Jurgen Lemiere

Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study.

Abstract.ObjectiveObjective information about the onset and progression of cognitive impairment in Huntington’s disease (HD) is very important in the light of appropriate outcome measures when conducting clinical trials. Therefore, we evaluated the progression of cognitive functions in HD patients and asymptomatic carriers of the HD mutation (AC) over a 2.5–year period.We also sought to detect the earliest markers of cognitive impairment in AC.MethodsA prospective study comparing HD patients, clinically asymptomatic HD mutation–carriers (AC) and non–carriers (NC). These groups were examined three times during a period of 2.5 years. At baseline the study sample consisted of 49 subjects. Forty–two subjects (19 HD patients, 12 AC and 11 NC) completed three assessments. A battery of neuropsychological tests measuring intelligence, attention, memory, language, visuospatial perception, and executive functions was performed.ResultsThe performance of HD patients deteriorated on the following cognitive tests: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word, Boston Naming Test (BNT), Object and Space Perception and Trail Making Test–B. Longitudinal comparison of AC and NC revealed that performances on SDMT, Block Span, Digit Span Backwards, Hopkins Verbal Learning Test (learning and delayed recall) and Conditional Associative Learning Test are impaired in AC.ConclusionsTasks measuring mainly attention, object and space perception and executive functions adequately assess the progression of HD disease. Other cognitive functions do not significantly deteriorate. Furthermore, problems in attention, working memory, verbal learning, verbal long–term memory and learning of random associations are the earliest cognitive manifestations in AC.

Longitudinal study evaluating neuropsychological changes in so‐called asymptomatic carriers of the Huntington's disease mutation after 1 year

Objectives– To determine (1) whether the battery of neuropsychological tests was sufficiently sensitive to find differences between symptomatic patients with Huntingtons disease (HD) and clinically asymptomatic individuals carrying the HD gene (AGC) and individuals without the HD gene (NGC) and (2) whether increasing cognitive impairment is found in AGC as compared with NGC. Methods– A case–control, single‐blind study comparing subjects with clinically manifest HD (n=21), AGC (n=12) or NGC (n=11) and a 1‐year follow‐up of AGC and NGC. Genotype for the HD gene was determined by molecular testing. A large battery of neuropsychological tests measuring several cognitive domains was performed. Results– On most neuropsychological tasks, HD patients perform significantly worse than AGC and NGC. At baseline and follow‐up examination, compared with NGC, AGC had lower scores on the symbol digit modalities test. Scores on a block span task declined more rapidly among AGC than among NGC. Conclusion– Cognitive impairments in HD patients are found when compared with clinically asymptomatic individuals carrying the HD mutation. Furthermore, our results suggest that subtle cognitive deficits are present in asymptomatic persons who have inherited the HD gene.

Brain activation to cues predicting inescapable delay in adolescent Attention Deficit/Hyperactivity Disorder: an fMRI pilot study

BACKGROUND The choice of small immediate over large delayed rewards (i.e., impulsive choice) is a signal marker of motivational style in Attention Deficit/Hyperactivity Disorder (ADHD). The delay aversion model proposes that, in part, this is a conditioned delay avoidance response. Here we test the prediction derived from this model that, in ADHD, cues predicting inescapable delay differentially activate brain regions shown previously to be responsive to motivationally salient, negatively valenced environmental events. METHODS Ten adolescents with ADHD and 10 age matched controls performed a simple speeded reaction time task under two conditions. On Escape Delay trials slow responses only were punished by the imposition of post-response delay periods. On No Escape Delay trials post-response delay occurred on all trials irrespective of response speed. Using functional Magnetic Resonance Imaging (fMRI) BOLD responses were acquired to compare anticipatory brain activation following the two cue types. ROI analyses found significant ADHD-related hyperactivation following No Escape compared to Escape Delay trial cues in the insula, amygdala, ventral striatum and orbito-frontal cortex. CONCLUSION The results of this pilot study provide further evidence for the role of altered motivational systems in ADHD and the most direct evidence for a biological basis of delay aversion.

Impact of self-esteem on the relationship between orthodontic treatment need and oral health-related quality of life in 11- to 16-year-old children

The interest in the psychological aspects of orthodontic treatment increases, but a drawback of many studies is that the psychological characteristics of the children themselves are often ignored. One of these psychological attributes is self-esteem (SE), which is a relatively stable personal resource that might moderate the effects of conditions or events. The aim of this study was to investigate whether there is a relationship between orthodontic treatment need and oral health-related quality of life (OHRQoL) and whether this relationship is influenced by SE. This cross-sectional study comprised 223 children (113 boys and 110 girls) between 11 and 16 years of age (mean age 13.2 years), seeking orthodontic treatment. The OHRQoL was scored by the use of the Child Perception Questionnaire (CPQ(11-14)). The Dutch adaptation of the Harters Self-Perception Profile was used to assess SE, and the Index of Orthodontic Treatment Need defined the need for treatment. Spearman correlations, Mann-Whitney U-tests, and regression models were used to analyze the data. There was a significant relationship between orthodontic treatment need and OHRQoL, and between SE and OHRQoL. No evidence was found that SE moderates the relationship between OHRQoL and treatment need.

Neurocognition after paediatric heart surgery: a systematic review and meta-analysis

Children with congenital heart disease (CHD) often experience difficulties in academic and daily functioning, which have been associated with intelligence and neurocognitive skills, including executive functions (EFs), attention and memory. We report the neurocognitive data of children with CHD who were included in the Leuven glucose control trial (LGC trial). Through a systematic review and meta-analysis, we aimed to find which neurocognitive functions are most consistently and prominently affected. 365 children with CHD and 216 healthy control children underwent extensive neurocognitive testing in the LGC trial. A comprehensive search of electronic databases PubMed, EMBASE and Cochrane was conducted for studies measuring intelligence, EFs, attention and memory in children who underwent heart surgery for CHD. Standardised mean differences (SMDs) between the CHD group and a healthy control group were calculated for these neurocognitive functions. LGC trial data were included in the meta-analysis. Twelve studies with a healthy control group were included in the meta-analysis, involving 647 patients with CHD and 633 controls. The CHD group (median age 7.35 years at testing) had worse scores than healthy control children, for all investigated neurocognitive functions. A medium SMD was found for intelligence (SMD=−0.53 (95% CI −0.68 to −0.38), p<0.00001). Alertness, an attentional function, was also consistently poorer in the CHD group. Memory was less affected, while EF had a medium SMD with large heterogeneity. Children with CHD risk displayed lower performance on intelligence and alertness assessment, which may contribute to difficulties in daily life and school. Heterogeneity in neurocognitive assessment and small sizes in most studies limit the interpretation. Trial registration number clinicaltrials.gov Identifier NCT00214916.

Are children with ADHD predominantly inattentive and combined subtypes different in terms of aspects of everyday attention

The validity of the DSM-IV subtypes is a recurring diagnostic debate in attention deficit/hyperactivity disorder (ADHD). Laboratory measures, such as the test of everyday attention for children (TEA-Ch) can help us address this question. TEA-Ch is a test battery covering different aspects of everyday attention relating to selective and sustained attention and attentional control. The aim of the current study was to investigate whether this instrument can differentiate between combined (ADHD-C) and inattentive subtype (ADHD-I) of ADHD. Subjects were recruited from a multidisciplinary ADHD outpatient unit and tested free of medication. Sixty-four children with a diagnosis of ADHD were included (38 with ADHD-C; 26 with ADHD-I). The control group was 76 children recruited from primary and secondary schools. Children with ADHD performed worse than controls on 6 out of 9 TEA-Ch subtests. However a regression analysis revealed that TEA-Ch subtests made only a marginal contribution to the correct classification of ADHD, once the effects of IQ and age are controlled. Confirmatory factor analysis in our ADHD group demonstrated that the three factor structure achieved a poor fit. More detailed analysis suggested that inferior performance on the tasks designed to test vigilance was not the result of deficient-sustained attention. ADHD-C and ADHD-I showed very few differences across tasks. In conclusion, our results provided not much support for the value of the ADHD-C and ADHD-I distinction in predicting difficulties in everyday attention.

No association between the 2D:4D fetal testosterone marker and multidimensional attentional abilities in children with ADHD

Aim  It has been suggested that high levels of prenatal testosterone exposure are implied in the aetiology of attention‐deficit–hyperactivity disorder (ADHD). This study examined the association between the ratio of the length of the second and fourth digits (2D:4D ratio), a marker of fetal testosterone exposure, and the presence of ADHD‐related cognitive and behavioural problems in children with ADHD and in typically developing comparison individuals.

Changes in oral health-related quality of life reports in children during orthodontic treatment and the possible role of self- esteem: a follow-up study

OBJECTIVES As a continuation of a baseline study on oral health-related quality of life (OHRQoL) and the role of self-esteem (SE), the aim of this research is to investigate the changes in OHRQoL reports in children during orthodontic treatment and the influence of SE. SUBJECTS AND METHODS This longitudinal study comprised 109 children (50 boys and 59 girls) aged 11-16 years, all receiving orthodontic treatment. Questionnaires were administered at baseline and at follow-up (1 year after start of orthodontic treatment). OHRQoL was assessed by the child perception questionnaire (CPQ). The Dutch adaptation of the Harters Self-Perception Profile for Adolescents was used to assess SE and the Index of Orthodontic Treatment Need defined the need for treatment. The questionnaires also included questions related to motivation for treatment. Spearman correlations, Wilcoxon signed rank tests and Mann-Whitney U-tests were performed. RESULTS A significant increase in total CPQ score was found during orthodontic treatment. This increase was also significant for the subdomains functional limitations, oral symptoms, and social well-being, whereas for the subdomain emotional well-being a non-significant decrease in CPQ score was found. Children with high SE at baseline showed significantly lower variability in OHRQoL measures at follow-up. CONCLUSIONS OHRQoL deteriorates in children during orthodontic treatment. There is evidence that SE can be a protective factor in OHRQoL during orthodontic treatment.

Child and parental executive functioning in type 1 diabetes: Their unique and interactive role toward treatment adherence and glycemic control

Managing type 1 diabetes (T1D) requires the ability to make complex and critical decisions regarding treatment, to execute complex tasks accurately, and to make adjustments when problems arise. This requires effective neuropsychological competences of patients and their families, especially in the domain of executive functioning (EF): the ability to self‐monitor, plan, solve problems, and set priorities. Previous research focused mainly on child EF, neglecting the impact of parental EF. This study included both mothers and fathers and examined associations between child and parental EF and treatment adherence to T1D in a broad age range of patients.

Chemotherapy-induced neurotoxicity in pediatric solid non-CNS tumor patients: An update on current state of research and recommended future directions.

Neurocognitive sequelae are known to be induced by cranial radiotherapy and central-nervous-system-directed chemotherapy in childhood Acute Lymphoblastic Leukemia (ALL) and brain tumor patients. However, less evidence exists for solid non-CNS-tumor patients. To get a better understanding of the potential neurotoxic mechanisms of non-CNS-directed chemotherapy during childhood, we performed a comprehensive literature review of this topic. Here, we provide an overview of preclinical and clinical studies investigating neurotoxicity associated with chemotherapy in the treatment of pediatric solid non-CNS tumors. Research to date suggests that chemotherapy has deleterious biological and psychological effects, with animal studies demonstrating histological evidence for neurotoxic effects of specific agents and human studies demonstrating acute neurotoxicity. Although the existing literature suggests potential neurotoxicity throughout neurodevelopment, research into the long-term neurocognitive sequelae in survivors of non-CNS cancers remains limited. Therefore, we stress the critical need for neurodevelopmental focused research in children who are treated for solid non-CNS tumors, since they are at risk for potential neurocognitive impairment.