Cognitive impairments and recovery in patients with work-related stress complaints - four years later.

Patients on sick leave due to work-related stress often present with cognitive complaints. The primary aim of this prospective cohort study was to examine potential long-term consequences of previous ongoing work-related stress in terms of cognitive functioning four years after initial professional care seeking. We tested a group of patients with work-related stress complaints with a comprehensive neuropsychological test battery. Patients were examined at a department of occupational medicine and tested at baseline, one-year follow-up and four-year follow-up. At each time point, we compared the performance of patients with healthy controls matched pairwise on sex, age and length of education. This paper presents the results from the four-year follow-up. Patients improved on their neuropsychological test performance during the four years but the main improvements took place during the first year. At baseline, the main impairments in the patient group concerned executive function and mental speed. At four-year follow-up, patients displayed slightly lower scores on the neuropsychological tests relative to controls but only the difference on immediate memory was significant corresponding to a small effect size (Cohen's d). More than half of the patients who participated in the four-year follow-up reported that they felt only slightly or partially recovered. The level of work participation among the former patients improved considerably during the four-year follow-up period.Lay SummaryThis study examines the long-term consequences of work-related stress in terms of cognitive functioning and recovery four years after initial professional care seeking. After four years, patients continued to display significantly lower memory scores than controls but no other significant differences between the groups were found on neuropsychological tests. Levels of work participation among patients improved considerably over time, yet, more than half of the former patients who participated in the four-year follow-up did not feel completely recovered.

Perceived stress, disturbed sleep, and cognitive impairments in patients with work-related stress complaints: a longitudinal study.

Patients on sick leave due to work-related stress often present with cognitive impairments as well as sleep disturbances. The aim of this longitudinal study was to examine the role of perceived stress and sleep disturbances in the longitudinal development in cognitive impairments in a group of patients with prolonged work-related stress (N = 60) during a period of 12 months following initial professional care-seeking. Objective cognitive impairments (neuropsychological tests) were measured on two occasions - at initial professional care-seeking and at 12-month follow-up. Questionnaires on perceived stress, sleep disturbances, and cognitive complaints were completed seven times during the 12 months which facilitated multilevel analysis with segregation of within-person (change) and between-person (baseline level) components of the time-varying predictors (perceived stress and sleep disturbances). Change in perceived stress was associated with concurrent and subsequent change in self-reported cognitive complaints over the period of 12 months and to a lesser extent the change in performance on neuropsychological tests of processing speed from baseline to 12-month follow-up. Change in sleep disturbances was also associated with concurrent and subsequent change in self-reported cognitive complaints over the 12 months but not with change on neuropsychological test performance. Although the mechanism behind the improvement in cognitive impairments in patients with work-related stress should be further explored in future studies, the results could suggest that improvement in cognitive impairments is partly mediated by decreasing levels of perceived stress and, to a lesser extent, decreasing levels of sleep disturbances. Lay summary This study examines the role of perceived stress and sleep disturbances in respect to the development of cognitive impairments (e.g. memory and concentration) in a group of patients with work-related stress. We found that change in cognitive impairments seems to be partly explained by change in perceived stress and, to a lesser extent, sleep disturbances over time. This could suggest that cognitive impairments can be reduced by stress management interventions which aim to reduce perceived stress and sleep disturbances but future studies are needed to confirm this interpretation.

Cognitive impairments in former patients with work-related stress complaints - one year later.

Patients on sick leave due to work-related stress often present with cognitive impairments. The aim of this prospective cohort study was to examine the long-term consequences of prolonged work-related stress in terms of cognitive functioning one year after initial professional care seeking. We tested a group of patients with work-related stress with a comprehensive neuropsychological test battery at two occasions, one year apart. At both time points, we compared the performance of patients with healthy controls matched pairwise on sex, age and length of education. This paper presents the results from the one-year follow-up. When adjusting for practice effects, patients improved on measures of prospective memory and processing speed. However, patients continued to perform worse than controls on all tests, though only half of the comparisons reached statistical significance. The effect sizes of the differences between the two groups at one-year follow-up were small to medium. In conclusion, former patients with prolonged work-related stress improved, but they continued to perform worse than controls after one year. In the acute phase, the largest impairments were related to executive function and mental speed but at follow-up memory impairments also became apparent.

Can memory and executive functions in patients with obsessive-compulsive disorder predict outcome of cognitive behavioural therapy?

BACKGROUND: Most studies find that patients with obsessive-compulsive disorder (OCD) have impaired memory and executive functions. Cognitive behavioural therapy (CBT) is the recommended psychotherapeutic treatment of patients with OCD. We hypothesized that impairments in memory and executive functions would predict poor outcome of CBT. AIM: To investigate whether memory and executive functions in patients with OCD could predict outcome of CBT. METHODS: We assessed 39 patients with OCD before CBT with neuropsychological tests of memory and executive functions, the Hamilton Depression Rating Scale, and the Global Assessment of Functioning Scale. Furthermore, we assessed severity of OCD symptoms before and after CBT using the Yale-Brown Obsessive Compulsive Scale. RESULTS: There were no statistically significant differences between recovered (41%) and non-recovered patients (59%) on any neuropsychological test variables or on any baseline demographic variables. Furthermore, change in OCD symptoms was not predicted by neuropsychological test performances or baseline severity of OCD symptoms. The only statistically significant finding was that non-recovered patients had lower social functioning before CBT than recovered patients (p = 0.018, d = 0.797). CONCLUSIONS: Memory and executive functions in patients with OCD could not predict outcome of CBT, but level of social functioning may be a predictor of CBT outcome. Some of the main clinical implications are that we cannot use memory and executive functions, or baseline severity of OCD symptoms to determine which patients should be offered CBT.

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

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 (Cohen's 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.

Cognitive impairment in testicular cancer survivors 2 to 7 years after treatment.

PURPOSE: The aim of the present study was to determine the prevalence of cognitive impairment (CI) in a group of testicular (TC) survivors by comparing their neuropsychological test scores with normative data and to assess their performance in specific cognitive domains. METHODS: Seventy-two TC survivors were evaluated 2 to 7 years post-treatment with a neuropsychological test battery that assessed multiple cognitive domains-attention and working memory, processing speed, verbal fluency, learning and memory, and executive functioning. Test scores were compared with normative data, and CI status was calculated for each participant. RESULTS: In group-level analyses, survivors exhibited significantly impaired scores on a majority (9/12) of the neuropsychological outcomes (p < 0.01). In individual-level analyses, 62.5 % of the survivors were classified as having CI, significantly exceeding the expected normative frequency of 25 % (binomial test: p < 0.001). In particular, CI was observed in multiple outcomes related to verbal learning and memory (29 to 33 % of participants), visual learning and memory (14-28 %), processing speed (8-24 %), executive functioning (17 %), and attention and working memory (4-15 %). No association was found between treatment modality (surgery ± chemotherapy) and CI. CONCLUSIONS: The prevalence of CI in TC survivors was unexpectedly high, with survivors performing significantly worse than expected on a majority of the neuropsychological outcomes. While the findings are preliminary in nature, they still have important implications for the diagnosis and treatment of CI in TC survivors.

Are there reliable changes in memory and executive functions after cognitive behavioural therapy in patients with obsessive-compulsive disorder?

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) have impaired memory and executive functions, but it is unclear whether these functions improve after cognitive behavioural therapy (CBT) of OCD symptoms. The primary aim of this study was to investigate whether memory and executive functions change after CBT in patients with OCD. METHODS: We assessed 39 patients with OCD before and after CBT with neuropsychological tests of memory and executive functions. To correct for practice effects, 39 healthy controls (HCs) were assessed at two parallel time intervals with the neuropsychological tests. RESULTS: There were no changes in memory and executive functions after CBT in patients with OCD when results were corrected for practice effects. Patients performed worse on a test of visuospatial memory and organisational skills (Rey complex figure test [RCFT]) compared to HCs both before and after CBT (ps = .002-.036). CONCLUSIONS: The finding of persistent poor RCFT performances indicates that patients with OCD have impaired visuospatial memory and organisational skills that may be trait-related rather than state-dependent. These impairments may need to be considered in treatment. Our findings underline the importance of correcting for practice effects when investigating changes in cognitive functions.

Neuropsychological test performance in social anxiety disorder.

BACKGROUND: The effect of state factors on neuropsychological performance in social anxiety disorder (SAD) has not been thoroughly investigated and the overall neuropsychological profile remains poorly understood. AIMS: The primary objective of the study was to investigate the effect of state anxiety and state emotion suppression on neuropsychological performance in SAD. METHODS: A neuropsychological test battery was administered before and after an anxiety manipulation (instruction to give a video-recorded speech) to 42 patients with SAD and to a gender and education matched group of 42 healthy controls (HCs). RESULTS: Overall, participants with SAD performed worse than HCs on processing speed, visuospatial construction, visuospatial memory, verbal learning and word fluency, of which only the decreased visuospatial construction performance was considered clinically significant. State anxiety was not associated with neuropsychological performance at baseline, whereas state emotion suppression predicted decreased visuospatial memory in HCs and decreased verbal learning in the SAD group. Both groups performed better on working memory, processing speed and spatial anticipation, and worse on verbal learning and memory following the anxiety manipulation. The increase in state anxiety was associated with the decrease in verbal learning in both groups. CONCLUSIONS: Participants with SAD showed clinically significant difficulties with visuospatial construction and may experience verbal learning difficulties when suppressing emotions and experiencing an increase in anxiety.

Memory and executive functions in patients with obsessive-compulsive disorder.

OBJECTIVE: We investigated whether patients with obsessive-compulsive disorder have poorer memory and executive functions than healthy controls. BACKGROUND: The relatively inconsistent previous findings on this question reflect a lack of well-matched control groups, the inclusion of patients with comorbidity, and the use of noncomparable neuropsychological tests to assess memory and executive functions. METHODS: We used well-accepted neuropsychological tests of memory and executive functions to assess 42 patients who had obsessive-compulsive disorder without comorbidity, and 42 healthy controls. We matched the patients and controls pairwise by sex, age, and years of education. RESULTS: The patients performed significantly worse than the controls on the Rey Complex Figure Test, which assesses visuospatial memory and organizational skills. This group difference remained after we controlled for age, education, intelligence, and severity of depressive symptoms. CONCLUSIONS: The findings indicate that patients with obsessive-compulsive disorder may have impaired visuospatial memory and organizational skills, and these impairments should be considered in treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT00792038.

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.

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.

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. METHODS: In the present study we examine whether cancer patients (n=34) receiving chemotherapy differed in cognitive changes during treatment compared with cardiac patients (n=12) and healthy controls (n=12) tested at 3-4 months interval. RESULTS: Our results showed no differences with respect to changes in cognitive performance over time between cancer patients in chemotherapy, cardiac patients, and healthy controls. In addition, the number of individuals showing reliable decline or improvement on cognitive tests did not differ between groups. CONCLUSION: Taken together, our results do not support a hypothesis of cognitive side-effects of standard-dose chemotherapy in breast cancer patients.

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.

Anxiety and depression in Klinefelter syndrome: The impact of personality and social engagement.

Klinefelter syndrome (KS) (47, XXY) is the most common sex chromosome disorder, with a prevalence of 1 in every 660 newborn males. Despite the profound adverse effects of anxiety and depression, and their greater prevalence in KS populations, no research has been conducted to date to identify the determinants of anxiety and depression among patients with KS. We examined the relationships between personality traits, social engagement, and anxiety and depression symptoms among KS patients (n = 69) and a group of male controls (n = 69) matched for age and years of education. KS patients experienced more anxiety and depression symptoms than control participants. Neuroticism was the strongest and most consistent mediator between KS and both anxiety and depression symptoms. This research suggests that neuroticism may play a central role in attention switching, anxiety and depression among patients with Klinefelter syndrome. The central role of neuroticism suggests that it may be used to help identify and treat KS patients at particularly high-risk for attention-switching deficits, anxiety and depression.

The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome.

INTRODUCTION: The determinants of cognitive deficits among individuals with Klinefelter syndrome (KS) are not well understood. This study was conducted to assess the impact of general intelligence, personality, and social engagement on cognitive performance among patients with KS and a group of controls matched for age and years of education. METHODS: Sixty-nine patients with KS and 69 controls were assessed in terms of IQ, NEO personality inventory, the Autism Spectrum Quotient (AQ) scale, and measures of cognitive performance reflecting working memory and executive function. RESULTS: Patients with KS performed more poorly on memory and executive-function tasks. Patients with KS also exhibited greater neuroticism and less extraversion, openness, and conscientiousness than controls. Memory deficits among patients with KS were associated with lower intelligence, while diminished executive functioning was mediated by both lower intelligence and less social engagement. CONCLUSION: Our results suggest that among patients with KS, memory deficits are principally a function of lower general intelligence, while executive-function deficits are associated with both lower intelligence and poorer social skills. This suggests a potential influence of social engagement on executive cognitive functioning (and/or vice-versa) among individuals with KS, and perhaps those with other genetic disorders. Future longitudinal research would be important to further clarify this and other issues discussed in this research.

Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation.

Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49) responded to whether the words "GREEN" or "RED" were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying "GREEN" or "RED" had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.

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: Cohen's 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.

Cognitive status does not predict motor gain from post stroke constraint-induced movement therapy.

BACKGROUND: Constraint-Induced Movement Therapy (CIMT) is an evidence-based rehabilitation intervention for stroke. Several factors influence the motor gain from CIMT, including age and level of impairment. However, it is currently unknown to what extent cognitive status affects motor gain during CIMT. OBJECTIVE: The aim of this study was to investigate whether cognitive and emotional status affects motor improvement during two weeks of CIMT and retention of the gain at three months follow-up. METHODS: Twenty stroke patients (3-12 months post stroke) completed two weeks of CIMT. Motor performance was measured using the Wolf Motor Function Test (WMFT). Cognitive and emotional status was measured with a comprehensive neuropsychological test battery and a questionnaire on emotional status. All measures were performed at baseline, after two weeks of training, and at three months follow-up. RESULTS: We found no significant correlation between cognitive or emotional measures at baseline and improvement in motor performance post training. Also, cognitive and emotional status did not correlate with motor retention at three months follow-up. CONCLUSIONS: We found no evidence to support that cognitive performance in stroke patients can predict motor gain from CIMT.

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.