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.

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.

Magnetic resonance evidence of increased iron content in subcortical brain regions in asymptomatic Alzheimer's disease.

While iron over-accumulation has been reported in late stage Alzheimer's disease (AD), whether this occurs early in the asymptomatic stage of AD remains unknown. We aimed to assess brain iron levels in asymptomatic AD using quantitative MR relaxometry of effective transverse relaxation rate (R2*) and longitudinal relaxation rate (R1), and recruited 118 participants comprised of three groups including healthy young participants, and cognitively normal older individuals without or with positive AD biomarkers based on cerebrospinal fluid (CSF) proteomics analysis. Compared with the healthy young group, increased R2* was found in widespread cortical and subcortical regions in the older groups. Further, significantly higher levels of R2* were found in the cognitively normal older subjects with positive CSF AD biomarker (i.e., asymptomatic AD) compared with those with negative AD biomarker in subcortical regions including the left and right caudate, left and right putamen, and left and right globus pallidus (p < .05 for all regions), suggesting increased iron content in these regions. Subcortical R2* of some regions was found to significantly correlate with CSF AD biomarkers and neuropsychological assessments of visuospatial functions. In conclusion, R2* could be a valuable biomarker for studying early pathophysiological changes in AD.

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.

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.

Rationale and Design of the National Neuropsychology Network.

OBJECTIVE: The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology's transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency. METHOD: The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures. RESULTS: NNN is acquiring item-level data from 500-10,000 patients across 47 widely used Neuropsychology (NP) tests and sharing these data via the NIMH Data Archive. Modern psychometric methods (e.g., item response theory) will specify the constructs measured by different tests and determine their positive/negative predictive power regarding diagnostic outcomes and relationships to other clinical, historical, and demographic factors. The Structured History Protocol for NP (SHiP-NP) helps standardize acquisition of relevant history and self-report data. CONCLUSIONS: NNN is a proof-of-principle collaboration: by addressing logistical challenges, NNN aims to engage other clinics to create a national and ultimately an international network. The mature NNN will provide mechanisms for data aggregation enabling shared analysis and collaborative research. NNN promises ultimately to enable robust diagnostic inferences about neuropsychological test patterns and to promote the validation of novel adaptive assessment strategies that will be more efficient, more precise, and more sensitive to clinical contexts and individual/cultural differences.

Depression and Anxiety in Adult Persons With Epilepsy and Their Caregivers: A Survey-Based Study at a Tertiary Care Center.

ABSTRACT: This study evaluated the rates of depression and anxiety and their determinants in adult persons with epilepsy and their caregivers. Both completed surveys about demographic, disease-related, and psychosocial characteristics. One hundred patients and caregivers participated. A mood disorder was present in 89% of patients and 56% of caregivers. In the univariate analysis, the presence of mood disorder in the patient was associated with being unmarried, unemployed, frequent hospitalizations, side effects from polypharmacy, patient stigma, patient quality of life, caregiver anxiety, and caregiver burden. In the multivariate analysis, medication side effects sustained as an important determinant. In the univariate analysis, the presence of mood disorder in the caregiver was associated with seizure frequency, patient anxiety, patient quality of life, caregiver stigma, and caregiver burden. In the multivariate analysis, patient anxiety level and caregiver burden sustained as important determinants. Adult persons with epilepsy and their caregivers experience high rates of mood disorders, explained by certain clinical factors.

Mood and quality of life in patients treated with brain-responsive neurostimulation: The value of earlier intervention.

OBJECTIVE: To establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention. METHODS: Data were retrospectively analyzed from prospective clinical trials of a direct brain-responsive neurostimulator (RNS® System) for treatment of adults with medically intractable focal-onset epilepsy. Participants completed the Quality of Life in Epilepsy Inventory (QOLIE-31) yearly through 9 years of follow-up and the Beck Depression Inventory-II (BDI-II) through 2 years of follow-up. Changes in each assessment after treatment with responsive neurostimulation were calculated for patients who began treatment within 10 years of seizure onset (early) and those who began treatment 20 years or more after seizure onset (late). RESULTS: The median duration of epilepsy was 18.3 years at enrollment. At 9 years, both the early (N = 51) and late (N = 109) treatment groups experienced similar and significant reductions in the frequency of disabling seizures (73.4% and 77.8%, respectively). The early treatment patients had significant improvements in QoL and mood. However, the late treatment patients not only failed to show these improvements but also declined in the emotional QoL subscale. CONCLUSIONS: Patients treated with brain-responsive neurostimulation earlier in the course of their epilepsy show significant improvements in multiple domains of QoL and mood that are not observed in patients treated later in the course of their epilepsy despite similar efficacy in seizure reduction. Even with similar and substantial reductions in seizure frequency, the comorbidities of uncontrolled epilepsy may be less responsive to treatment when too many years have passed. The results of this study suggest that, as with resective and ablative surgery, treatment with brain-responsive neurostimulation should be delivered as early as possible in the course of medically resistant epilepsy to maximize the opportunity for improvements in mood and QoL.

Vinpocetine, cognition, and epilepsy.

OBJECTIVE: Vinpocetine has been shown to enhance memory in animal models, with possible cognitive benefit in humans. The present study sought to demonstrate if vinpocetine can enhance cognition in healthy volunteers or patients with epilepsy. In addition, we compare blood levels of vinpocetine and its active metabolite (apovincaminic acid; AVA) in humans and animals to further characterize factors related to possible therapeutic benefit. METHODS: The cognitive effects of vinpocetine were assessed in healthy adult volunteers (n = 8) using a double-blind, randomized, crossover design at single doses (placebo, 10, 20, and 60 mg oral). Cognitive effects of vinpocetine in patients with focal epilepsy (n = 8) were tested using a double-blind, randomized, crossover design at single doses (placebo, 20 mg oral) followed by one-month open label at 20 mg oral three times a day. The neuropsychological battery included both computerized and non-computerized tests. Levels of vinpocetine and AVA in the human studies were compared to levels in 45 mice across time dosed at 5-20 mg/kg intraperitoneal of vinpocetine. RESULTS: No significant cognitive benefits were seen in healthy volunteers or patients with epilepsy. No appreciable side effects occurred. Vinpocetine and AVA levels were lower in humans than animals. CONCLUSIONS: Vinpocetine was well tolerated, but was not associated with positive cognitive effects. However, blood levels obtained in humans were substantially less than levels in animals obtained from dosages known to be effective in one model. This suggests that higher dosages are needed in humans to assess vinpocetine's cognitive efficacy.

Folate fortification of food: Insufficient for women with epilepsy.

OBJECTIVE: Folic acid supplementation during the periconceptual period has been shown to improve cognitive outcomes in children of women with epilepsy taking anti-seizure medications (ASMs). The dose of folic acid necessary to provide positive cognitive outcomes is unclear. In many countries including the United States, food is fortified with folic acid, but no data exist on how food fortification may affect cognition in children with fetal-ASM exposure. This study evaluated the effect of dietary folate from natural folates plus folic acid fortification, separate from folic acid vitamin supplements, on age-6 year IQ in children with fetal-ASM exposure. METHODS: Data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study were retrospectively analyzed for this investigation. Assessment of nutrient intake was conducted using the Block Food Frequency Questionnaire-98. The primary outcome of the present study was to assess association of maternal prepregnancy nutrient levels to child age-6 IQ. RESULTS: Folate from food alone without supplement was not associated with improvement of age-6 IQ in children with fetal ASM exposure (95% CI: -11.7-2.3, p = 0.187). Periconceptual folate supplement use was associated with a 10.1-point higher age-6 IQ (95% CI: 5.2-15.0, p < .001). Total combined folate from food plus supplement also showed that higher intake of folate was associated with higher age-6 IQ (Coefficient: 4.5, 95% CI: 2.0-6.9, p < .001). Six other nutrients from food and supplements were analyzed (Vitamin C, Vitamin D, Vitamin E, Omega 3, Gamma Tocopherol, and Vitamin B12) and had no significant association with age 6-IQ. SIGNIFICANCE: Dietary content of folate, even in a country where food is fortified with folic acid, is not sufficient to provide improved cognitive outcomes for children of women taking ASMs during pregnancy. Folate supplementation is needed for significant improvement in cognitive outcomes, specifically age-6 IQ.

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

Subjective Memory Complaints in White and African American Participants.

OBJECTIVE: Subjective memory complaints (SMCs) are associated with mild cognitive impairment and dementia but are understudied in African Americans (AAs). We compared SMC endorsement in white and AA participants and evaluated predictors of diagnostic progression. METHODS: Initial visit variables, including SMC and memory performance, were compared within a cognitively normal race-matched sample of white and AA participants (Ntotal = 912; 456each race) to assess the presence and predictors of SMC, the predictors of future diagnostic progression, and the change in memory performance over time. RESULTS: More white (32.9%) than AA (24.3%) participants reported SMC (P < .01, ϕ = -.10). Subjective memory complaint was predicted by memory performance (B = -0.03, standard error [SE] = 0.013, odds ratio [OR] = .968, P < .05) and race (B = -0.99, SE = 0.080, OR = .373, P < .001). Subjective memory complaints and memory performance were associated with progression, χ2 (3, n = 912) = 102.37, P < .001. African American race (-2.05 ± 0.24 SE) and SMC (-0.45 ± 0.21 SE) were associated with worse memory performance at baseline and over time, χ2(3) = 13.54, P < .01. CONCLUSIONS: In contrast to previous research, our study found that SMC is associated with diagnostic progression and objective memory declines in both white and AA participants.

Stigma in psychogenic nonepileptic seizures.

OBJECTIVE: There is scarce literature on stigma in families living with psychogenic nonepileptic seizures (PNES). Using a cohort of patients with epileptic seizures (ES) and their caregivers as controls, we aimed to quantify the level of patient and caregiver stigma in PNES and identify associations of patient and caregiver characteristics with it. METHODS: Patients with PNES and ES and their caregivers completed surveys about demographic, clinical, and psychosocial characteristics. Multivariate regression analysis was used to identify correlates of patient and caregiver stigma. RESULTS: Forty-three patients with PNES and 165 patients with ES were recruited. Compared with patients with ES, patients with PNES had shorter disease duration, higher seizure frequency, normal diagnostic data, poorer psychosocial health, and fewer antiseizure medications (ASMs). A total of 76.5% of patients with PNES and 59.5% of patients with ES felt stigmatized. Patient stigma level was higher in patients with PNES compared with those with ES, and it was negatively associated with patient quality of life (QOL). Additionally, 28 caregivers of patients with PNES and 99 caregivers of patients with ES were recruited. There were no significant demographic, caregiving, or psychosocial differences between the two caregiver cohorts. Seventy-two percent of caregivers of patients with PNES and 47% of caregivers of patients with ES felt stigmatized. Caregiver stigma level was also higher in caregivers of patients with PNES compared with caregivers of patients with ES, and it was negatively associated with patient QOL and positively associated with patient and caregiver anxiety. CONCLUSION: Compared with those with ES, patients and caregivers living with PNES experience stigma more frequently and to a higher extent. Patient QOL emerges as a consistent correlate of that stigma.

Differential antiseizure medication sensitivity of the Affective Reactivity Index: A randomized controlled trial in new-onset pediatric focal epilepsy.

BACKGROUND: Irritability is a adverse effect of many antiseizure medications (ASMs), but there are no validated measures currently available to characterize this behavioral risk. We examined both child and parent/guardian versions of the Affective Reactivity Index (ARI), a validated measure developed for application in adolescent psychiatry, to determine its sensitivity to ASM-related irritability. We hypothesized irritability increases associated with levetiracetam (LEV) but not lamotrigine (LTG) or oxcarbazepine (OXC). METHOD: The ARI was administered to 71 child and parent/guardian pairs randomized to one of three common ASMs (LEV, LTG, OXC) used to treat new-onset focal (localization-related) epilepsy. Subjects were recruited as part of a prospective multicenter, randomized, open-label, parallel group design. The ARI was administered at baseline prior to treatment initiation and again at 3 months after ASM initiation. RESULTS: There was a significant increase in ARI ratings for both child and parent/guardian ratings for LEV but not LTG or OXC when assessed 3 months after treatment initiation. When examined on the individual subject level using a criterion of at least a 3-point ARI increase, there was an increase associated with LEV for child ratings but not parent/guardian scores. CONCLUSION: Both child and parent/guardian versions of the ARI appear sensitive to medication-induced irritability associated with LEV on both the group and individual levels. The findings extend the applicability of ARI from characterizing the presence of clinical irritability as a psychiatric diagnostic feature to a more modifiable aspect of behavior change related to medication management and support its use in clinical trial applications.

Changes in description naming for common and proper nouns after left anterior temporal lobectomy.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.

Rationale and Design of the Emory Healthy Aging and Emory Healthy Brain Studies.

Understanding the relationships between health and aging is essential for delaying morbidity and maximizing independence in aging populations as life expectancies increase. Loss of cognitive function is a feared age-associated condition and growing public health concern. Alzheimer's disease (AD), the most common cause of dementia, has no curative therapies. Characterizing the relationships between risk factors, biomarkers, and AD progression is critical for the development of effective disease prediction, clinical intervention, and ultimately, disease prevention. The Emory Healthy Aging Study (EHAS) and the Emory Healthy Brain Study (EHBS), which is nested within EHAS, aim to further the understanding of healthy aging and the pathogenesis of age-related illnesses in well-characterized, community-based prospective cohorts and to identify biomarkers for the earliest manifestations of AD for the facilitation of preventative interventions. The EHAS is an innovative, longitudinal, web-based study enrolling English-speaking adults in the U.S. who agree to be contacted for future studies. Using validated instruments, the annual questionnaire enquires about demographics, socioeconomics, self-reported cognitive function, personal and family medical history, lifestyle, and psychosocial factors. Cognitive assessments are also obtained using an ambulatory device. Nested within EHAS, the EHBS is enrolling up to 2,500 EHAS participants, 50-75 years old, who do not have a diagnosis of AD, mild cognitive impairment, or any other memory disorder. EHBS in-person, biennial study visits, include neuropsychological testing, cardiovascular measures, retinal and brain imaging, biospecimen collection (blood, cerebrospinal fluid, gut microbiome), and other assessments. Since spring 2016, EHAS and EHBS have enrolled 12,500 and 863 participants with completed baseline assessments, respectively. Data and biospecimens from EHBS participants will support a broad range of AD biomarker discovery efforts, and follow-up of EHAS participants will enable assessment of self-reported cognitive trajectories and accumulation of incident cases of a variety of health conditions. The EHAS design supports the interval deployment of new study instruments and targeted sampling for ancillary studies. This project will increase our knowledge about healthy aging, improve our understanding of risk factors for cognitive impairment and dementias, support development of biomarkers, and facilitate studies of age-associated disorders including AD.

Comparative neuropsychological effects of carbamazepine and eslicarbazepine acetate.

People with epilepsy are at increased risk for neuropsychological dysfunction due to multiple factors, of which the most amendable are antiseizure medications (ASMs). Antiseizure medication effectiveness is frequently determined by tolerability. In this study, we compared the neuropsychological effects of eslicarbazepine acetate (ESL) and carbamazepine immediate-release (CBZ) using a randomized, double-blind, crossover design in healthy volunteers with a 2-week titration and 4-week maintenance phase in each treatment arm (CBZ = 400 mg BID and ESL = 800 mg qAM). Neuropsychological testing was performed at the initial visit, repeated at 1st baseline nondrug condition, end treatment #1, 2nd nondrug condition one month after treatment #1, end treatment #2, and 3rd nondrug condition one month after treatment #2. Neuropsychological testing was conducted 2 h after morning dose and included computer (i.e., dual task test, selective attention test, symbol digit, verbal memory, visuospatial memory, and 1- & 2-back continuous performance) and noncomputer tasks (i.e., Medical College of Georgia (MCG) paragraph memory, Stroop, Symbol Digit Modalities Test, Profile of Mood States). z-Scores calculated from nondrug conditions were used to compare ESL and CBZ for the 23 completers. Follow-up analyses included individual test scores and distribution of individual raw means. Mean blood levels on test day were CBZ = 8.9 µg/ml and ESL = 15.3 µg/ml. Omnibus z-score was significantly better for ESL (p = .0001). For individual measures, executive function and selective attention tests were statistically significantly better for ESL. Individual test raw means favored ESL over CBZ on 22 of 30 measures (p = .016, 2-tailed sign test). Eslicarbazepine acetate demonstrated less adverse neuropsychological effects than CBZ.

Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study.

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.

Incremental Validity of Montreal Cognitive Assessment Index Scores in Mild Cognitive Impairment and Alzheimer Disease.

BACKGROUND/AIMS: The aim of this paper was to evaluate the incremental validity of the Montreal Cognitive Assessment (MoCA) index scores and the MoCA total score in differentiating individuals with normal cognition versus mild cognitive impairment (MCI) or Alzheimer disease (AD). METHODS: Effect sizes were calculated for Alzheimer's Disease Neuroimaging Initiative research participants with normal cognition (n = 295), MCI (n = 471), or AD (n = 150). RESULTS: Effect sizes for the total score were large (> 0.80) and exceeded the index scores in differentiating those with MCI versus normal cognition, MCI versus AD, and AD versus normal cognition. A combined score incorporating the Memory, Executive, and Orientation indexes also improved incremental validity for all 3 group comparisons. CONCLUSION: Administration of the entire MoCA is more informative than the index scores, especially in distinguishing normal cognition versus MCI. A combined score has stronger incremental validity than the individual index scores.