Goal management training for improving fatigue in children and adolescents with acquired brain injuries: A 2-year follow-up of a randomised controlled trial.

To explore the long-term effectiveness of a paediatric adaptation of Goal Management Training (pGMT), relative to a psychoeducative program (pBHW), in reducing fatigue after pABI 2 years post-intervention. Thirty-eight youths and their parents completed the Paediatric Quality of Life - Multidimensional Fatigue Scale. Primary outcome measures were Total Fatigue Score, General fatigue, Cognitive fatigue, and Sleep/rest fatigue (parent-report). No significant differences in fatigue symptoms by the parental report was observed between the intervention groups at the 2-year follow-up (total score: F = .16, p = .69; general fatigue: F = .36, p = .55; sleep/rest: F = .48, p = .49; and cognitive fatigue: F = .09, p = .76), nor any time*group interactions (total score: F = .25, p = .86; general fatigue: F = .39, p = .76; sleep/rest: F = .20, p = .89; and cognitive fatigue: F = .08, p = .97). In total, 45% of the participants in the pGMT group and 25% in the pBHW group demonstrated a reliable positive clinical change. The significant improvements in fatigue symptoms that were demonstrated 6 months post-intervention could not be confirmed in this 2-year follow-up study. However, a continued positive tendency on most dimensions of fatigue for the participants in the pGMT group could be observed, suggesting that cognitive rehabilitation may help reduce fatigue.

Baseline long-term potentiation-like cortical plasticity is associated with longitudinal cortical thinning in healthy adults and in adults with bipolar disorder type II.

The precise neurobiological processes underlying cerebral cortical thinning in aging and psychiatric illnesses remain undetermined, yet aging- and synaptic dysfunction-related loss of synapses are potentially important mechanisms. We used long-term potentiation-like plasticity of the visual evoked potential as an index of synaptic function in the cortex and hypothesized that plasticity at baseline would be negatively associated with future cortical thinning in healthy adults and in adults with bipolar disorder type II. Thirty-two healthy adults and 15 adults with bipolar disorder type II underwent electroencephalography-based measurement of visual evoked potential plasticity and 3T magnetic resonance imaging of the brain at baseline and a follow-up brain scan on average 2.3 years later. The relationships between visual evoked potential plasticity at baseline and longitudinal cortical thickness changes were examined using Freesurfer and the Permutation Analysis of Linear Models tool. The analyses showed a negative association between the plasticity of the N1 visual evoked potential amplitude at baseline and thinning rate in the medial and lateral parietal and medial occipital cortices in healthy adults and in the right medial occipital cortex in the total sample of healthy adults and adults with bipolar disorder type II, indicating greater thinning over time in subjects with less N1 plasticity (pFWER < .05). Although preliminary, the results indicate an association between visual evoked potential plasticity and the future rate of cortical thinning in healthy adults and in bipolar disorder type II, supporting the hypothesis that cortical thinning might be related to synaptic dysfunction.

Stability and Change in Biopsychosocial Factors Associated With Fatigue 6 and 12 Months After Traumatic Brain Injury: An Exploratory Multilevel Study.

OBJECTIVE: To explore factors associated with stability and change in fatigue from 6 to 12 months following traumatic brain injury (TBI). SETTING: Combined in- and outpatient acute care and postacute rehabilitation settings. PARTICIPANTS: A total of 103 patients with confirmed intracranial injury were assessed 6 and/or 12 months following TBI. DESIGN: A prospective observational study with repeated measures at 2 time points, analyzed with a hybrid mixed-effects model. MAIN MEASURES: Primary outcomes were the fatigue factor derived from items from several fatigue patient-reported outcome measures (PROMs; Fatigue Severity Scale, Chalder Fatigue Scale, Giessen Subjective Complaints List-fatigue subscale, and Rivermead Post-Concussion Symptoms Questionnaire-fatigue item) Secondary outcomes were PROMs relating to pain, somatic and psychological distress, insomnia, sleepiness, personality traits, optimism, resilience, behavioral activation and inhibition, and loneliness, as well as neuropsychological measures. Demographic variables and injury severity characteristics were included as covariates. RESULTS: In multilevel regression, female sex, years of education, and 3 factors related to injury severity, somatic vulnerability, and psychosocial robustness were all significantly associated with variation in fatigue between subjects, and explained 61% of the variance in fatigue that was due to stable between-subject differences. Fatigue levels declined significantly over time. Changes in pain severity, somatic symptom burden, psychological distress, and behavioral inhibition were positively associated with changes in fatigue, explaining 22% of the variance in fatigue within subjects. CONCLUSIONS: The study demonstrated that several previously implicated factors show robust effects in distinguishing individuals with TBI on levels of fatigue, but only a few show additional within-subject associations across time. Pain severity, somatic symptom burden, psychological distress, and behavioral inhibition correlated with fatigue across time, implicating these factors as crucial targets for rehabilitation of patients with TBI who suffer from persistent fatigue.

Long term potentiation-like neural plasticity and performance-based memory function.

OBJECTIVE: Experience-dependent modulation of the visual evoked potential (VEP) has emerged as a promising non-invasive proxy for assaying long term potentiation (LTP)-like plasticity in the cerebral cortex. LTP is considered the principal candidate mechanism underlying learning and memory. There is, however, a paucity of evidence exploring associations between LTP-like plasticity and performance-based learning and memory. The present study aimed to explore the relationship between VEP-plasticity and higher-order learning and memory in healthy adults. METHOD: Visual and verbal learning and memory was assessed using the Aggie Figures Learning Test (AFLT) and the Rey Auditory Verbal Learning Test (RAVLT). The study included 111 healthy adults (61.1% females; mean age 37.6 years, range 17-71) who underwent a VEP paradigm employing visual high-frequency stimulation to induce a change in visual evoked responses recorded by scalp EEG. In addition, a more comprehensive neuropsychological assessment was administered. RESULTS: Several significant moderate age-corrected positive correlations were found between modulation of the later VEP components (N1 and P1-N1 peak-to-peak) and both visual and verbal learning and memory performance. Further, there were significant differences in learning and memory performance between participants showing a higher degree of modulation (>1 SD above mean) compared to participants showing a lower degree of modulation. No significant associations were found between VEP-plasticity and other neurocognitive domains. CONCLUSIONS: The current results suggest that LTP-like plasticity indexed by VEP modulation reflect processes specific to learning and memory. Future research is needed to further delineate the complex relationship between neural plasticity and learning and memory, specifically concerning possible clinical implications in populations with deficits in learning and memory function.

Self-reported cognitive impairment in cervical cancer survivors: A cross-sectional study.

OBJECTIVE: Cancer-related cognitive impairment (CRCI) is a major obstacle for cervical cancer survivors, preventing the return to their social life. This study assessed the prevalence of CRCI in cervical cancer survivors and studied the association of self-reported cognitive impairment with treatment regimen and the quality of life (QoL) domains depression, anxiety, and fatigue. METHODS: Six hundred twenty one cervical cancer survivors, treated with combined chemo-radiotherapy (CCRT) (n = 458) or surgery only (n = 163) were invited in this cross-sectional study. Self-reported cognitive function was assessed using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Fatigue and psychological distress were assessed using EORTC-QLQ C30 and Hospital Anxiety and Depression Scale (HADS). RESULTS: Data of 254 women (40.9%) was available for the analysis. Of those, 204 (80.3%) women had received CCRT and 50 (19.7%) surgery only. In the whole cohort, 42.5% reported significant cognitive impairment. In both treatment groups cognitive complaints were significantly associated with anxiety, depression, and fatigue (all p < 0.001). CCRT was strongly associated with increased risk of CRCI (OR = 4.02, 95% CI = 1.57-10.25). Anxiety, depression, and fatigue increased the risk of CRCI by 13% (OR: 1.13, 95% CI 1.03-1.23), 16% (OR 1.16, 95% CI 1.04-1.28) and 2% (OR 1.02, 95% CI 1.00-1.03), respectively. CONCLUSION: Almost half of the cervical cancer survivors after CCRT report significant cognitive impairment. CRCI is associated with other indicators of poor QoL, such as depression, anxiety and fatigue. An increased understanding of the specific cognitive domains affected and of the associated late effects like fatigue is crucial to customize successful interventions.

Do visual and auditory stimulus-specific response modulation reflect different mechanisms of neocortical plasticity?

Stimulus response modulation (SRM) of sensory evoked potentials represents a promising method as a non-invasive index of long-term potentiation (LTP)-like synaptic plasticity in the human sensory cortices. As of today, however, no consensus exists regarding which experimental parameters elicit the most robust SRM response. The aim of the current study was twofold; firstly, we aimed to replicate former studies demonstrating visual SRM in healthy adults. Second, we integrated visual and auditory stimuli within the same SRM recording session to assay potential cross-modal associations. Such an association between modalities would strengthen the assumption that the SRM effect reflects common mechanisms underlying synaptic plasticity rather than reflecting modality-specific phenomena. A replication of previous findings showing robust potentiation of the visual evoked potential was evident, supporting the majority of previous work using similar paradigms, lending further support to the notion that high-frequent visual stimulation is a viable probe into LTP-like synaptic plasticity in the human visual cortex. The auditory evoked potentials (AEPs) did not, however, fully replicate previous work, though a significant increase of temporally later AEP components was found. In contrast to our hypothesis, there were no significant within-subject cross-modality correlations between the visual and auditory SRM. This lack of significant association might suggest that auditory and visual SRM depend on different mechanisms, and that further SRM studies on non-invasive LTP-like synaptic plasticity should focus on optimizing paradigms within the visual modality.

Rehabilitation of executive function in chronic paediatric brain injury: a randomized controlled trial.

BACKGROUND: Impaired executive functions (EFs, i.e., purposeful, goal-directed behaviour) cause significant disability after paediatric acquired brain injury (pABI) warranting efficient interventions. Goal Management Training (GMT) is a metacognitive protocol proven effective for executive dysfunction in adults. This pre-registered, blinded, parallel-randomized controlled trial evaluated efficacy of a paediatric adaptation (pGMT) compared to a psychoeducative control (paediatric Brain Health Workshop, pBHW) to improve EF. METHODS: Children aged 10 to 17 years with pABI (e.g., traumatic brain injury, brain tumour), ≥ 1 year post-onset or ended treatment, with parent-reported EF complaints were eligible. Participants were randomized (computer-algorithm) to either group-based pGMT (n = 38) or pBHW (n = 38). The active control was tailored to keep non-specific factors constant. Thus, both treatments comprised of 7 sessions at hospitals over 3 consecutive weeks, followed by 4 weeks of telephone counselling of participants, parents, and teachers. Parent-reported daily life EF, assessed by the questionnaire Behavior Rating Inventory of Executive Function (BRIEF; Behavioral Regulation Index (BRI) and Metacognition Index (MI)), were co-primary outcomes 6 months post-intervention. Secondary outcomes included neuropsychological tests and a complex naturalistic task (Children's Cooking Task). RESULTS: Seventy-three participants (96%) completed allocated interventions and 71 (93%) attended the 6-month follow-up. The results demonstrated no significant difference in effectiveness for the two interventions on parent-reported EF: For BRIEFBRI, mean (SD) raw score for pGMT was 42.7 (8.8) and 38.3 (9.3) for pBHW. Estimated difference was - 2.3 (95% CI - 5.1 to 0.6). For BRIEFMI, the corresponding results were 80.9 (20.4) for GMT and 75.5 (19.3) for pBHW. Estimated difference was - 1.4 (95% CI -8.5 to 5.8). In performance-based tests, pGMT was associated with improved inhibition and executive attention, while pBHW was associated with fewer errors in the naturalistic task. CONCLUSIONS: In pABI, metacognitive training (pGMT) did not demonstrate additional effectiveness on parent-reported daily life EF at 6-month follow-up, when compared to a psychoeducative control. Both interventions were well-tolerated and demonstrated distinct improvements at different EF assessment levels. To conclude on pGMT efficacy, larger studies are needed, including further investigation of appropriate assessment levels and possible differences in effect related to treatment duration, developmental factors, and injury characteristics. TRIAL REGISTRATION: ClinicalTrials.gov , NCT0321534211, 11 July 2017.

Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors' sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

Social attainment in physically well-functioning long-term survivors of pediatric brain tumour; the role of executive dysfunction, fatigue, and psychological and emotional symptoms.

The purpose of this cross-sectional study was to investigate long-term social attainment in physically well-functioning adult survivors of pediatric brain tumour (PBT) and identify demographic, medical, and psychological factors related to poor social outcomes, with a special focus on the significance of executive dysfunction. One hundred and fourteen PBT survivors and a healthy control group provided personal data on social outcomes, i.e., education, work, and government benefits, and completed questionnaires on executive function (EF), psychological and emotional difficulties, and fatigue. A significantly higher number of survivors compared to healthy controls reported having received educational adjustments and substantial government benefits, and significantly more survivors than controls were currently not engaged in regular employment/training. PBT survivors and healthy controls did not differ on educational level or living situation. The factors most strongly associated with poor social outcomes were self-reported executive dysfunction, difficulties with adaptive functioning, and fatigue. The findings show that physically well-functioning PBT survivors are at risk of poorer social outcomes and financial dependence in adulthood compared to their healthy peers, and underline the importance of investigating EF in short- and long-term follow-ups. Future rehabilitation efforts should focus more on compensatory strategies for executive dysfunction and improving EF skills.

Social Perception Predicts Awareness of Illness in Persons With Schizophrenia.

Lack of clinical insight in patients with schizophrenia is an obstacle to optimal treatment. Social cognition is one of several variables central to insight deficits in schizophrenia. The aim of this study was to investigate clinical insight in relation to one domain of social cognition, social perception, while controlling for effects of nonsocial cognition and symptom severity. Clinical insight was measured in 55 patients with schizophrenia or schizoaffective disorder, using the Birchwood Insight Scale. Relationships across domains were used to assess social perception. Social perception predicted one of three subscales of clinical insight, "awareness of illness," and was the only unique contributor to this subscale. This indicates that social perception is linked to clinical insight through awareness of illness. More research is needed to fully understand the relationship between social and nonsocial cognition and symptoms in relation to clinical insight.

The Predictive Value of Depression in the Years After Heart Transplantation for Mortality During Long-Term Follow-Up.

OBJECTIVE: Current understanding of the prognostic impact of depression on mortality after heart transplantation (HTx) is limited. We examined whether depression after HTx is a predictor of mortality during extended follow-up. Subsequently, we explored whether different symptom dimensions of depression could be identified and whether they were differentially associated with mortality. METHODS: Survival analyses were performed in a sample of 141 HTx recipients assessed for depression, measured by self-report of depressive symptoms (Beck Depression Inventory - version 1A [BDI-1A]), at median 5.0 years after HTx, and followed thereafter for survival status for up to 18.6 years. We used uni- and multivariate Cox proportional hazard models to examine the association of clinically significant depression (BDI-1A total score ≥10), as well as the cognitive-affective and the somatic subscales of the BDI-1A (resulting from principal component analysis) with mortality. In the multivariate analyses, we adjusted for relevant sociodemographic and clinical variables. RESULTS: Clinically significant depression was a significant predictor of mortality (hazard ratio = 2.088; 95% confidence interval = 1.366-3.192; p = .001). Clinically significant depression also was an independent predictor of mortality in the multivariate analysis (hazard ratio = 1.982; 95% confidence interval = 1.220-3.217; p = .006). The somatic subscale, but not the cognitive-affective subscale, was significantly associated with increased mortality in univariate analyses, whereas neither of the two subscales was an independent predictor of mortality in the multivariate analysis. CONCLUSIONS: Depression measured by self-report after HTx is associated with increased mortality during extended follow-up. Clinical utility and predictive validity of specific depression components require further study.

Cognitive Effects of Perioperative Pregabalin: Secondary Exploratory Analysis of a Randomized Placebo-controlled Study.

BACKGROUND: Pregabalin has shown opioid sparing and analgesic effects in the early postoperative period; however, perioperative effects on cognition have not been studied. A randomized, parallel group, placebo-controlled investigation in 80 donor nephrectomy patients was previously performed that evaluated the analgesic, opioid-sparing, and antihyperalgesic effects of pregabalin. This article describes a secondary exploratory analysis that tested the hypothesis that pregabalin would impair cognitive function compared to placebo. METHODS: Eighty patients scheduled for donor nephrectomy participated in this randomized, placebo-controlled study. Pregabalin (150 mg twice daily, n = 40) or placebo (n = 40) was administered on the day of surgery and the first postoperative day, in addition to a pain regimen consisting of opioids, steroids, local anesthetics, and acetaminophen. Specific cognitive tests measuring inhibition, sustained attention, psychomotor speed, visual memory, and strategy were performed at baseline, 24 h, and 3 to 5 days after surgery, using tests from the Cambridge Neuropsychological Test Automated Battery. RESULTS: In the spatial working memory within errors test, the number of errors increased with pregabalin compared to placebo 24 h after surgery; median (25th, 75th percentile) values were 1 (0, 6) versus 0 (0, 1; rate ratio [95% CI], 3.20 [1.55 to 6.62]; P = 0.002). Furthermore, pregabalin significantly increased the number of errors in the stop-signal task stop-go test compared with placebo; median (25th, 75th percentile) values were 3 (1, 6) versus 1 (0, 2; rate ratio, 2.14 [1.13 to 4.07]; P = 0.020). There were no significant differences between groups in the paired associated learning, reaction time, rapid visual processing, or spatial working memory strategy tests. CONCLUSIONS: Perioperative pregabalin significantly negatively affected subdomains of executive functioning, including inhibition, and working memory compared to placebo, whereas psychomotor speed was not changed.

Theory of mind in schizophrenia and bipolar disorder: psychometric properties of the Norwegian version of the Hinting Task.

ABSTRACTIntroduction: The quality of measures used to assess theory of mind (ToM) in severe mental illness has not been sufficiently investigated. This study evaluated the psychometric properties of the Norwegian version of the Hinting Task in schizophrenia, bipolar I and II disorder and healthy controls.Methods: The study included 90 patients and 183 healthy controls. Internal consistency, ceiling effects, discriminatory power and concurrent and construct validity were investigated.Results: The Hinting Task displayed adequate levels of internal consistency for schizophrenia and bipolar I disorder. Ceiling effects emerged in all groups except the schizophrenia group. Schizophrenia patients scored significantly lower than all other groups, but no other significant group differences were detected. In the schizophrenia group, the Hinting Task's concurrent validity was substantiated by significant correlations with measures of neurocognition, symptoms and functional capacity. In the bipolar disorder groups, however, only a few significant relationships were found. Correlations between the Hinting Task and a measure of emotion recognition indicated that construct validity was higher for schizophrenia than bipolar disorder.Conclusions: The results suggest that the Norwegian Hinting Task is suited for use in schizophrenia research and assessment, but caution is warranted when using the test for other populations.

Electrophysiological characteristics in children with listening difficulties, with or without auditory processing disorder.

Objective: To determine if the auditory middle latency responses (AMLR), auditory late latency response (ALLR) and auditory P300 were sensitive to auditory processing disorder (APD) and listening difficulties in children, and further to elucidate mechanisms regarding level of neurobiological problems in the central auditory nervous system. Design: Three-group, repeated measure design. Study sample: Forty-six children aged 8-14 years were divided into three groups: children with reported listening difficulties fulfilling APD diagnostic criteria, children with reported listening difficulties not fulfilling APD diagnostic criteria and normally hearing children. Results: AMLR Na latency and P300 latency and amplitude were sensitive to listening difficulties. No other auditory evoked potential (AEP) measures were sensitive to listening difficulties, and no AEP measures were sensitive to APD only. Moderate correlations were observed between P300 latency and amplitude and the behavioural AP measures of competing words, frequency patterns, duration patterns and dichotic digits. Conclusions: Impaired thalamo-cortical (bottom up) and neurocognitive function (top-down) may contribute to difficulties discriminating speech and non-speech sounds. Cognitive processes involved in conscious recognition, attention and discrimination of the acoustic characteristics of the stimuli could contribute to listening difficulties in general, and to APD in particular.

Emotion perception, non-social cognition and symptoms as predictors of theory of mind in schizophrenia.

BACKGROUND: Theory of mind (ToM) can be divided into cognitive and affective ToM, and a distinction can be made between overmentalizing and undermentalizing errors. Research has shown that ToM in schizophrenia is associated with non-social and social cognition, and with clinical symptoms. In this study, we investigate cognitive and clinical predictors of different ToM processes. METHODS: Ninety-one individuals with schizophrenia participated. ToM was measured with the Movie for the Assessment of Social Cognition (MASC) yielding six scores (total ToM, cognitive ToM, affective ToM, overmentalizing errors, undermentalizing errors and no mentalizing errors). Neurocognition was indexed by a composite score based on the non-social cognitive tests in the MATRICS Consensus Cognitive Battery (MCCB). Emotion perception was measured with Emotion in Biological Motion (EmoBio), a point-light walker task. Clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Seventy-one healthy control (HC) participants completed the MASC. RESULTS: Individuals with schizophrenia showed large impairments compared to HC for all MASC scores, except overmentalizing errors. Hierarchical regression analyses with the six different MASC scores as dependent variables revealed that MCCB was a significant predictor of all MASC scores, explaining 8-18% of the variance. EmoBio increased the explained variance significantly, to 17-28%, except for overmentalizing errors. PANSS excited symptoms increased explained variance for total ToM, affective ToM and no mentalizing errors. DISCUSSION: Both social and non-social cognition were significant predictors of ToM. Overmentalizing was only predicted by non-social cognition. Excited symptoms contributed to overall and affective ToM, and to no mentalizing errors.

Normative data for diagnosing auditory processing disorder in Norwegian children aged 7-12 years.

OBJECTIVE: The main purpose of this research was to obtain normative data for auditory processing tests for Norwegian speaking children. DESIGN: Participants were administered routine audiological tests and an auditory processing test-battery consisting of Filtered Words, Competing Words, Dichotic Digits, Gaps In Noise, Duration- and Frequency Pattern, Binaural Masking Level Difference and HIST Speech in Noise test. A group of 10-year-old children were retested after two weeks. The effects ear, age and gender and the test-retest reliability were investigated. STUDY SAMPLE: There were 268 normal hearing children aged 7-12 years who participated in the study. RESULTS: Results revealed no differences between genders. The children showed improving performance by age on all tests, except from the Gaps In Noise and Binaural Masking Level Difference. As expected, the children showed a right ear advantage on dichotic speech tests that decreased with age. The test-retest reliability for the tests was good, with a small learning effect on the Filtered Words test. CONCLUSION: Normative data were established and the preferred tests for diagnosing Auditory Processing Disorder were suggested for Norwegian children aged 7-12 years.

Cognitive function after heart transplantation: Comparing everolimus-based and calcineurin inhibitor-based regimens.

BACKGROUND: Studies have shown conflicting results concerning the occurrence of cognitive impairment after successful heart transplantation (HTx). Another unresolved issue is the possible differential impact of immunosuppressants on cognitive function. In this study, we describe cognitive function in a cohort of HTx recipients and subsequently compare cognitive function between subjects on either everolimus- or calcineurin inhibitor (CNI)-based immunosuppression. METHODS: Cognitive function, covering attention, processing speed, executive functions, memory, and language functions, was assessed with a neuropsychological test battery. Thirty-seven subjects were included (everolimus group: n=20; CNI group: n=17). The extent of cerebrovascular pathology was assessed with magnetic resonance imaging. RESULTS: About 40% of subjects had cognitive impairment, defined as performance at least 1.5 standard deviations below normative mean in one or several cognitive domains. Cerebrovascular pathology was present in 33.3%. There were no statistically significant differences between treatment groups across cognitive domains. CONCLUSIONS: Given the high prevalence of cognitive impairment in the sample, plus the known negative impact of cognitive impairment on clinical outcome, our results indicate that cognitive assessment should be an integrated part of routine clinical follow-up after HTx. However, everolimus- and CNI-based immunosuppressive regimens did not show differential impacts on cognitive function.

Cognitive function among long-term survivors of heart transplantation.

BACKGROUND: Cognitive impairment is documented early after heart transplantation (HTx), but we lack data on cognitive function beyond the fourth year post-transplant. Against the background of good long-term survival, this knowledge is necessary to improve clinical care throughout the entire post-transplant period. METHODS: We assessed cognitive function with a neuropsychological test battery in a sample of HTx recipients ≥16 years post-transplant. To improve clinical utility, we also applied adapted consensus criteria for Mild Cognitive Impairment (MCI). Furthermore, we explored sociodemographic and clinical characteristics possibly related to cognitive function. RESULTS: Thirty-seven subjects were included 20.3 (±3.8) years after HTx. Mean age was 57.5 (±14.2) years, and 18.9% were women. Up to 38.9% exhibited impaired test performance (ie, performance at least 1.5 standard deviations below the normative mean) on several individual cognitive measures, especially on measures of processing speed, executive functions, memory, and language functions. One subject was diagnosed with dementia, and 30.1% qualified for MCI. Those with MCI had lower hemoglobin than those without. CONCLUSIONS: A substantial proportion of long-term survivors of HTx might be cognitively impaired. The level of impairment appears comparable to what is defined as MCI in the literature. Modifiable factors related to cognitive impairment might exist.

Neurocognitive and psychosocial function in children with benign external hydrocephalus (BEH)-a long-term follow-up study.

INTRODUCTION: Long-term impact of benign external hydrocephalus (BEH) on cognition is largely unknown, and indication for neurosurgical CSF diversion procedure is debated. This study reports neuropsychological and psychosocial function in operated and non-operated BEH children. METHODS: Eighty-six children (76 males) between 8 and 18 years (mean 13.9) diagnosed with BEH before 12 months were included, of whom 30.2 % were operated. Participants completed neuropsychological tests and questionnaires covering quality of life (PedsQL) and executive function (BRIEF). RESULTS: Both operated and non-operated BEH children performed significantly below normative means on several neuropsychological tests. The children scored themselves higher than the norm average on PedsQL; however, the parents reported life quality comparable to other children. Operated children performed poorer compared with non-operated children on tests of psychomotor speed, attention span, executive function, motor speed and coordination, and on the BRIEF subscale Monitoring. Operated children, but not their parents, reported more problems on PedsQL subscale School than non-operated children. DISCUSSION: Children with BEH display long-term subtle neurocognitive difficulties. Non-operated children performed significantly better on some neuropsychological measures and reported less psychosocial problems. This difference may be caused by a selection bias: neurosurgical intervention was more likely in children with clinically more pronounced symptoms.

Neurocognitive Outcome in Very Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia After Treatment with Chemotherapy Only.

BACKGROUND: There is a concern regarding long-term cognitive late effects after treatment for acute lymphoblastic leukemia (ALL). The present study assessed neuropsychological function in very long-term childhood ALL survivors treated with chemotherapy only. We also investigated associations between neurocognitive performance and individual treatment load. PROCEDURE: One-hundred and twelve adult ALL survivors, diagnosed 1970-2002 before age 16 and treated with chemotherapy only, and 100 comparison peers underwent neuropsychological tests covering processing speed, executive functions, working memory, and verbal learning and memory. Individual cumulative doses of cytostatic agents were extracted from the medical records for each patient. RESULTS: Mean age at diagnosis for survivors was 6.3 years and mean follow-up time was 22.6 years. There was no difference in general intellectual ability between survivors and comparison peers. However, survivors performed significantly more poorly in the neurocognitive domains' processing speed (P = 0.003, Cohen's d 0.48), executive functions, and working memory (both P < 0.001, Cohen's d 0.81-0.95). Among survivors, the rates of poor neurocognitive performance (>1.5 SD below control mean) for processing speed was 22%, executive functions 31%, working memory 34%, and verbal learning and memory 16%. Comparing survivors with poor versus normal neurocognitive performance, we found no difference with respect to cumulative doses of any of the cytostatic agents, age at diagnosis, or gender. CONCLUSIONS: Very long-term survivors of childhood ALL treated exclusively with chemotherapy showed no impairment in general intellectual ability, but significantly poorer performance in several neurocognitive domains than comparison peers. However, no associations emerged between neurocognitive impairment and treatment burden.