.
Higher white matter network organization in bilingual individuals with LTLE suggests a neuromodulatory effect of bilingualism on whole-brain connectivity in epilepsy, providing evidence for neural reserve. This may reflect attenuation of or compensation for epilepsy-related dysfunction of the left hemisphere, potentially driven by increased efficiency of frontal-executive networks that mediate dual-language control. This highlights a potential role of bilingualism as a protective factor in epilepsy, motivating further research across neurologic disorders to define mechanisms and develop interventions.
Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical ...atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer's disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer's disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.
Individuals with left temporal lobe epilepsy (TLE) have a higher rate of atypical (i.e., bilateral or right hemisphere) language lateralization compared to healthy controls. In addition, bilinguals ...have been observed to have a less left-lateralized pattern of language representation. We examined the combined influence of bilingual language experience and side of seizure focus on language lateralization profiles in TLE to determine whether bilingualism promotes re-organization of language networks. Seventy-two monolingual speakers of English (21 left TLE; LTLE, 22 right TLE; RTLE, 29 age-matched healthy controls; HC) and 24 English-dominant bilinguals (6 LTLE, 7 RTLE, 11 HC) completed a lexical-semantic functional MRI task and standardized measures of language in English. Language lateralization was determined using laterality indices based on activations in left vs right homologous perisylvian regions-of-interest (ROIs). In a fronto-temporal ROI, LTLE showed the expected pattern of weaker left language lateralization relative to HC, and monolinguals showed a trend of weaker left language lateralization relative to bilinguals. Importantly, these effects were qualified by a significant group by language status interaction, revealing that bilinguals with LTLE had greater rightward language lateralization relative to monolingual LTLE, with a large effect size particularly in the lateral temporal region. Rightward language lateralization was associated with better language scores in bilingual LTLE. These preliminary findings suggest a combined effect of bilingual language experience and a left hemisphere neurologic insult, which may together increase the likelihood of language re-organization to the right hemisphere. Our data underscore the need to consider bilingualism as an important factor contributing to language laterality in patients with TLE. Bilingualism may be neuroprotective pre-surgically and may mitigate post-surgical language decline following left anterior temporal lobectomy, which will be important to test in larger samples.
•Bilingualism and a left seizure focus jointly influence language lateralization on fMRI.•Most bilinguals with left-sided epilepsy showed atypical language lateralization.•Atypical language was associated with better language function in bilinguals.
Objective
To identify neuroimaging and clinical biomarkers associated with a language‐impaired phenotype in refractory temporal lobe epilepsy (TLE).
Methods
Eighty‐five patients with TLE were ...characterized as language‐impaired (TLE‐LI) or non–language‐impaired (TLE‐NLI) based on comprehensive neuropsychological testing. Structural magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) were obtained in patients and 47 healthy controls (HC). fMRI activations and cortical thickness were calculated within language regions of interest, and fractional anisotropy (FA) was calculated within deep white matter tracts associated with language. Analyses of variance were performed to test for differences among the groups in imaging measures. Receiver operator characteristic curves were used to determine how well different clinical versus imaging measures discriminated TLE‐LI from TLE‐NLI.
Results
TLE‐LI patients showed significantly less activation within left superior temporal cortex compared to HC and TLE‐NLI, regardless of side of seizure onset. TLE‐LI also showed decreased FA in the inferior longitudinal fasciculus and arcuate fasciculus compared to HC. Cortical thickness did not differ between groups in any region. A model that included language‐related fMRI activations within the superior temporal gyrus, age at onset, and demographic variables was the most predictive of language impairment (area under the curve = 0.80).
Significance
These findings demonstrate a unique imaging signature associated with a language‐impaired phenotype in TLE, characterized by functional and microstructural alterations within the language network. Reduced left superior temporal activation combined with compromise to language association tracts underlies this phenotype, extending our previous work on cognitive phenotypes that could have implications for treatment‐planning or cognitive progression in TLE.
Abstract We investigated the relationship between regional atrophy rates and 2-year cognitive decline in a large cohort of patients with mild cognitive impairment (MCI; n = 103) and healthy controls ...( n = 90). Longitudinal magnetic resonance image (MRI) scans were analyzed using high-throughput image analysis procedures. Atrophy rates were derived by calculating percent cortical volume loss between baseline and 24 month scans. Stepwise regressions were performed to investigate the contribution of atrophy rates to language, memory, and executive functioning decline, controlling for age, gender, baseline performances, and disease progression. In MCI, left temporal lobe atrophy rates were associated with naming decline, whereas bilateral temporal, left frontal, and left anterior cingulate atrophy rates were associated with semantic fluency decline. Left entorhinal atrophy rate was associated with memory decline and bilateral frontal atrophy rates were associated with executive function decline. These data provide evidence that regional atrophy rates in MCI contribute to domain-specific cognitive decline, which appears to be partially independent of disease progression. MRI measures of regional atrophy can provide valuable information for understanding the neural basis of cognitive impairment in MCI.
•The amygdala is critical to emotional processing, fear recognition, and memory.•We measured amygdala volumes in brain tumor patients treated with radiation (RT).•RT dose-dependent amygdala atrophy ...was observed at 1 year after treatment.•Amygdala atrophy after brain RT may contribute to neuropsychological deficits.
The amygdalae are deep brain nuclei critical to emotional processing and the creation and storage of memory. It is not known whether the amygdalae are affected by brain radiotherapy (RT). We sought to quantify dose-dependent amygdala change one year after brain RT.
52 patients with primary brain tumors were retrospectively identified. Study patients underwent high-resolution, volumetric magnetic resonance imaging before RT and 1 year afterward. Images were processed using FDA-cleared software for automated segmentation of amygdala volume. Tumor, surgical changes, and segmentation errors were manually censored. Mean amygdala RT dose was tested for correlation with amygdala volume change 1 year after RT via the Pearson correlation coefficient. A linear mixed-effects model was constructed to evaluate potential predictors of amygdala volume change, including age, tumor hemisphere, sex, seizure history, and bevacizumab treatment during the study period. As 51 of 52 patients received chemotherapy, possible chemotherapy effects could not be studied. A two-tailed p-value <0.05 was considered statistically significant.
Mean amygdala RT dose (r = −0.28, p = 0.01) was significantly correlated with volume loss. On multivariable analysis, the only significant predictor of amygdala atrophy was radiation dose. The final linear mixed-effects model estimated amygdala volume loss of 0.17% for every 1 Gy increase in mean amygdala RT dose (p = 0.008).
The amygdala demonstrates dose-dependent atrophy one year after radiotherapy for brain tumors. Amygdala atrophy may mediate neuropsychological effects seen after brain RT.
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