Comparison of minimally invasive to standard temporal lobectomy approaches to epilepsy surgery: Seizure relief and visual confrontation naming outcomes.

The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.

Selective Posterior Cerebral Artery Wada Better Predicts Good Memory and Naming Outcomes Following Selective Stereotactic Thermal Ablation for Medial Temporal Lobe Epilepsy Than Internal Carotid Artery Wada.

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH). We included all patients being considered for SLAH who underwent both ICA-Wada and PCA-Wada at a single institution. Memory and confrontation naming assessments were conducted using standardized neuropsychological tests to assess pre- to post-surgical changes in cognitive performance. Of 13 patients who initially failed the ICA-Wada, only one patient subsequently failed the PCA-Wada (p=0.003, two-sided binomial test with p 0 =0.5) demonstrating that these tests assess different brain regions or networks. PCA-Wada had a high negative predictive value for the safety of SLAH, compared to ICA-Wada, as none of the patients who underwent SLAH after passing the PCA-Wada experienced catastrophic memory decline (0 of 9 subjects, p <.004, two-sided binomial test with p 0 =0.5), and all experienced a good cognitive outcome. In contrast, the single patient who received a left anterior temporal lobectomy after failed ICA- and passed PCA-Wada experienced a persistent, near catastrophic memory decline. On confrontation naming, few patients exhibited disturbance during the PCA-Wada. Following surgery, SLAH patients showed no naming decline, while open resection patients, whose surgeries all included ipsilateral temporal lobe neocortex, experienced significant naming difficulties (Fisher's exact test, p <.05). These findings demonstrate that (1) failing the ICA-Wada falsely predicts memory decline following SLAH, (2) PCA-Wada better predicts good memory outcomes of SLAH for MTLE, and (3) the MTL brain structures affected by both PCA-Wada and SLAH are not directly involved in language processing.

The Montreal Cognitive Assessment: Norms and Reliable Change Indices for Standard and MoCA-22 Administrations.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is among the most frequently administered cognitive screening tests, yet demographically diverse normative data are needed for repeated administrations. METHOD: Data were obtained from 18,410 participants using the National Alzheimer's Coordinating Center Uniform Data Set. We developed regression-based norms using Tobit regression to account for ceiling effects, explored test-retest reliability of total scores and by domain stratified by age and diagnosis with Cronbach's alpha, and reported the cumulative change frequencies for individuals with serial MoCA administrations to gage expected change. RESULTS: Strong ceiling effects and negative skew were observed at the total score, domain, and item levels for the cognitively normal group, and performances became more normally distributed as the degree of cognitive impairment increased. In regression models, years of education was associated with higher MoCA scores, whereas older age, male sex, Black and American Indian or Alaska Native race, and Hispanic ethnicity were associated with lower predicted scores. Temporal stability was adequate and good at the total score level for the cognitively normal and cognitive disorders groups, respectively, but fell short of reliability standards at the domain level. CONCLUSIONS: MoCA total scores are adequately reproducible among those with cognitive diagnoses, but domain scores are unstable. Robust regression-based norms should be used to adjust for demographic performance differences, and the limited reliability, along with the ceiling effects and negative skew, should be considered when interpreting MoCA scores.

Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy.

Importance: The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. Objective: To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. Design, Setting, and Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. Exposures: Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. Main Outcomes and Measures: The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. Results: Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. Conclusions and Relevance: This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.

Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study.

BACKGROUND: The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. FINDINGS: Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102·7, 95% CI 101·4 to 103·9) versus those without epilepsy (n=87; 102·3, 99·8 to 104·7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate -2·9, 95% CI -6·7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. INTERPRETATION: We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development.

Depression and anxiety in caregivers of patients with functional seizures.

OBJECTIVE: Contrary to patients, the psychological impact of functional seizures to caregivers has not been adequately investigated. This study aimed to evaluate the rates and determinants of depression and anxiety in caregivers of patients with functional seizures. METHODS: Patients with functional seizures and their caregivers completed surveys about demographic, disease-related, and psychosocial characteristics. Rates and determinants of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventory scores as dependent variables and patient and caregiver characteristics as independent variables. RESULTS: Twenty-nine patients (76% female, mean age of 37 years) and their caregivers (59% female, mean age of 43 years) were recruited. Symptoms of anxiety and/or depression were present in 96% of patients (96% depression, 92% anxiety) and 59% of caregivers (52% depression, 50% anxiety). Specifically, 31% of caregivers manifested mild depression, 14% moderate depression, and 7% severe depression, whereas 48% were not depressed. Similarly, 14% of caregivers manifested mild anxiety, 29% moderate anxiety, and 7% severe anxiety, whereas 50% were not anxious. Patient and caregiver depression levels strongly correlated (r = .73, p < .0001). The presence of anxiety and depression in the caregiver was associated with male patient gender (p = .02), patient depression level (p = .002), the caregiver being a parent or sibling (p = .02), and caregiver burden (p = .0009). SIGNIFICANCE: Caregivers of patients with functional seizures experience high rates of anxiety and depression, explained by specific demographic and psychosocial factors that could act as intervention targets.

The effect of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes in drug-resistant epilepsy.

OBJECTIVE: The impact of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes has not been extensively evaluated outside of the original clinical trials and post-approval studies. The goal of this study was to ascertain the potential real-world effects of RNS on cognitive, psychiatric, and quality of life (QOL) outcomes in relation to seizure outcomes by examining 50 patients undergoing RNS implantation for drug-resistant epilepsy (DRE). METHODS: We performed a retrospective review of all patients treated at our institution with RNS for DRE with at least 12 months of follow-up. In addition to baseline demographic and disease-related characteristics, we collected cognitive (Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning Index), psychiatric (Beck Depression and Anxiety Inventory Scores), and QOL (QOLIE-31) outcomes at 6 and 12 months after RNS implantation and correlated them with seizure outcomes. RESULTS: Fifty patients (median age 39.5 years, 64% female) were treated with RNS for DRE in our institution from 2005 to 2020. Of the 37 of them who had well-documented pre and post-implantation seizure diaries, the 6-month median seizure frequency reduction was 88%, the response rate (50% or greater seizure frequency reduction) was 78%, and 32% of patients were free of disabling seizures in this timeframe. There was no statistically significant difference at a group level in any of the evaluated cognitive, psychiatric, and QOL outcomes at 6 and 12 months post-implantation compared to the pre-implantation baseline, irrespective of seizure outcomes, although a subset of patients experienced a decline in mood or cognitive variables. SIGNIFICANCE: Responsive neurostimulation does not appear to have a statistically significant negative or positive impact on neuropsychiatric and psychosocial status at the group level. We observed significant variability in outcome, with a minority of patients experiencing worse behavioral outcomes, which seemed related to RNS implantation. Careful outcome monitoring is required to identify the subset of patients experiencing a poor response and to make appropriate adjustments in care.

Predictors of Cognitive Decline in Healthy Middle-Aged Individuals with Asymptomatic Alzheimer's Disease.

Alzheimer's disease (AD) progresses through a lengthy asymptomatic period during which pathological changes accumulate prior to development of clinical symptoms. As disease-modifying treatments are developed, tools to stratify risk of clinical disease will be required to guide their use. In this study, we examine the relationship of AD biomarkers in healthy middle-aged individuals to health history, family history, and neuropsychological measures and identify cerebrospinal fluid (CSF) biomarkers to stratify risk of progression from asymptomatic to symptomatic AD. CSF from cognitively normal (CN) individuals (N=1149) in the Emory Healthy Brain Study were assayed for Aß42, total Tau (tTau), and phospho181-Tau (pTau), and a subset of 134 cognitively normal, but biomarker-positive, individuals were identified with asymptomatic AD (AsymAD) based on a locally-determined cutoff value for ratio of tTau to Aß42. These AsymAD cases were matched for demographic features with 134 biomarker-negative controls (CN/BM-) and compared for differences in medical comorbidities and family history. Dyslipidemia emerged as a distinguishing feature between AsymAD and CN/BM-groups with significant association with personal and family history of dyslipidemia. A weaker relationship was seen with diabetes, but there was no association with hypertension. Examination of the full cohort by median regression revealed a significant relationship of CSF Aß42 (but not tTau or pTau) with dyslipidemia and diabetes. On neuropsychological tests, CSF Aß42 was not correlated with performance on any measures, but tTau and pTau were strongly correlated with visuospatial perception and visual episodic memory. In addition to traditional CSF AD biomarkers, a panel of AD biomarker peptides derived from integrating brain and CSF proteomes were evaluated using machine learning strategies to identify a set of 8 peptides that accurately classified CN/BM- and symptomatic AD CSF samples with AUC of 0.982. Using these 8 peptides in a low dimensional t-distributed Stochastic Neighbor Embedding analysis and k-Nearest Neighbor (k=5) algorithm, AsymAD cases were stratified into "Control-like" and "AD-like" subgroups based on their proximity to CN/BM- or AD CSF profiles. Independent analysis of these cases using a Joint Mutual Information algorithm selected a set of 5 peptides with 81% accuracy in stratifying cases into AD-like and Control-like subgroups. Performance of both sets of peptides was evaluated and validated in an independent data set from the Alzheimer's Disease Neuroimaging Initiative. Based on our findings, we conclude that there is an important role of lipid metabolism in asymptomatic stages of AD. Visuospatial perception and visual episodic memory may be more sensitive than language-based abilities to earliest stages of cognitive decline in AD. Finally, candidate CSF peptides show promise as next generation biomarkers for predicting progression from asymptomatic to symptomatic stages of AD.

The Future of Cognitive Screening in Neurodegenerative Diseases.

Cognitive screening instruments (CSI) have variable sensitivity and specificity to the cognitive changes associated with dementia syndromes, and the most recent systematic review found insufficient evidence to support the benefit of cognitive screening tools in older adults residing within the community. Consequently, there is a critical need to improve CSI methods, which have not yet incorporated advances in psychometrics, neuroscience, and technology. The primary goal of this article is to provide a framework for transitioning from legacy CSIs to advanced dementia screening measurement. In line with ongoing efforts in neuropsychology and the call for next-generation digital assessment for early detection of AD, we propose a psychometrically advanced (including application of item response theory methods), automated selective assessment model that provides a framework to help propel an assessment revolution. Further, we present a three-phase model for modernizing CSIs and discuss critical diversity and inclusion issues, current challenges in differentiating normal from pathological aging, and ethical considerations.

Telehealth equivalence of the Montreal cognitive assessment (MoCA): Results from the Emory healthy brain study (EHBS).

BACKGROUND: We investigated potential differences between in-person cognitive testing and video telehealth administration of the Montreal Cognitive Assessment (MoCA). In addition to the MoCA, the Patient Health Questionnaire-8 (PHQ-8) and Generalized Anxiety Disorder-7 (GAD-7) were administered. METHODS: MoCA scores from participants in the Emory Health Brain Study (EHBS) were contrasted based upon whether they were administered the MoCA in the standard face-to-face (F2F) assessment setting (n = 1205) or using a video telehealth administration (n = 491). All EHBS participants were self-reported to be cognitively normal. RESULTS: MoCA scores did not differ across administration method (F2F MoCA = 26.6, SD = 2.4; telehealth MoCA = 26.5, SD = 2.4). The 95% confidence interval for difference in administration was small (CI = -0.16 to 0.34). When examining MoCA domain scores, administration differences were either associated with no statistically significant effect, or if present due to large sample sizes, were associated with small effects and differences <0.5 point. Telehealth patients reported slightly lower PHQ-8 scores (F2F PHQ-8 = 2.0, SD = 2.5; telehealth PHQ-8 = 1.6, SD = 2.1), although these scores are well within the normal range. No group difference in GAD-7 scores was present (F2F GAD-7 = 1.4, SD = 2.4; telehealth PHQ-8 = 1.4, SD = 2.4). DISCUSSION: This report with its large sample size and between subject cohort provides complementary evidence to smaller test-retest studies, further supporting equivalence of MoCA telehealth testing to F2F MoCA administration. These findings provide additional reassurance that administration mode does not introduce systematic performance differences for MoCA test administration, thereby permitting telehealth MoCA testing to be applied confidently for both clinical and research applications.

Construct identification in the neuropsychological battery: What are we measuring?

OBJECTIVE: Major obstacles to data harmonization in neuropsychology include lack of consensus about what constructs and tests are most important and invariant across healthy and clinical populations. This study addressed these challenges using data from the National Neuropsychology Network (NNN). METHOD: Data were obtained from 5,000 NNN participants and Pearson standardization samples. Analyses included variables from four instruments: Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV); Wechsler Memory Scale, 4th Edition (WMS-IV); California Verbal Learning Test, 3rd Edition (CVLT3); and Delis-Kaplan Executive Function System (D-KEFS). We used confirmatory factor analysis to evaluate models suggested by prior work and examined fit statistics and measurement invariance across samples. We examined relations of factor scores to demographic and clinical characteristics. RESULTS: For each instrument, we identified four first-order and one second-order factor. Optimal models in patients generally paralleled the best-fitting models in the standardization samples, including task-specific factors. Analysis of the NNN data prompted specification of a Recognition-Familiarity factor on the WMS-IV and an Inhibition-Switching factor on the D-KEFS. Analyses showed strong to strict factorial invariance across samples with expected differences in factor means and variances. The Recognition-Familiarity factor correlated with age more strongly in NNN than in the standardization sample. CONCLUSIONS: Factor models derived from healthy groups generally fit well in patients. NNN data helped identify novel Recognition-Familiarity and Inhibition-Switching factors that were also invariant across samples and may be clinically useful. The findings support efforts to identify evidence-based and optimally efficient measurements of neuropsychological constructs that are valid across groups. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Initial results from a multi-center study of adults with temporal lobe epilepsy.

[Correction Notice: An Erratum for this article was reported online in Neuropsychology on Sep 15 2022 (see record 2023-01997-001). In the original article, there was an error in Figure 2. In the box at the top left of the figure, the fourth explanation incorrectly stated, "Generalized impairment = At least one test < -1.0 or -1.5SD in three or more domains." The correct wording is "Generalized impairment = At least two tests < -1.0 or -1.5SD in each of three or more domains." All versions of this article have been corrected.] Objective: To describe the development and application of a consensus-based, empirically driven approach to cognitive diagnostics in epilepsy research-The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) and to assess the ability of the IC-CoDE to produce definable and stable cognitive phenotypes in a large, multi-center temporal lobe epilepsy (TLE) patient sample. METHOD: Neuropsychological data were available for a diverse cohort of 2,485 patients with TLE across seven epilepsy centers. Patterns of impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) using two impairment thresholds (≤1.0 and ≤1.5 standard deviations below the normative mean). Cognitive phenotypes were derived across samples using the IC-CoDE and compared to distributions of phenotypes reported in existing studies. RESULTS: Impairment rates were highest on tests of language, followed by memory, executive functioning, attention/processing speed, and visuospatial ability. Application of the IC-CoDE using varying operational definitions of impairment (≤ 1.0 and ≤ 1.5 SD) produced cognitive phenotypes with the following distribution: cognitively intact (30%-50%), single-domain (26%-29%), bi-domain (14%-19%), and generalized (10%-22%) impairment. Application of the ≤ 1.5 cutoff produced a distribution of phenotypes that was consistent across cohorts and approximated the distribution produced using data-driven approaches in prior studies. CONCLUSIONS: The IC-CoDE is the first iteration of a classification system for harmonizing cognitive diagnostics in epilepsy research that can be applied across neuropsychological tests and TLE cohorts. This proof-of-principle study in TLE offers a promising path for enhancing research collaborations globally and accelerating scientific discoveries in epilepsy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Classification statistics of the Montreal Cognitive Assessment (MoCA): Are we interpreting the MoCA correctly?

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a common cognitive screener for detecting mild cognitive impairment (MCI). However, previously suggested cutoff scores of 26/30 and above is often criticized and lacks racial diversity. The purpose of this study is to investigate the potential influence of race on MoCA classification cutoff score accuracy. METHOD: Data were obtained from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set and yielded 4,758 total participants. Participants were predominately White (82.8%) and female (61.7%) with a mean age of 69.3 years (SD = 10.3) and education level of 16.3 years (SD = 2.6). Based on NACC's classification, participants were either cognitively normal (n = 3,650) or MCI (n = 1,108). RESULTS: Sensitivity and specificity analyses revealed that when using the cutoff score of ≤26/30, the MoCA correctly classified 73.2% of White cognitively normal participants and 83.1% of White MCI participants. In contrast, this criterion correctly classified 40.5% of Black cognitively normal participants and 90.8% of Black MCI participants. Our sample was highly educated; therefore, we did not observe significant differences in scores when accounting for education across race. Classification statistics are presented. CONCLUSIONS: Black participants were misclassified at a higher rate than White participants when applying the ≤26/30 cutoff score. We suggest cutoff scores of ≤25/30 be applied to White persons and ≤22/30 for Black persons. These findings highlight the need for racially stratified population-based norms given the high misclassification of Black participants without such adjustment.

The Rey Auditory Verbal Learning Test: Cross-validation of Mayo Normative Studies (MNS) demographically corrected norms with confidence interval estimates.

OBJECTIVE: The Mayo Normative Studies (MNS) represents a robust dataset that provides demographically corrected norms for the Rey Auditory Verbal Learning Test. We report MNS application to an independent cohort to evaluate whether MNS norms accurately adjust for age, sex, and education differences in subjects from a different geographic region of the country. As secondary goals, we examined item-level patterns, recognition benefit compared to delayed free recall, and derived Auditory Verbal Learning Test (AVLT) confidence intervals (CIs) to facilitate clinical performance characterization. METHOD: Participants from the Emory Healthy Brain Study (463 women, 200 men) who were administered the AVLT were analyzed to demonstrate expected demographic group differences. AVLT scores were transformed using MNS normative correction to characterize the success of MNS demographic adjustment. RESULTS: Expected demographic effects were observed across all primary raw AVLT scores. Depending on sample size, MNS normative adjustment either eliminated or minimized all observed statistically significant AVLT differences. Estimated CIs yielded broad CI ranges exceeding the standard deviation of each measure. The recognition performance benefit across age ranged from 2.7 words (SD = 2.3) in the 50-54-year-old group to 4.7 words (SD = 2.7) in the 70-75-year-old group. CONCLUSIONS: These findings demonstrate generalizability of MNS normative correction to an independent sample from a different geographic region, with demographic adjusted performance differences close to overall performance levels near the expected value of T = 50. A large recognition performance benefit is commonly observed in the normal aging process and by itself does not necessarily suggest a pathological retrieval deficit.

Case study of invalid to valid shift in cognitive performance following successful treatment of psychogenic nonepileptic seizure events.

Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.

Clinical value of the Montreal Cognitive Assessment free recall condition alone versus cued recall and recognition conditions to detect true memory impairment.

The Montreal Cognitive Assessment (MoCA) is widely used as a screener to characterize cognition. Although only the delayed free recall condition is required for administration, performance on the optional cued recall and multiple-choice recognition conditions may improve diagnostic accuracy over free recall alone. Data on 719 individuals with MCI and 601 controls were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The Rey Auditory Verbal Learning Test (AVLT) delayed free recall condition was used as the gold standard of memory status. Participants with T-scores ≤30 (≤2 SDs below the mean) were classified as memory "impaired." Binary logistic regressions assessed if combined MoCA cued recall/recognition predicted impaired delayed recall on the AVLT beyond the contribution of MoCA free recall. Results showed that MoCA free recall predicted AVLT delayed recall, and that the addition of combined MoCA cued recall/recognition improved the ability to detect impaired AVLT recall, with a better overall model fit. The combined MoCA cued recall/recognition score also had higher specificity and likelihood ratios in detecting memory impairment than MoCA free recall, while higher sensitivity values were present for free recall. Thus, the additional administration of the MoCA cued recall and recognition is recommended.

Multimodal magnetic resonance imaging reveals distinct sensitivity of hippocampal subfields in asymptomatic stage of Alzheimer's disease.

While hippocampal atrophy and its regional susceptibility to Alzheimer's disease (AD) are well reported at late stages of AD, studies of the asymptomatic stage of AD are limited but could elucidate early stage pathophysiology as well as provide predictive biomarkers. In this study, we performed multi-modal magnetic resonance imaging (MRI) to estimate morphometry, functional connectivity, and tissue microstructure of hippocampal subfields in cognitively normal adults including those with asymptomatic AD. High-resolution resting-state functional, diffusion and structural MRI, cerebral spinal fluid (CSF), and neuropsychological evaluations were performed in healthy young adults (HY: n = 40) and healthy older adults with negative (HO-: n = 47) and positive (HO+ : n = 25) CSF biomarkers of AD. Morphometry, functional connectivity, and tissue microstructure were estimated from the structural, functional, and diffusion MRI images, respectively. Our results indicated that normal aging affected morphometry, connectivity, and microstructure in all hippocampal subfields, while the subiculum and CA1-3 demonstrated the greatest sensitivity to asymptomatic AD pathology. Tau, rather than amyloid-ß, was closely associated with imaging-derived synaptic and microstructural measures. Microstructural metrics were significantly associated with neuropsychological assessments. These findings suggest that the subiculum and CA1-3 are the most vulnerable in asymptomatic AD and tau level is driving these early changes.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.