Susan M. Byrne

Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia

Background: The prognostic implications of cognitive impairment in amyotrophic lateral sclerosis (ALS) are not established. Objectives: To investigate the survival effect of the comorbid frontotemporal dementia (FTD) and to determine whether, in the absence of dementia, impairment in different cognitive domains affects outcome. Methods: A prospective population-based study of incident cases of ALS in the Republic of Ireland included home-based neuropsychological assessments using age-, sex-, and education-matched controls. Four cognitive domains were evaluated: executive function, memory, language, and visuospatial skills. Results: Mean age of the participants (n = 139) was 63.3 years; 61.2% were male and 35.3% had bulbar-onset ALS. Factors associated with shorter survival included age more than 60, severe disability at baseline, shorter delay to diagnosis, and early respiratory involvement. Comorbid FTD was associated with significantly shorter survival time (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.04–6.85, p = 0.041). In patients with ALS without dementia, the presence of executive dysfunction was significantly associated with shorter survival. This was confirmed in a multivariate model that included age, delay to diagnosis, disease severity at baseline, education, and respiratory status (HR 3.44, 95% CI 1.45–8.18, p = 0.005). In the absence of executive dysfunction, single or multi-domain impairment in other cognitive domains had no significant effect on survival. Conclusion: Comorbid frontotemporal dementia is a negative prognostic indicator. In patients with ALS without dementia, executive dysfunction, but not impairment in other cognitive domains, is an important negative prognostic indicator.

Elite athletes: effects of the pressure to be thin.

This study represented the first attempt to examine the prevalence of eating disorders in a large sample of both male and female elite athletes compared to a matched control group of non-athletes. The subjects were 263 Australian elite athletes representing a variety of sports, and 263 non-athletes. All subjects were interviewed using the Composite International Diagnostic Interview and completed a number of self-report questionnaires. Both male and female athletes competing in sports that emphasise a lean body shape or a low body weight evidenced a significantly higher prevalence of eating disorders and eating disorder symptoms than other athletes and non-athletes. The results suggest that athletes do, in fact, have a higher prevalence of eating disorders than non-athletes. However, it is not so much being an athlete that places an individual at increased risk for developing an eating disorder; rather it is athletes competing in sports which emphasise the importance of a thin body shape or a low body weight who appear to be particularly vulnerable.

Eating disorders in athletes: A review of the literature

Over the last two decades an increasing amount of research has begun to examine the issue of eating disorders in athletes. While a number of studies in this area have been published, the results have not been able to clarify the nature of the relationship between athletic involvement and eating problems. This review critically evaluates existing studies of eating disorders in athletes, highlighting various methodological limitations. Studies are grouped under three main headings: uncontrolled studies; controlled studies; and studies comparing athletes with different body type requirements. A fourth section of the paper evaluates studies which have addressed the issue of gender differences in eating disorders among athletes. Suggestions are made for guidelines that will improve future research in this area.

The effectiveness of enhanced cognitive behavioural therapy for eating disorders: An open trial

The aim of this study was to examine the effectiveness of Enhanced Cognitive Behaviour Therapy (CBT-E) for eating disorders in an open trial for adults with the full range of eating disorders found in the community. The only previously published trial of CBT-E for eating disorders was a randomised controlled trial (RCT) conducted in the U.K. for patients with a BMI ≥ 17.5. The current study represents the first published trial of CBT-E to include patients with a BMI<17.5. The study involved 125 patients referred to a public outpatient clinic in Perth, Western Australia. Patients attended, on average, 20-40 individual sessions with a clinical psychologist. Of those who entered the trial, 53% completed treatment. Longer waiting time for treatment was significantly associated with drop out. By the end of treatment full remission (cessation of all key eating disorder behaviours, BMI ≥ 18.5 kg/m(2), not meeting DSM-IV criteria for an eating disorder) or partial remission (meeting at least 2 these criteria) was achieved by two thirds of the patients who completed treatment and 40% of the total sample. The results compared favourably to those reported in the previous RCT of CBT-E, with one exception being the higher drop-out rate in the current study. Overall, the findings indicated that CBT-E results in significant improvements, in both eating and more general psychopathology, in patients with all eating disorders attending an outpatient clinic.

Cognitive changes predict functional decline in ALS A population-based longitudinal study

Objective: To determine whether cognitive status in patients with amyotrophic lateral sclerosis (ALS) is a useful predictor of attrition and motor and cognitive decline. Methods: Cognitive testing was undertaken in a large population-based cohort of incident ALS patients using a longitudinal, case-control study design. Normative data for neuropsychological tests were generated using age-, sex-, and education-matched healthy controls who also underwent repeated assessments. Data were analyzed to generate models for progression/spread. Results: One hundred eighty-six patients with ALS who had no evidence of C9orf72 hexanucleotide repeat expansion were enrolled. A second and third assessment were undertaken in 98 and 46 of the patients with ALS, respectively. Executive impairment at the initial visit was associated with significantly higher rates of attrition due to disability or death and faster rates of motor functional decline, particularly decline in bulbar function. Decline in cognitive function was faster in patients who were cognitively impaired at baseline. Normal cognition at baseline was associated with tendency to remain cognitively intact, and with slower motor and cognitive progression. Conclusions: Non-C9orf72–associated ALS is characterized by nonoverlapping cognitive subgroups with different disease trajectories. These findings have important implications for models of ALS pathogenesis, and for future clinical trial design.

Multiparametric MRI study of ALS stratified for the C9orf72 genotype

Objective: To describe the patterns of cortical and subcortical changes in amyotrophic lateral sclerosis (ALS) stratified for the C9orf72 genotype. Methods: A prospective, single-center, single-protocol, gray and white matter magnetic resonance case-control imaging study was undertaken with 30 C9orf72-negative patients with ALS, 9 patients with ALS carrying the C9orf72 hexanucleotide repeat expansion, and 44 healthy controls. Tract-based spatial statistics of multiple white matter diffusion parameters, cortical thickness measurements, and voxel-based morphometry analyses were carried out. All patients underwent comprehensive genetic and neuropsychological profiling. Results: A congruent pattern of cortical and subcortical involvement was identified in those with the C9orf72 genotype, affecting fusiform, thalamic, supramarginal, and orbitofrontal regions and the Broca area. White matter abnormalities in the C9orf72-negative group were relatively confined to corticospinal and cerebellar pathways with limited extramotor expansion. The body of the corpus callosum and superior motor tracts were affected in both ALS genotypes. Conclusions: Extensive cortical and subcortical frontotemporal involvement was identified in association with the C9orf72 genotype, compared to the relatively limited extramotor pathology in patients with C9orf72-negative ALS. The distinctive, genotype-specific pathoanatomical patterns are consistent with the neuropsychological profile of the 2 ALS cohorts. Our findings suggest that previously described extramotor changes in ALS could be largely driven by those with the C9orf72 genotype.

Basal ganglia involvement in amyotrophic lateral sclerosis

Objectives: To characterize the nature and extent of basal ganglia involvement in amyotrophic lateral sclerosis (ALS) genotypes in vivo. Methods: Forty-four healthy controls and 39 patients with ALS were included in the study. Thirty patients with ALS had a negative C9orf72 status and 9 patients with ALS carried the C9orf72 hexanucleotide repeat expansion. High-resolution T1-weighted MRI data were used for model-based subcortical registration and segmentation. Fifteen subcortical structures were studied with both volumetric and vertex-wise approaches. Changes in basal ganglia diffusivity parameters were also assessed. Results: Using age as a covariate, patients with ALS who were C9orf72 repeat negative showed significant volume reductions in the left caudate nucleus (p = 0.01), left hippocampus (p = 0.007), and right accumbens nucleus (p = 0.001) compared with healthy controls. Vertex-wise shape analyses revealed changes affecting the superior and inferior aspects of the bilateral thalami, the lateral and inferior portion of the left hippocampus, and the medial and superior aspect of the left caudate. Basal ganglia pathology was more extensive in patients with ALS carrying the C9orf72 hexanucleotide repeat expansion. Conclusions: ALS is associated with widespread basal ganglia involvement. Caudate nucleus, hippocampus, and nucleus accumbens atrophy are key features of ALS. Dysfunction of frontostriatal networks is likely to contribute to the unique neuropsychological profile of ALS, dominated by executive dysfunction, apathy, and deficits in social cognition. Our quantitative imaging findings are consistent with postmortem studies and indicate that subcortical gray matter structures should be included in future biomarker studies of ALS.

Why do some overweight children experience psychological problems? The role of weight and shape concern

OBJECTIVE To examine the associations between weight status, weight and shape concern, self-esteem, body dissatisfaction and depression in children. METHODS Interviews were conducted with 7- to 13-year-old overweight (n = 89) and healthy weight (n = 118) children, using the Child Eating Disorder Examination, Self-Perception Profile for Children, Childrens Body Image Scale and Child Depression Inventory. RESULTS Overweight children were more concerned about weight and shape than healthy weight children. After controlling for BMI z-score, children with high weight and shape concern reported lower self-esteem, higher body dissatisfaction and higher depression than children with low weight and shape concern. Concern about weight and shape mediated the relationships between BMI z-score and low self-esteem, body dissatisfaction and depression. CONCLUSIONS Results support the hypothesis that differences in weight and shape concern, within samples of overweight and healthy weight children, can account for differences in degree of psychological distress. Findings have implications for the prevention and treatment of psychological problems in overweight children.

Body dissatisfaction and the effects of perceptual exposure on body norms and ideals.

OBJECTIVE Body dissatisfaction is of high prevalence among women all over the Western world. It is often suggested that sociocultural processes are the main cause of such widespread dissatisfaction. Here, we consider how perceptual effects may influence ideas of body normality and body ideals. METHOD Women who varied on a measure of body dissatisfaction rated a range of bodies for how normal and ideal they looked. They were exposed to either thin or fat bodies, and then they rerated the bodies. RESULTS Womens perceptions of body normality and ideal were easily malleable by exposure. In addition, greater body dissatisfaction and internalization of the thin Western ideal were related to (i) a smaller most normal and ideal body, (ii) a greater discrepancy between the most normal and most ideal-rated body, and (iii) a reduced effect of exposure to fat bodies. DISCUSSION Reduced updating of perceptions of body normality and body ideals in response to experience may be one mechanism that maintains body dissatisfaction.

The eating disorder examination: Norms and construct validity with young and middle adolescent girls

OBJECTIVE The purpose of this investigation was to examine the norms and construct validity of the eating disorder examination (EDE) with young and middle adolescent girls. METHOD The EDE was completed with 699 female twins aged 12-15 years. Four aspects of construct validation were examined: a factor analysis, internal reliability of the subscales, differences across the different age groups, and correlations between the variables. Results were reported separately for Twin 1 and 2 in order to examine the stability of the findings. RESULTS The factor structure of the EDE was unstable, except for an eight-item derived weight and shape concern subscale. This scale, along with the total score and the shape concern subscale had good internal reliability. The cognitive diagnostic items performed strongly in terms of discriminating between age groups and presence of disordered eating. CONCLUSION Given the central role of weight and shape concern and the importance of weight and shape in diagnosis and predicting onset of disordered eating, it would appear that the EDE is likely to perform well as both a diagnostic and predictive tool. Caution should be exercised with respect to the use and interpretation of the individual subscales in nonclinical populations of young adolescent girls.