Anders Degn Pedersen

No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy

Objective: A number of cross‐sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls, suggesting that chemotherapy could be associated with cognitive side‐effects. Recently published prospective studies question this hypothesis, but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy.

Long-term cognitive function following chemotherapy in patients with testicular cancer.

Cancer patients frequently report cognitive complaints following chemotherapy, but the results from the available studies, mainly of women with breast cancer, are inconsistent. Our aim was to compare cognitive function of men with testicular cancer (TC) who had orchiectomy and chemotherapy (bleomycin, etoposide, cisplatin) with men who had orchiectomy only or orchiectomy and radiotherapy. Thirty-six chemotherapy patients and 36 nonchemotherapy patients were tested 2-7 years after treatment for TC with standardized neuropsychological tests. Chemotherapy and nonchemotherapy patients displayed similar performances on cognitive tests (p values adjusted for multiple comparisons: .63-1.00). Moreover, there was no difference in the proportion of cognitively impaired patients in the chemotherapy group (5.6%) compared to the nonchemotherapy group (8.3%) (chi2 = 0.22, p = .64). Our results are discordant with previous findings indicating cognitive impairment following chemotherapy and suggest that TC patients do not need to fear long-term cognitive consequences following chemotherapy.

A systematic review of neuropsychological performance in social anxiety disorder.

Background: Over the past few years, there has been an increasing interest in the neuropsychological performance of patients with anxiety disorders, yet the literature does not provide a systematic review of the results concerning adult patients with social anxiety disorder (SAD). Aims: The primary aim of this paper is to review the literature on neuropsychological performance in adult patients with SAD. Methods: This paper is a systematic review of empirical studies investigating neuropsychological performance as assessed by cognitive tests. Results: 30 papers were located comprising a total number of 698 adult patients with SAD. The review revealed indication for decreased performance regarding visual scanning and visuoconstructional ability as well as some indication for verbal memory difficulties. Conclusion: The impact of possible confounding variables on the neuropsychological performance is discussed. It is suggested that the decreased performance should be attributed to an increased level of situational anxiety, and an engagement in disorder-related, cognitively costly activities rather than trait-like cognitive dysfunctions. Future experimental studies are needed to explore the causal relationship between these constructs. Knowledge from such studies is important in order to improve the understanding of why SAD is such a disabling disorder, both educationally and interpersonally, and could assist in the planning and evaluation of psychotherapeutic treatment.

Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile

Brain imaging in Klinefelter syndrome (47, XXY) (KS), a genetic disorder characterized by the presence of an extra X chromosome, may contribute to understanding the relationship between gene expression, brain structure, and subsequent cognitive disabilities and psychiatric disorders. We conducted the largest to date voxel-based morphometry study of 65 KS subjects and 65 controls matched for age and education and correlated these data to neuropsychological test scores. The KS patients had significantly smaller total brain volume (TBV), total gray matter volume (GMV) and total white matter volume (WMV) compared to controls, whereas no volumetric difference in cerebral spinal fluid (CSF) was found. There were no differences in TBV, GMV, WMV or CSF between testosterone treated KS (T-KS) and untreated KS (U-KS) patients. Compared to controls, KS patients had significantly decreased GMV bilaterally in insula, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate classification analysis discriminated KS patients from controls with 96.9% (p < 0.001) accuracy. Regression analyses, however, revealed no significant association between GMV differences and cognitive and psychological factors within the KS patients and controls or the groups combined. These results show that although gene dosage effect of having and extra X-chromosome may lead to large scale alterations of brain morphometry and extended cognitive disabilities no simple correspondence links these measures.

Neuropsychology and brain morphology in Klinefelter syndrome – the impact of genetics

Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X‐chromosome inactivation and parent‐of‐origin of the extra X‐chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X‐chromosome inactivation pattern, CAG repeat length and parent‐of‐origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls. Grey matter (GM) volume of left insula was significantly decreased in KS patients with skewed X‐inactivation (z = 5.78) and we observed a borderline significant difference in global brain matter volume where KS patients with skewed X‐chromosome inactivation tended to have smaller brains. Skewed X‐inactivation, CAG repeat length and parent‐of‐origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression and anxiety or cognitive function. Interestingly our results regarding brain volumes indicate that X‐inactivation has an influence on GM volume in left insula and might also be related to global GM volume, indicating a possible effect of X‐linked genes on the development of GM volume in KS patient. Skewed X‐inactivation, CAG repeat length and parent‐of‐origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310)).

Web-based cognitive training for breast cancer survivors with cognitive complaints—a randomized controlled trial

Cognitive complaints are common amongst breast cancer survivors, and no standard treatment exists. The present study evaluates whether web‐based cognitive training can alleviate subjectively reported and objectively assessed cognitive complaints in a sample of breast cancer survivors. The primary and secondary outcomes were an objective measure of working memory and a measure of perceived cognitive functioning. Additional outcomes were neuropsychological tests of memory, executive function, working memory and questionnaire‐based assessment of anxiety, depression and somatization.

Anthropometry in Klinefelter syndrome - multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism

CONTEXT Klinefelter syndrome, 47, XXY (KS), is underdiagnosed partly due to few clinical signs complicating identification of affected individuals. Certain phenotypic traits are common in KS. However, not all aspects of the KS phenotype are well described. OBJECTIVE To describe anthropometry and body composition in KS and relate findings to biochemistry and X-chromosome related genetic markers. DESIGN, SETTING AND PARTICIPANTS Seventy three KS males referred to our clinic and 73 age-matched controls underwent comprehensive measurements of anthropometry and body composition in a cross-sectional, case-controlled study. Furthermore, genetic analysis for parental origin of the supernumerary X-chromosome, skewed X-chromosome inactivation and androgen receptor (AR) CAG repeat length was done. MAIN OUTCOME MEASURE Anthropometry and body composition in KS and the effect of genotype hereon. RESULTS KS males were taller (absolute difference: 5.1 cm, P < .001) with longer legs (5.7 cm, P < .001) compared with controls. Furthermore, 2D:4D was increased in KS males (relative effect size: Cohens d = 0.40), reflecting reduced fetal testosterone exposure. Also, bi-iliac width (0.41), waist (0.52), and hip circumference (0.47) (P < .02 for all), as well as total fat mass (0.74), abdominal fat mass (0.67), and total body fat percentage (0.84) was increased in KS males (P < .001 for all), while bitesticular volume was reduced (4.6). AR CAG repeat length was comparable in KS and controls, and among KS CAG correlated to arm length (P = .04), arm span (P = .01), and leg length (P = .04). Effects of parental origin of the supernumerary X-chromosome and skewed X-chromosome inactivation were negligible. CONCLUSIONS Anthropometry and body composition in KS is specific and dysmorphic and affected by AR CAG repeat length and decreased exposure to testosterone already during fetal life.

Work-related stress is associated with impaired neuropsychological test performance: a clinical cross-sectional study

Abstract Patients on sick leave due to work-related stress often complain about impaired concentration and memory. However, it is undetermined how widespread these impairments are, and which cognitive domains are most long-term stress sensitive. Previous studies show inconsistent results and are difficult to synthesize. The primary aim of this study was to examine whether patients with work-related stress complaints have cognitive impairments compared to a matched control group without stress. Our secondary aim was to examine whether the level of self-reported perceived stress is associated with neuropsychological test performance. We used a broad neuropsychological test battery to assess 59 outpatients with work-related stress complaints (without major depression) and 59 healthy controls. We matched the patients and controls pairwise by sex, age and educational level. Compared to controls, patients generally showed mildly reduced performance across all the measured domains of the neuropsychological test battery. However, only three comparisons reached statistical significance (p < 0.05). Effect sizes (Cohens d) were generally small to medium. The most pronounced differences between patients and controls were seen on tests of prospective memory, speed and complex working memory. There were no statistical significant associations between self-reported perceived stress level and neuropsychological test performance. In conclusion, we recommend that cognitive functions should be considered when evaluating patients with work-related stress complaints, especially when given advice regarding return to work. Since this study had a cross-sectional design, it is still uncertain whether the impairments are permanent. Further study is required to establish causal links between work-related stress and cognitive deficits.

Do cognitive functions in obsessive–compulsive disorder change after treatment? A systematic review and a double case report

Background: Neuropsychological and neuroimaging studies have documented that patients with obsessive–compulsive disorder (OCD) have cognitive difficulties dependent upon fronto-striatal circuits in the brain. It is, however, unclear whether the cognitive difficulties change after treatment. Answering this question could help establish whether cognitive difficulties in OCD are state dependent or more trait-like. Aim: To determine whether cognitive functions in OCD change after treatment, based on a systematic literature review, supplemented by a double case report of monozygotic twins with OCD. Methods: For the literature review, systematic searches were conducted in PubMed, Embase and PsycINFO from the earliest dates available to September 2010. For the double case report, monozygotic twins underwent blood samples and magnetic resonance imaging before treatment with cognitive behavioral therapy (CBT), antidepressants and small doses of antipsychotic medication. Before and after CBT they were assessed with measures of content and severity of OCD symptoms, and with a comprehensive battery of neuropsychological tests to assess cognitive functions. Results: Results from the studies under review (n = 14) were so inconsistent that it could not be concluded whether cognitive functions in OCD change after treatment. The twins improved some of their cognitive functions after treatment. Conclusions: A better understanding of whether cognitive dysfunctions in OCD are state dependent or trait-like could bring important implications in understanding the pathology and future treatment of OCD.

The relationship between cognitive functions, somatization and behavioural coping in patients with multiple functional somatic symptoms

Background and aims: Patients with multiple functional somatic symptoms (MFS) often express cognitive complaints. The aim of this descriptive study was to investigate whether these patients have cognitive deficits and whether the patients’ cognitive functioning relates to their experience of physical and psychological distress and to their use of pain-related coping strategies. Methods: Neuropsychological assessment of verbal ability, psychomotor speed, attention, working memory, perceptual organization and memory, was conducted on 22 MFS patients and 27 healthy age- and gender-matched controls. Psychological distress, health anxiety, health status and pain coping were measured with questionnaires [Symptom Checklist 90-Revised (SCL-somatization, SCL-depression, SCL-anxiety), the Whiteley-7 scale, the Short Form (SF-36) and the Coping Strategies Questionnaire (CSQ)]. Results: For patients, a high score on the SCL-somatization subscale was associated with poor performance on tests of attention and psychomotor speed, and with a high score on the coping scale Increasing behavioural activities. A high score on this coping scale was associated with poor performance on tests of verbal ability and executive functioning. After controlling for years of education, controls performed significantly better than patients on verbal as well as performance IQ scales but not on tests of memory. Conclusion: In the present study, we found that physical complaints are related to deficits in attention and psychomotor speed. Moreover, our results suggest that poor verbal skills may play a role in the development of MFS because of an increased tendency to apply behavioural/avoidant coping strategies. We suggest that treatment of MFS should involve training of attention as well as practicing the use of cognitive coping strategies.