Health-related quality of life in adults with drug-resistant focal epilepsy treated with modified Atkins diet in a randomized clinical trial.

Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts patients' health-related quality of life (HRQOL). In a randomized controlled design, we compared the change in self-reported HRQOL among adults with difficult-to-treat epilepsy after a 12-week diet intervention. Thirty-nine patients with drug-resistant focal epilepsy (age = 16-65 years) were randomized to eat a modified Atkins diet with maximum 16 g of carbohydrate per day (diet group, n = 19) or to continue eating habitual diet (control group, n = 20). No changes to the other epilepsy treatments were allowed. Patient-reported HRQOL was assessed with the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). The diet group experienced a statistically significant improvement in mean total score of QOLIE-89 of 10 points compared to controls (p = .002). Moreover, although not statistically significant when using a cutoff of 50% seizure reduction, our data suggest an association between diet-induced reduction in seizure frequency and improvement in HRQOL. The improvement in HRQOL was not associated with diet-induced weight reduction.

Cognitive change after DBS in refractory epilepsy: A randomized-controlled trial.

OBJECTIVES: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) reduces seizure frequency in patients with refractory epilepsy. There are, however, few studies on treatment-related changes in cognitive functions. The main objective of this study was to investigate cognitive changes in patients receiving ANT-DBS. We also explored whether possible effects were related to stimulation duration and whether change in seizure frequency was associated with cognitive changes. MATERIALS AND METHODS: Bilateral ANT electrodes were implanted in 18 patients with refractory epilepsy, aged 18-52 years. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the following 6-month open phase, both groups received stimulation. Neuropsychological assessments were conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). RESULTS: Groupwise comparisons across the three time points revealed changes in performance in two of 22 cognitive test scores: motor speed and sustained attention. We found no significant group differences in cognitive change from T1 to T2. Patients reported fewer symptoms of executive dysfunction after 12 months of stimulation. Patients showing significant improvement in seizure frequency had better performance in a measure of verbal learning. CONCLUSION: Our results indicate that ANT-DBS has very limited effects on cognitive functioning, as measured by formal tests after 6- or 12-month stimulation. ANT-DBS may have a positive influence on executive function. Our findings provide limited support for an association between change in seizure frequency and cognitive functioning.

The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance.

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment.

Parent ratings of executive function in young preschool children with symptoms of attention-deficit/-hyperactivity disorder.

BACKGROUND: Recent research has demonstrated that deficits in basic, self-regulatory processes, or executive function (EF), may be related to symptoms of attention-deficit/hyperactivity disorder (ADHD) already during the preschool period. As the majority of studies investigating these relations in young children have been based primarily on clinically administered tests, it is not clear how early symptoms of ADHD may be related to observations of EF in an everyday context. The preschool version of the Behavior Rating Inventory of Executive Function (BRIEF-P) was developed to provide information about EF through observable, behavioral manifestations of self-regulation, and is the most commonly used rating scale for EF assessment in children. METHODS: Relations between symptoms of ADHD reported in the Preschool Age Psychiatric Assessment interview (PAPA), and EF as measured by the BRIEF-P (parent form), were investigated in a large, nonreferred sample of preschool children (37-47 months, n = 1134) recruited from the Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of Public Health. The inventory's discriminative ability was examined in a subsample consisting of children who met the diagnostic criteria for either ADHD, oppositional defiant disorder (ODD) or anxiety disorder, and typically developing controls (n = 308). The four groups were also compared with regard to patterns of EF difficulties reported in the BRIEF-P. RESULTS: Of the five BRIEF-P subscales, Inhibit and Working Memory were the two most closely related to ADHD symptoms, together explaining 38.5% of the variance in PAPA symptom ratings. Based on their scores on the Inhibit and Working Memory subscales (combined), 86.4% of the children in the ADHD and TD groups were correctly classified. ADHD symptoms were associated with more severe difficulties across EF domains, and a different EF profile in comparison to children with other symptoms (anxiety, ODD) and to typically developing controls. CONCLUSIONS: Early symptoms of ADHD were linked to parent-reported difficulties primarily within inhibition and working memory, suggesting that deficiencies within these two EF domains characterize early forms of ADHD. Our findings support the clinical utility of the BRIEF-P as a measure of EF in young preschool children with symptoms of ADHD.

Does IQ influence associations between ADHD symptoms and other cognitive functions in young preschoolers?

BACKGROUND: Working memory, inhibition, and expressive language are often impaired in ADHD and many children with ADHD have lower IQ-scores than typically developing children. The aim of this study was to test whether IQ-score influences associations between ADHD symptoms and verbal and nonverbal working memory, inhibition, and expressive language, respectively, in a nonclinical sample of preschool children. METHODS: In all, 1181 children recruited from the Norwegian Mother and Child Cohort Study were clinically assessed at the age of 36 to 46 months. IQ-score and working memory were assessed with subtasks from the Stanford Binet test battery, expressive language was reported by preschool teachers (Child Development Inventory), response inhibition was assessed with a subtask from the NEPSY test, and ADHD symptoms were assessed by parent interview (Preschool Age Psychiatric Assessment). RESULTS: The results showed an interaction between ADHD symptoms and IQ-score on teacher-reported expressive language. In children with below median IQ-score, a larger number of ADHD symptoms were more likely to be accompanied by reports of lower expressive language skills, while the level of ADHD symptoms exerted a smaller effect on reported language skills in children with above median IQ-score. The associations between ADHD symptoms and working memory and response inhibition, respectively, were not influenced by IQ-score. CONCLUSIONS: Level of IQ-score affected the relation between ADHD symptoms and teacher-reported expressive language, whereas associations between ADHD symptoms and working memory and response inhibition, respectively, were significant and of similar sizes regardless of IQ-score. Thus, in preschoolers, working memory and response inhibition should be considered during an ADHD assessment regardless of IQ-score, while language skills of young children are especially important to consider when IQ-scores are average or low.

Factor structure of the Behavior Rating Inventory of Executive Functions (BRIEF-P) at age three years.

The preschool period is an important developmental period for the emergence of cognitive self-regulatory skills or executive functions (EF). To date, evidence regarding the structure of EF in preschool children has supported both unitary and multicomponent models. The aim of the present study was to test the factor structure of early EF as measured by the Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P). BRIEF-P consists of five subscales and three broader indexes, hypothesized to tap into different subcomponents of EF. Parent ratings of EF from a nonreferred sample of children recruited from the Norwegian Mother and Child Cohort Study (N = 1134; age range 37-47 months) were subjected to confirmatory factor analyses (CFA). Three theoretically derived models were assessed; the second-order three-factor model originally proposed by the BRIEF-P authors, a "true" first-order one-factor model and a second-order one-factor model. CFA fit statistics supported the original three-factor solution. However, the difference in fit was marginal between this model and the second-order one-factor model. A follow-up exploratory factor analysis (EFA) supported the existence of several factors underlying EF in early preschool years, with a considerable overlap with the five BRIEF-P subscales. Our results suggest that some differentiation in EF has taken place at age 3 years, which is reflected in behavior ratings. The internal consistency of the BRIEF-P five clinical subscales is supported. Subscale interrelations may, however, differ at this age from those observed in the preschool group as a whole.

The influence of maternal dietary exposure to dioxins and PCBs during pregnancy on ADHD symptoms and cognitive functions in Norwegian preschool children.

BACKGROUND: Polychlorinated dibenzo-p-dioxins/dibenzofurans (dioxins) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with potentially adverse impact on child neurodevelopment. Whether the potential detrimental effects of dioxins and PCBs on neurodevelopment are of specific or unspecific character is not clear. OBJECTIVES: The purpose of the current study was to examine the influence of maternal dietary exposure to dioxins and PCBs on ADHD symptoms and cognitive functioning in preschoolers. We aimed to investigate a range of functions, in particular IQ, expressive language, and executive functions. MATERIAL AND METHODS: This study includes n=1024 children enrolled in a longitudinal prospective study of ADHD (the ADHD Study), with participants recruited from The Norwegian Mother and Child Cohort Study (MoBa). Boys and girls aged 3.5years participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview (PAPA), Stanford-Binet 5th revision (SB-5), Child Development Inventory (CDI), and Behavior Rating Inventory of Executive Function, Preschool version (BRIEF-P). Maternal dietary exposure to dioxins and PCBs was estimated based on a validated food frequency questionnaire (FFQ) answered mid-pregnancy and a database of dioxin and PCB concentrations in Norwegian foods. Exposure to dioxins and dioxin-like PCBs (dl-compounds) was expressed in total toxic equivalents (TEQ), and PCB-153 was used as marker for non-dioxin-like PCBs (ndl-PCBs). Generalized linear and additive models adjusted for confounders were used to examine exposure-outcome associations. RESULTS: Exposure to PCB-153 or dl-compound was not significantly associated with any of the outcome measures when analyses were performed for boys and girls together. After stratifying by sex, adjusted analyses indicated a small inverse association with language in girls. An increase in the exposure variables of 1 SD was associated with a reduction in language score of -0.2 [CI -0.4, -0.1] for PCB-153 and -0.2 [CI -0.5, -0.1] for dl-compounds in girls. For boys, exposure to PCB-153 or dl-compounds was not associated with language skills. The difference between sex-specific associations was not statistically significant (p-value=0.13). No sex-specific effects were observed for ADHD-symptoms, IQ scores, or executive functions. CONCLUSIONS: We found no indications that variation in current low-level exposure to PCB-153 or dl-compounds in Norway is associated with variation ADHD-symptoms, verbal/non-verbal IQ, or executive functions including working memory in preschoolers. However, our findings indicated that maternal dietary exposure to PCB-153 or dl-compounds during pregnancy was significantly associated with poorer expressive language skills in preschool girls, although the sex-specific associations were not significantly different.

Inhibition and working memory in young preschool children with symptoms of ADHD and/or oppositional-defiant disorder.

BACKGROUND: Early symptoms of attention deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD) are associated with deficits in cognitive self-regulatory processes or executive functions (EF)s. However, the hypothesis that neurocognitive deficits underlying the two disorders are already evident during early preschool years still has limited empirical support. The present study investigated associations between symptoms of ADHD and/or ODD and two core EFs, inhibition and working memory, in a large nonclinical sample of 3-year old children. METHOD: Participants were 1045 children (554 boys, age 37-47 months), recruited from the population based Norwegian Mother and Child Cohort Study (MoBa). Relations between behavioral symptoms and measures of inhibition and working memory were studied both categorically and dimensionally. RESULTS: Children with co-occurring symptoms of ADHD and ODD performed at a significantly lower level than typically developing children in 4 out of 5 EF measures. Symptoms of ADHD, both alone and in combination with ODD, were associated with reduced performance on tests of inhibition in the group comparisons. Dimensional analyses showed that performance within both EF domains contributed to variance primarily in ADHD symptom load. The associations between test results and behavioral symptoms remained significant after gender and verbal skills had been controlled. CONCLUSION: Young preschoolers show the same pattern of relations between EF and behavioral symptoms of ADHD and/or ODD as previously described in older children diagnosed with ADHD and/or ODD. Effect sizes were generally small, indicating that measures of EF have limited clinical utility at this stage in development.