Academic achievement after a CT examination toward the head in childhood: Follow up of a randomized controlled trial.

INTRODUCTION: Increasing use of CT examinations has led to concerns of possible negative cognitive effects for children. The objective of this study is to examine if the ionizing radiation dose from a CT head scan at the age of 6-16 years affects academic performance and high school eligibility at the end of compulsory school. MATERIALS AND METHODS: A total of 832 children, 535 boys and 297 girls, from a previous trial where CT head scan was randomized on patients presenting with mild traumatic brain injury, were followed. Age at inclusion was 6-16 years (mean of 12.1), age at follow up 15-18 years (mean of 16.0), and time between injury and follow up one week up to 10 years (mean of 3.9). Participants' radiation exposure status was linked with the total grade score, grades in mathematics and the Swedish language, eligibility for high school at the end of compulsory school, previously measured GOSE-score, and their mothers' education level. The Chi-Square Test, Student's t-Test and factorial logistics were used to analyze data. RESULTS: Although estimates of school grades and high school eligibility were generally higher for the unexposed, the results showed no statistically significant differences between the exposed and unexposed participants in any of the aforementioned variables. CONCLUSIONS: Any effect on high school eligibility and school grades from a CT head scan at the age of 6-16 years is too small to be detected in a study of more than 800 patients, half of whom were randomly assigned to CT head scan exposure.

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.

BACKGROUND: Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. METHODS: We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. RESULTS: PRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. CONCLUSIONS: Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

Cognitive function following head CT in childhood: a randomized controlled follow-up trial.

Background The question has been raised whether low dose radiation toward the brain in childhood can affect cognitive functions. Purpose To examine if a head computed tomography (CT) examination in childhood affect later cognitive functions. Material and Methods A total of 147 participants (67 girls/women, 80 boys/men) from a previous randomized controlled trial on management strategies after mild head injury (head CT examination or in-hospital observation) were followed up. Participants were aged 6-16 years (mean age = 11.2 ± 2.8) at first inclusion and 11-24 years (mean age = 17.8 ± 2.9) at follow-up. Computerized neuropsychological measures used for the assessment were motor speed and coordination, reaction time, selective attention, visuospatial ability, verbal and non-verbal short-term and long-term memory, and executive function tests from the neurocognitive test battery EuroCog and the Wechsler Memory Scale III. Results were analyzed with Student's t-tests and multivariate analyses adjusting for sex, age at time of injury/exposure, and age at assessment were performed with Factorial ANOVAs. Results The exposed and unexposed groups did not differ in any of the neuropsychological measures and results did not change when sex, age at time of injury/exposure, and age at assessment were included in the analyses. Conclusion A head CT examination at the age of 6-16 years does not seem to affect later cognitive functions.

Cognitive, psychosocial, somatic and treatment factors predicting return to work after breast cancer treatment.

BACKGROUND: Breast cancer (BC) may affect the ability to work. In this study, we want to identify any associations between cognitive, psychosocial, somatic and treatment factors with time to return to work (RTW) among women treated for BC. METHODS AND PARTICIPANTS: At eight (baseline) and 11(follow-up) months after BC diagnosis, women who had received adjuvant treatment for early BC at Stockholm South General Hospital completed the Headminder neuropsychological tests to obtain the Cognitive Stability Index (CSI), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module. At both time points, we compared the scores from women who had returned to work with those who had not. We also reviewed the medical certificates of women still on sick leave at 8, 11 and 18 months after diagnosis to determine why they had not returned to work. RESULTS: At baseline, 29 of 45 enroled women were working and 15 were not (one dropped out after baseline testing). The 14 women still not working 11 months after BC diagnosis had more advanced BC (OR = 3.64, 95% CI 2.01-7.31), lymph-node involvement (OR = 18.80, 95% CI 5.32-90.69) and Her 2-positive tumours (OR = 10.42,95% CI 2.19-65.32) than did working women. None of the scores for the four cognitive domains changed significantly at follow-up in either group. Comments on the medical certificates generally supported these findings. Independently of any adjuvant cancer therapy, overall quality of life improved and most women did RTW 18 months after BC diagnosis. CONCLUSIONS: Chemotherapy is associated with longer periods of sick leave. Cognitive functions do not predict RTW. Independently of any adjuvant therapy, most women eventually RTW in a few months. The ability to predict RTW after BC treatment should help prepare higher-risk patients for delayed RTW and allow earlier interventions to restore their social relations and quality of life.

Neurocognitive function in long-term treated schizophrenia: a five-year follow-up study.

Neurocognitive deficits are a core feature of schizophrenia. Deficits covering a wide range of functions have been well documented. However there is still a lack of longitudinal studies regarding the development of neurocognitive impairment. The current study examined the effect of time in long-term treated patients with schizophrenia and healthy controls on cognitive functions. A neurocognitive test-battery was administered to 36 patients and 46 controls on two occasions with approximately 4.5 years interval. Patients performed significantly worse on all measures on both occasions. The only significant decline over time was the ability to shift mental set between different rules or categories (measured by Trail Making Test B). This decline was present in both patients and controls. Improvement on attention (tested by Continuous Performance Test) was found in patients only and improvement on verbal learning (tested by Rey Auditory Verbal Learning Test) was found only in controls. Education was significantly related to outcome in patients and age was related to outcome in controls. We conclude that neurocognitive function is relatively stable over 4.5 years in patients with long-term treated schizophrenia, in line with previous scientific research. The authors discuss the impact of age and education and limitations of the study.

Effects of adjuvant treatment on cognitive function in women with early breast cancer.

PURPOSE: Whether adjuvant therapy impairs cognitive function in women with breast cancer (BC) is unclear. We determined the effects of adjuvant therapy on cognitive function in women with early BC. METHODS: We consecutively and prospectively enrolled women aged 40-69 years who had a positive radiographic finding from the mammography screening program at Stockholm South General Hospital. All women completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention before diagnosis (T1), after surgery and before adjuvant treatment (T2), 6 months after start of adjuvant treatment (T3), and after another 3 months of follow-up (T4). Women with BC were divided into those receiving chemotherapy, hormone therapy, or no adjuvant medical therapy. Women without a diagnosis of BC served as healthy controls. RESULTS: Of the 146 women enrolled, 77 had BC of whom 18 received chemotherapy; 45, hormone therapy, and 14, no adjuvant medical therapy; 69 were healthy controls. Memory scores for women with BC were significantly lower than those for controls over time, even after controlling for age and education. Memory and response speed scores were lower after chemotherapy than before (P<0.01 for both). Processing speed and attention improved significantly over time in all groups, a result consistent with a practice effect. CONCLUSION: Our results indicate subtle changes related to time course and treatment. Especially, that chemotherapy may impair memory and response speed in women with BC, consistent with those reported by BC survivors after adjuvant medical treatment.

The effects of breast cancer diagnosis and surgery on cognitive functions.

BACKGROUND: Women with breast cancer (BC) report cognitive impairment. Receiving a BC diagnosis may have a negative psychological impact. We sought to determine whether a diagnosis of BC and subsequent surgical treatment reduced cognitive function. MATERIAL AND METHODS: We recruited women, who had a positive radiographic finding, consecutively from the mammography screening program at Stockholm South General Hospital. All subjects completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention at enrolment (T1, Baseline). CSI was administered again, after BC was ruled out, or after sector resection or mastectomy, if BC was confirmed by cytology or biopsy (T2, Retest). RESULTS AND CONCLUSION: Of the 148 women approached, 146 were enrolled; 69 were healthy and 77 had BC. Comparison between groups at baseline, according to independent t-test, showed significant differences in response speed and processing speed. Cognitive abilities did not decline in either group on any of the measured domains. Our results suggest that a diagnosis of BC and subsequent surgery is not associated with substantial cognitive decline at retest. However, the lack of improvement in attention at retest among BC patients may be suggestive of a decline.

Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults.

Relationships between prefrontal and temporal lobe grey matter volumes as assessed by magnetic resonance imaging and neurocognitive test results have been reported in schizophrenia. This investigation aimed to localize brain regions where cortical thickness and neurocognitive performance were related, and investigate if such relationships might differ in schizophrenia patients and healthy controls. Sixty-seven patients with schizophrenia and 69 healthy controls were characterized by neurocognitive testing and by brain cortical thickness maps. Putative cortical thickness/cognitive score relationships were investigated with contrast analyses of general linear models for the combined sample. Regions in which relationships were present were further investigated for diagnostic interaction. In the combined sample, significant positive relationships were found between frontal, temporal and occipital regions and tests for verbal IQ, verbal learning and executive functions. Diagnostic interaction was found for the relationships between verbal IQ and the right temporo-occipital junction and the left middle occipital gyrus. In conclusion, the significant relationships between cortical thickness and neurocognitive performances were localized in brain areas known to be involved in cognition. The relationships were similar in patients and controls, except for the right temporo-occipital and left occipital cortical areas, indicating a disrupted structure-function relationship in patients with schizophrenia compared to healthy control subjects.

Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients.

CONTEXT: Capsulotomy is sometimes used as a treatment of last resort in severe and treatment-refractory cases of obsessive-compulsive disorder (OCD). OBJECTIVE: To evaluate the long-term efficacy and safety of capsulotomy in OCD. DESIGN: Noncontrolled, long-term follow-up trial (mean of 10.9 years after surgery). SETTING: University hospital referral center. PATIENTS: Twenty-five consecutive patients with OCD who underwent capsulotomy from 1988 to 2000. INTERVENTION: Unilateral or bilateral capsulotomy. Lesions were created by means of radiofrequency heating (thermocapsulotomy) or gamma radiation (radiosurgery, gammacapsulotomy). MAIN OUTCOME MEASURE: Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) score. RESULTS: The mean Y-BOCS score was 34 preoperatively and 18 at long-term follow-up (P < .001). Response (defined as > or = 35% reduction at long-term follow-up compared with baseline) was seen in 12 patients at long-term follow-up. Nine patients were in remission (Y-BOCS score, < 16) at long-term follow-up. Only 3 patients were in remission without adverse effects at long-term follow-up. Response rates did not differ significantly between surgical methods. A mean weight gain of 6 kg was reported in the first postoperative year. Ten patients were considered to have significant problems with executive functioning, apathy, or disinhibition. Six of these 10 patients had received high doses of radiation or had undergone multiple surgical procedures. Results of our magnetic resonance imaging analysis in 11 patients suggest that the OCD symptom reduction may be increased by reducing the lateral extension of the lesions, and a reduction in the medial and posterior extension may limit the risk of adverse effects (ie, smaller lesions may produce better results). CONCLUSIONS: Capsulotomy is effective in reducing OCD symptoms. There is a substantial risk of adverse effects, and the risk may vary between surgical methods. Our findings suggest that smaller lesions are safer and that high radiation doses and multiple procedures should be avoided.

Gender differences in the prediction of 5-year outcome in first episode psychosis.

OBJECTIVE: To examine gender differences in prediction of long-term outcome in first episode psychosis (FEP). METHOD: Eighty-one male and 72 female FEP patients were compared regarding the sensitivity and specificity of the Predictive Rating Scale (PRS). The contributions of pre-admission clinical and socio-demographic characteristics to a poor 5-year outcome were analysed for males and females separately. Gender differences in the relations between predictors and outcome were examined using the equality of correlation comparing correlation coefficients. RESULTS: The sensitivity of the PRS was significantly better for males than for females. The following items: 'the highest Global Assessment of Functioning (GAF) the year before first admission < or =70' and 'GAF at first admission < or =30' explained most of the variance of a poor 5-year outcome for males, whereas for females the corresponding items were 'the highest educational level is compulsory school', 'living with parents' and 'contact with friends < or =2-3 times/month'. When the PRS was adapted assigning a weight of two to the item 'the highest educational level is compulsory school' for females, the sensitivity increased. CONCLUSION: This study revealed that the predictors for poor outcome differ between male and female patients with FEP.

Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression.

BACKGROUND: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. METHODS: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. RESULTS: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. CONCLUSION: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.

Kinetics of tyrosine transport and cognitive functioning in schizophrenia.

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.

Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients.

OBJECTIVE: The objective of the present study was to evaluate the long-term efficacy and safety of capsulotomy in patients with anxiety disorders. METHOD: Twenty-six patients who had undergone bilateral thermocapsulotomy were followed up 1 year after the procedure and after a mean of 13 years. Primary diagnoses were generalized anxiety disorder (N=13), panic disorder (N=8), and social phobia (N=5). Measures of psychiatric status included symptom rating scales and neuropsychological testing. Ratings were done by psychiatrists not involved in patient selection or postoperative treatment. A quantitative magnetic resonance imaging (MRI) evaluation was conducted to search for common anatomic denominators. Seventeen of the 23 patients who were alive at long-term follow-up were followed up in person, and one was interviewed by telephone; the relatives of these 18 patients were interviewed. RESULTS: The reduction in anxiety ratings was significant both at 1-year and long-term follow-up. Seven patients, however, were rated as having substantial adverse symptoms; the most prominent adverse symptoms were apathy and dysexecutive behavior. Neuropsychological performance was significantly worse in the patients with adverse symptoms. No common anatomic denominator could be found in responders in the analysis of MRI scans. CONCLUSIONS: Thermocapsulotomy is an effective treatment for selected cases of nonobsessive anxiety but may carry a significant risk of adverse symptoms indicating impairment of frontal lobe functioning. These findings underscore the importance of face-to-face assessments of adverse symptoms.