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Background Cognitive functioning is increasingly assessed as a secondary outcome in neuro-oncological trials. However, which cognitive domains or tests to assess, remains debatable. In this meta-analysis, we aimed to elucidate the longer-term test-specific cognitive outcomes in adult glioma patients. Methods A systematic search yielded 7098 articles for screening. To investigate cognitive changes in glioma patients and differences between patients and controls 1-year follow-up, random-effects meta-analyses were conducted per cognitive test, separately for studies with a longitudinal and cross-sectional design. A meta-regression analysis with a moderator for interval testing (additional cognitive testing between baseline and 1-year posttreatment) was performed to investigate the impact of practice in longitudinal designs. Results Eighty-three studies were reviewed, of which 37 were analyzed in the meta-analysis, involving 4078 patients. In longitudinal designs, semantic fluency was the most sensitive test to detect cognitive decline over time. Cognitive performance on mini-mental state exam (MMSE), digit span forward, phonemic and semantic fluency declined over time in patients who had no interval testing. In cross-sectional studies, patients performed worse than controls on the MMSE, digit span backward, semantic fluency, Stroop speed interference task, trail-making test B, and finger tapping. Conclusions Cognitive performance of glioma patients 1 year after treatment is significantly lower compared to the norm, with specific tests potentially being more sensitive. Cognitive decline over time occurs as well, but can easily be overlooked in longitudinal designs due to practice effects (as a result of interval testing). It is warranted to sufficiently correct for practice effects in future longitudinal trials.

Background: Cognitive training elicits mild-to-moderate improvements in cognitive functioning in people with multiple sclerosis (PwMS), although response heterogeneity limits overall effectiveness. Objective: To identify patient characteristics associated with response and non-response to cognitive training. Methods: Eighty-two PwMS were randomized into a 7-week attention training ( n = 58, age = 48.4 ± 10.2 years) or a waiting-list control group ( n = 24, age = 48.5 ± 9.4 years). Structural and functional magnetic resonance imaging (MRI) was obtained at baseline and post-intervention. Twenty-one healthy controls (HCs, age = 50.27 ± 10.15 years) were included at baseline. Responders were defined with a reliable change index of 1.64 on at least 2/6 cognitive domains. General linear models and logistic regression were applied. Results: Responders ( n = 36) and non-responders ( n = 22) did not differ on demographics, clinical variables and baseline cognition and structural MRI. However, non-responders exhibited a higher baseline functional connectivity (FC) between the default-mode network (DMN) and the ventral attention network (VAN), compared with responders ( p = 0.018) and HCs ( p = 0.001). Conversely, responders exhibited no significant baseline differences in FC compared with HCs. Response to cognitive training was predicted by lower DMN-VAN FC ( p = 0.004) and DMN-frontoparietal FC ( p = 0.029) (Nagelkerke R2 = 0.25). Conclusion: An intact pre-intervention FC is associated with cognitive training responsivity in pwMS, suggesting a window of opportunity for successful cognitive interventions.

Background Recent studies suggest a relationship between the APOE ε4 allele and cognitive outcome in patients treated for malignant brain tumors. Still, longitudinal investigations that include a pretreatment cognitive assessment are lacking and APOE’s effects in patients with benign tumors are understudied. This study investigated presurgical cognitive performance and postsurgical change in ε4‐carrying and non‐carrying patients with glioma and meningioma. Methods Neuropsychological test scores (CNS Vital Signs battery [seven measures], Digit Span Forward/Backward, Letter Fluency test) were obtained as part of a prospective study in which patients with meningioma and glioma underwent cognitive assessment 1 day before (T0, n = 505) and 3 (T3, n = 418) and 12 months after (T12, n = 167) surgery. APOE isoforms were identified retrospectively. ε4 carriers and non‐carriers were compared with regard to pretreatment cognitive performance on the group and individual level. Changes in performances over time were compared with longitudinal mixed model analysis in the total sample and the subgroup receiving adjuvant treatment. Results Carriers and non‐carriers did not differ with regard to pretreatment performance. No significant main effect of ε4 carrier status or interaction between time (T0–T12) and carrier status was found on any of the tests in the whole sample nor in the sample receiving adjuvant treatment. Conclusions This study found no evidence of increased vulnerability for pretreatment cognitive dysfunction or cognitive decline within 1 year after surgery in APOE ε4‐carrying meningioma and glioma patients. Investigations that include larger samples at longer‐term follow‐up are recommended to investigate potential late treatment effects., This prospective longitudinal study found no evidence for worse pretreatment cognitive function in APOE ε4‐carrying as compared to non‐carrying primary brain tumor patients. Cognitive performances over time up to 12 months after surgery also showed no statistically significant differences between carriers and non‐carriers. APOE ε4’s effects on cognition should be further studied in large primary brain tumor samples with long‐term follow‐ups, where possible interactions with other genetic, clinical and behavioral factors should also be investigated.

BackgroundSurvival rates have improved in the past years for patients with brain metastases (BMs).ObjectiveTo evaluate cognitive functioning and health-related quality of life (HRQoL) after Gamma Knife radiosurgery (GKRS) in a relatively large sample of long-term survivors.MethodsData from 38 long-term survivors (assessments available ≥ 12 mo post-GKRS) with, at time of enrollment, 1 to 10 newly diagnosed BMs, expected survival > 3 mo, and Karnofsky Performance Status ≥ 70 were analyzed. Cognitive functioning and HRQoL were assessed pre-GKRS (n = 38) and at 3 (n = 38), 6 (n = 37), 9 (n = 37), 12 (n = 34), 15 (n = 28), and 21 (n = 21) mo post-GKRS. The course of cognitive test performance and of HRQoL over time was analyzed using linear mixed models. Individual changes in cognitive performance and HRQoL from pre-GKRS to 21 mo were determined using reliable change indexes (RCIs) and clinical meaningful cutoffs, respectively.ResultsCognitive performances and HRQoL of long-term survivors remained stable or improved up to 21 mo after GKRS. Improvements were found for immediate and delayed verbal memory, working memory, information processing speed, and emotional well-being. On the individual level, most patients had stable or improved test performances or HRQoL. For physical well-being only, most patients (47.6%) showed a decline (vs 28.6% improvement or 23.8% no change) from pre-GKRS until 21 mo post-GKRS.ConclusionUp to 21 mo after GKRS, cognitive functioning and overall HRQoL improved or remained stable in long-term survivors. In long-term survivors with 1 to 10 BMs, GKRS did not cause (additional) cognitive deteriorations or declines in HRQoL at longer-term follow-up.

Purpose Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients’ health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1–10 BM over time. Methods A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes. Results At group level, patients’ physical well-being worsened, whereas emotional well-being improved over 9 months. Scores on other HRQoL subscales did not change significantly. Number (1–3 versus 4–10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9 months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects. Conclusion Our results indicate that even in patients with up to 10 BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level. Trail registration number ClinicalTrials.gov Identifier: NCT02953756, November 3, 2016.

Background Evidence-based cognitive rehabilitation programs for brain tumor patients are not widely available, despite the high need. We aimed to evaluate the effects of a tablet-based cognitive rehabilitation program on cognitive performance, cognitive complaints, fatigue, and psychological distress in primary brain tumor patients following neurosurgery. Also, attrition, adherence and patient satisfaction with the program were evaluated. Methods Adults with presumed low-grade glioma and meningioma were recruited before surgery. Three months thereafter, participants were allocated to the intervention group or waiting-list control group using minimization. The 10-week eHealth app ReMind, based on the effective face-to-face intervention, consisted of psychoeducation, strategy-training and attention retraining. Performance-based cognitive outcomes and patient-reported outcomes were assessed before surgery and 3, 6 and 12 months thereafter. Mean scores, percentages of cognitively impaired individuals and reliable change indices (RCIs) were compared between groups. Results Sixty-two out of 183 eligible patients were randomized. Of the people who declined, 56% reported that participation would to be too burdensome. All participants found a tablet-app suitable for delivery of cognitive rehabilitation and 90% rated the program as “good” or “excellent”. Performance-based cognitive outcomes and patient-reported outcomes did not significantly differ in group means over time nor RCIs between the intervention (final n = 20) and control group (final n = 25). Conclusions Recruitment at this early stage was difficult, resulting in limited statistical power. No significant effects were demonstrated, while adherence and satisfaction with the eHealth program were good. In clinical practice, ReMind may be helpful, if timing would be adapted to patients’ needs.

BackgroundPre- and postoperative cognitive deficits have repeatedly been demonstrated in patients with glioblastoma (GBM).ObjectiveTo identify presurgical risk factors that facilitate the identification of GBM patients at risk for postoperative cognitive impairment.MethodsPatients underwent neuropsychological assessment using Central Nervous System Vital Signs 1 d before (T0) and 3 mo after surgery (T3). Patients’ standardized scores on 7 cognitive domains were compared to a normative sample using one-sample z tests. Reliable change indices with correction for practice effects were calculated to assess cognitive changes in individual patients over time. Logistic regression models were performed to assess presurgical sociodemographic, clinical, psychological, and cognitive risk factors for postoperative cognitive impairments.ResultsAt T0, 208 patients were assessed, and 136 patients were retested at T3. Patients showed significantly lower performance both prior to and 3 mo after surgery on all cognitive domains compared to healthy controls. Improvements and declines over time occurred respectively in 11% to 32% and 6% to 26% of the GBM patients over the domains. The regression models showed that low preoperative cognitive performance posits a significant risk factor for postoperative cognitive impairment on all domains, and female sex was a risk factor for postoperative impairments in Visual Memory.ConclusionWe demonstrated preoperative cognitive risk factors that enable the identification of GBM patients who are at risk for cognitive impairment 3 mo after surgery. This information can help to inform patients and clinicians at an early stage, and emphasizes the importance of recognizing, assessing, and actively dealing with cognitive functioning in the clinical management of GBM patients.

Objective:This study aimed to examine: (1) patient–proxy agreement on executive functioning (EF) of patients with primary brain tumors, (2) the relationships between patient- and proxy-report with performance-based measures of EF, and (3) the potential influence of performance-based measures on the level of agreement.Methods:Meningioma and low-grade glioma patients and their informal caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF-A) 3 months after surgery. The two index scores of the BRIEF-A, Behavioral Regulation and Metacognition, were evaluated. Mean scores of patients and proxies were compared with normative values and with each other. Patient–proxy agreement was evaluated with Lin’s concordance correlation coefficients (CCCs) and Bland–Altman plots. Pearson correlation coefficients between reported EF and performance-based measures of EF were calculated. Multiple regression analysis was used to evaluate the potential influence of test performance on differences in dyadic reports.Results:A total of 47 dyads were included. Patients reported significantly more problems on the Metacognition Index compared to norms, and also in comparison with their proxies. Effect sizes indicated small differences. Moderate to substantial agreement was observed between patients and proxies, with CCCs of 0.57 and 0.61 for Metacognition and Behavioral Regulation, respectively. Correlations between reported EF and test performance ranged between −0.37 and 0.10. Dyadic agreement was not significantly influenced by test performance.Conclusions:Patient–proxy agreement was found to be moderate. No clear associations were found between reported EF and test performance. Future studies should further explore the existing and new methods to assess everyday EF in brain tumor patients.

BackgroundFatigue is a common symptom in patients with brain tumors, but comprehensive studies on fatigue in patients with meningioma specifically are lacking. This study examined the prevalence and correlates of fatigue in meningioma patients.MethodsPatients with grade I meningioma completed the Multidimensional Fatigue Inventory (MFI-20) before and 1 year after neurosurgery. The MFI consists of 5 subscales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation, and Reduced Activity. Patients’ scores were compared with normative data. Preoperative fatigue was compared with postoperative fatigue. Correlations with sex, age, education, tumor hemisphere, preoperative tumor volume, antiepileptic drugs (AEDs), symptoms of anxiety/depression, and self-reported cognitive complaints were explored.ResultsQuestionnaires were completed by 65 patients preoperatively, and 53 patients postoperatively. Of 34 patients, data from both time points were available. Patients had significantly higher fatigue levels on all subscales compared to normative values at both time points. Mean scores on General Fatigue, Physical Fatigue, and Mental Fatigue remained stable over time and improvements were observed on Reduced Motivation and Reduced Activity. Preoperatively, the prevalence of high fatigue (Z-score ≥ 1.3) varied between 34% for Reduced Motivation and 43% for General Fatigue/Mental Fatigue. The postoperative prevalence ranged from 19% for Reduced Activity to 49% on Mental Fatigue. Fatigue was associated with cognitive complaints, anxiety and depression, but not with education, tumor lateralization, tumor volume, or AEDs.ConclusionFatigue is a common and persistent symptom in patients with meningioma undergoing neurosurgery. Findings emphasize the need for more research and appropriate care targeting fatigue for meningioma patients.

PurposeA growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS.MethodsWe searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately.ResultsOut of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used.ConclusionsIn general, SRS does not have significant negative effects on patients’ overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review.

Purpose of review: Increased life expectancy in brain tumour patients had led to the need for strategies that preserve and improve cognitive functioning, as many patients suffer from cognitive deficits. The tumour itself, as well as antitumor treatment including surgery, radiotherapy and chemotherapy, supportive treatment and individual patient factors are associated with cognitive problems. Here, we review the recent literature on approaches that preserve and improve cognitive functioning, including pharmacological agents and rehabilitation programs. Recent findings: Minimizing cognitive dysfunction and improving cognitive functioning in brain tumour patients may be achieved both by preserving cognitive functioning during antitumor treatment, including techniques such as awake brain surgery, less invasive radiation therapies such as stereotactic radiotherapy and proton therapy, as well as with interventions including cognitive rehabilitation programmes. Novel rehabilitation programs including computer-based cognitive rehabilitation therapy (CRT) programmes that can be adjusted to the specific patient needs and can be administered at home are promising. Furthermore, personalized/precision medicine approaches to identify patients who are at risk for cognitive decline may facilitate effective treatment strategies in the future. Summary: Cognitive functioning has gained greater awareness in the neuro-oncological community, and methods to preserve and improve cognitive functioning have been explored. Rehabilitation programmes for brain tumour patients should be further developed and referred to in clinical practice.

Purpose Progressive disease in patients with high-grade glioma may be reflected in cognitive decline. However, the cognitive functions most sensitive to progression may differ between patients. We investigated whether decline on a personalized selection of tests predicted progressive disease according to RANO criteria in high-grade glioma patients. Methods Starting one day before surgery, patients underwent neuropsychological assessment every three months during standard treatment and clinical follow-up. We first made a personalized selection of three tests that showed the highest Reliable Change Index (RCI) values, i.e., most positive change, at the first post-surgical assessment for each patient. In subsequent follow up, a decline of RCI ≤ − 1 on at least two of the three tests in the selection was considered cognitive decline. We performed a discrete Cox proportional hazards model including a time-dependent coefficient cognitive decline (vs. stability) and covariate age to predict progressive disease. Results Twenty five patients were included. Cognitive decline on the personalized test selection preceded or had occurred by the time progression was established in 9/15 patients with RANO confirmed progressive disease (60%). Decline was absent in 8/10 patients (80%) with stable disease during participation. The independent hazard ratio for progression in case of cognitive decline was 5.05 (p < 0.01) compared to stable performance. Conclusions Using only three patient-specific neuropsychological tests, we found a fivefold increased chance of disease progression in case of cognitive decline as compared to stable performance. Brief, patient-tailored cognitive assessment may be a noninvasive addition to disease monitoring without overburdening patients and clinical care.

Aims: Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS).Materials and methods: Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated.Results: At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients).Conclusions: Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.

Purpose Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients’ health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1–10 BM over time. Methods A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes. Results At group level, patients’ physical well-being worsened, whereas emotional well-being improved over 9 months. Scores on other HRQoL subscales did not change significantly. Number (1–3 versus 4–10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9 months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects. Conclusion Our results indicate that even in patients with up to 10 BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level. Trail registration number ClinicalTrials.gov Identifier: NCT02953756, November 3, 2016.

Purpose Fatigue is a common and distressing symptom in cancer patients which negatively affects patients’ daily functioning and health-related quality of life. The aim of this study was to assess multidimensional fatigue in patients with brain metastases (BM) before, and after Gamma Knife radiosurgery (GKRS). Methods Patients with BM, an expected survival > 3 months, and a Karnofsky Performance Status ≥ 70 and 104 Dutch non-cancer controls were recruited. The Multidimensional Fatigue Inventory (MFI), measuring general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation, was used. Baseline levels of fatigue between patients and controls were compared using independent-samples t-tests. The course of fatigue over time, and clinical and psychological predictors thereof, were analyzed using linear mixed models (within-group analyses). Results Ninety-two, 67 and 53 patients completed the MFI at baseline, and 3 and 6 months after GKRS. Before GKRS, patients with BM experienced significantly higher levels of fatigue on all subscales compared to controls (medium to large effect sizes). Over 6 months, general and physical fatigue increased significantly (p = .009 and p

Objective The majority of meningioma patients suffer from presurgical cognitive deficits. Since meningiomas do not directly damage the brain, this is presumably caused by a functional integrity reduction of the surrounding brain tissue through perilesional edema and/or mass effect of the tumor. Tumor location is a key feature in determining neurological symptoms in brain tumor patients, but the relationship between meningioma location and cognitive performance remains unclear. This study aimed to identify brain areas where the presence of a meningioma forms a potential risk factor for worse cognitive performance as compared to meningiomas at other locations. Method Neuropsychological data (CNS Vital Signs) and MRI were collected in 224 meningioma patients one day before surgery. Sociodemographically corrected scores were calculated for 7 cognitive domains. Tumors were semiautomatically segmented and mapped into MNI-space for use in Statistical Region of Interest analyses. For each cognitive domain, we tested whether larger proportions of tumor overlap with each of the 150 defined regions were associated with worse performance. Results After multiple comparison (Bonferroni) and lesion volume correction, larger proportions of tumor overlap with both the left middle and superior frontal gyrus were associated with worse complex attention scores. Larger proportions of tumor overlap with the left middle frontal gyrus were associated with worse cognitive flexibility scores. For the other domains, no association between tumor overlap with a region and cognitive performance was found. Conclusions The current results suggest that, compared to patients with a meningioma at other locations, patients with a meningioma at the left middle frontal gyrus are at potential risk for worse performance on cognitive flexibility and complex attention whereas patients with a meningioma at the left superior frontal gyrus are at potential risk for worse performance on complex attention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: Although meningioma patients show deficits in objective cognitive functioning (OCF) measured with neuropsychological tests, subjective cognitive functioning (SCF) has received little attention. We investigate SCF from pre- to post-surgery and its associations with OCF, psychological, sociodemographic, and clinical characteristics.Methods: SCF was measured using the Cognitive Failures Questionnaire (CFQ) one day before (T0), and three (T3) and twelve months (T12) after surgery. Patients' scores were compared to normative data and changes over time were assessed. The neuropsychological battery CNS Vital Signs and the Hospital Anxiety and Depression Scale were administered. Correlations of SCF with OCF, psychological, sociodemographic, and clinical characteristics were explored.Results: Patients reported significantly better SCF as compared with controls at T0 (N=54) and T3 (N=242), but not at T12 (N=50). A significant decrease in group level SCF was observed from T0 to T12 (n=24, pConclusions: Meningioma patients experienced better SCF as compared to controls before and three months after surgery, which might be the result of phenomena related to disease and recovery. As the findings suggest that cognitive symptoms might increase later on, future studies should further investigate the course of SCF in meningioma patients. In clinical practice, measurements of SCF should be combined with those of OCF and psychological distress in order to determine whether and which interventions are needed.

Background Meningioma patients are known to face cognitive deficits before and after surgery. We examined individual changes in cognitive performance over time and identified preoperative predictors of cognitive functioning 12 months after surgery in a large sample of meningioma patients. Methods Patients underwent neuropsychological assessment (NPA) using CNS Vital Signs 1 day before (T0) and 3 (T3) and 12 (T12) months after surgery. Patients’ sociodemographically corrected scores on 7 cognitive domains were compared with performance of a normative sample using one-sample z tests and chi-square tests of independence. Reliable change indices with correction for practice effects were calculated for individual patients. Linear mixed effects models were used to identify preoperative predictors of performance at T12. Results At T0, 261 patients were assessed, and 229 and 82 patients were retested at T3 and T12, respectively. Patients showed impaired cognitive performance before and after surgery, and although performance improved on the group level, cognitive scores remained significantly lower than in the normative sample up to T12. On the individual level, performance remained stable in the majority of patients. Better preoperative performance, younger age, male sex, and higher educational level predicted better late cognitive performance. Conclusions Meningioma patients face serious and persistent pre- and postsurgical cognitive deficits. A preoperative NPA together with sociodemographic characteristics may provide valuable information on the late cognitive outcome of individual meningioma patients. These results can help to inform patients and clinicians on late cognitive outcomes at an early stage, and emphasizes the importance of presurgical NPA and timely cognitive rehabilitation.

Background: Many patients with primary brain tumors suffer from cognitive deficits, which negatively impact their quality of life. However, cognitive rehabilitation programs for these patients are scarce. We developed an iPad-based cognitive rehabilitation program for brain tumor patients, which was based on our effective face-to-face cognitive rehabilitation program. After successful completion of a feasibility study, a randomized controlled trial has been started.Objective: To evaluate the immediate and long-term effects of the iPad-based program on cognitive performance and patient-reported outcome measures (PROMs) in patients with primary brain tumors in an early stage of the disease.Methods: Prior to surgery, patients with presumed low-grade glioma and meningioma are included. Before surgery and 3 mo after surgery, neuropsychological assessments are conducted. After the second neuropsychological assessment, patients are assigned to the intervention group or waiting-list control group. The intervention consists of psychoeducation,compensation training, and retraining. Patients are advised to spend 3 h perweek on the program for 10 wk. Immediately after completion of the program and a halfyear thereafter, postintervention assessments take place. Patients in the control group are offered the opportunity to follow the program after all study assessments.Expected outcomes: We expect that early cognitive rehabilitation has beneficial effects on cognitive performance and PROMs in brain tumor patients.Discussion: The iPad-based program allows brain tumor patients to follow a cognitive rehabilitation program from their homes. Forthcoming results may contribute to further improvement of supportive care for brain tumor patients.

This study examined test-retest reliabilities and (predictors of) practice effects of the widely used computerized neuropsychological battery CNS Vital Signs. The sample consisted of 158 Dutch healthy adults. At 3 and 12 months follow-up, 131 and 77 participants were retested. Results revealed low to high test-retest reliability coefficients for CNS VS' test and domain scores. Participants scored significantly higher on the domains of Cognitive Flexibility, Processing Speed, and Reaction Time at the 3-month retest. No significant differences in performance were found over the second interval. Age, education, and retest-interval were not significantly associated with practice effects. These results highlight the need for methods that evaluate performance over time while accounting for imperfect test-retest reliabilities and practice effects. We provided RCI-formulae for determining reliable change, which may be possible solution for future work facing the methodological issues of retesting.Public Significance StatementImperfect test-retest reliability and practice effects must be taken into account when interpreting change in neuropsychological test scores over time, for example by applying RCI-formulae for the determination of reliable change.

Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as “good” or “excellent”. All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients’ feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

Introduction: Central Nervous System Vital Signs (CNS VS) is a computerized neuropsychological battery that is translated into many languages. However, published CNS VS’ normative data were established over a decade ago, are solely age-corrected, and collected in an American population only. Method: Mean performance of healthy Dutch participants on CNS VS was compared with the original CNS VS norms (N = 1,069), and effects of sociodemographic variables were examined. Results:z tests demonstrated no significant differences in performance on four out of seven cognitive domains; however, Dutch participants (N = 158) showed higher scores on processing and psychomotor speed, as well as on cognitive flexibility. Although the original CNS VS norms are solely age-corrected, effects of education and sex on CNS VS performance were also identified in the Dutch sample. Discussion: Users should be cautious when interpreting CNS VS performance based on the original American norms, and sociodemographic factors must also be considered.

BACKGROUND Patients with lower grade (2 and 3) gliomas (LrGG) are living longer, but often with cognitive impairments from their tumor and treatments. However, cognitive assessments and access to cognitive rehabilitation are not a standard part of care. We present preliminary results of a pilot study investigating feasibility and efficacy of three cognitive rehabilitation strategies for stable LrGG patients – in-person manualized cognitive rehabilitation; iPad based cognitive rehabilitation program of retraining and compensation strategies (ReMind); or daily instructional text messages (Healthy SMS). METHODS Eligible patients were adults with clinically and radiologically stable LrGG, > 6 months from last treatment, and ≥1 standard deviation (SD) below normal on ≥ 2 domains of neuropsychological assessments. Patients were first offered in-person cognitive rehabilitation or randomized to ReMind or Healthy SMS if unable to attend in-person. Interventions lasted 3 months. Neuropsychological and HRQOL assessments, using PROMIS NeuroQOL, were conducted at baseline, 3, and 6 months post-intervention. Feasibility was defined as attending ≥80% of in-person sessions; completing ≥80% of ReMind tasks; or not opting out of Healthy SMS texts. RESULTS To date 23/60 patients have enrolled: 11 in-person and 12 randomized to ReMind (5) or Healthy SMS (7). Demographic and clinical characteristics were similar between cohorts. Median age at testing was 46 years, with 65% female, and 78% having received prior radiation (median 4.1 years, range 3.2 – 11.5). At baseline, processing speed was the most common domain of impairment with 43% ≥ 1.5 SD below normal and 36% patients reporting subjective cognitive impairment on HROQL assessment. Feasibility was 71% for in-person rehabilitation; 50% for ReMind; and 100% for Health SMS. CONCLUSION These preliminary results demonstrate that stable LrGG patients with subjective and objective cognitive impairments can reasonably engage in cognitive rehabilitation interventions. Updated data including post-intervention neuropsychological and HROQL related changes will be presented.

Purpose Cognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic. Methods Newly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances. Results 114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm3, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance. Conclusion These findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification.

Many patients with cancer develop cognitive dysfunction due to their cancer and/or adverse effects of their cancer therapy. Cognitive dysfunction can adversely impact many aspects of patients’ lives including decreasing functional independence, reducing competitive employment, and contributing to role limitations within family and social communities. These deficits and accompanying losses frequently contribute to reductions in quality of life. Recently, increased effort has been directed to investigating therapeutic and rehabilitative approaches to prevent cognitive decline, manage cognitive deficits or restore cognitive function, enhance patient quality of life, increase functional independence, and reduce caregiver burden. Nonpharmacologic intervention approaches examined thus far have included compensatory strategy training, cognitive retraining, physical exercise, relaxation and other symptom management approaches, and biofeedback. At present, the evidence is stronger for these interventions to enhance subjective compared to objective cognitive functioning. Very few of these studies have integrated neuroimaging outcomes to more directly investigate the treatment effects on the brain.

Background Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs). Methods Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20–45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months. Results The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health–related quality of life. Conclusions This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients.

OBJECTIVEThe authors evaluated the cognitive performance of patients with low-grade glioma (LGG) before and after surgery, and specifically investigated 1) the effects of hemispheric tumor location and 2) the type of surgery (either with or without intraoperative stimulation mapping [ISM]).METHODSPatients underwent neuropsychological assessment 1 day before (T0) and 3 months after (T3) surgery. ISM targeted motor and/or language functions, but no other cognitive functions. Using 2-way mixed ANOVAs, differences between groups (i.e., for patients with right- vs left-sided lesions and normative controls [NCs], and also for patients operated on with vs without ISM and NCs), effects over time (T0–T3), and interaction effects in cognitive functioning were explored. Individual changes over time were assessed with reliable change indices for each neuropsychological test.RESULTSIn total, 77 patients with LGG were included (38 and 39 patients with right- and left-sided lesions, respectively; and 42 patients with and 35 patients without ISM). The majority of patients who were operated on with ISM had left-sided lesions. Patients with right- and left-sided lesions scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. No significant differences between hemispheric groups were found at T0 or at T3. Patients with left-sided lesions showed significant deterioration of performance on verbal memory and sustained attention over time. Patients who underwent operation with versus without ISM scored significantly lower on 6 and 3 out of 8 tests, respectively, compared to NCs. Patients in the ISM group scored significantly lower on the Stroop test, shifting attention test, and verbal fluency test than patients without ISM. Also, the ISM group showed a significant decline in mean cognitive flexibility and sustained attention performance over time.CONCLUSIONSCognitive impairments were found in patients irrespective of hemispheric tumor location, whereby patients who were operated on with ISM performed slightly worse after surgery than patients without ISM. The authors conclude that there is room for improvement of cognitive functioning in surgically treated patients with LGG. The use of specific tests for higher cognitive functions during surgery may potentially improve functional outcome, but that is to be determined in future studies and balanced against oncological outcome. Implementation of neuropsychological assessments into the clinical management of patients with LGG should be encouraged, to inform and alert patients and clinicians on the status of cognitive functioning.

Introduction: Many patients with brain cancer experience cognitive problems. In this narrative review, we comprehensively evaluated empirical studies on various intervention approaches for cognitive problems in these patients. Methods: Intervention studies that reported effects on cognitive functioning (either objectively tested or subjectively reported) in adult patients with primary and/or secondary brain tumours were identified through online searches in PubMed (MEDLINE) and Web of Science up to 13 March 2019. Results: Of the 364 identified records, 10 pharmacological (including five randomised placebo-controlled trials), 10 cognitive rehabilitation (including five [pilot] RCTs) and two multiple-group exercise studies matched the inclusion criteria. Seventeen of 22 studies had final sample sizes smaller than 40. Several cognitive rehabilitation studies and some pharmacological approaches (donepezil and memantine) showed (at least partial) benefits for cognitive problems in adults with brain cancer. The effects of other pharmacological and exercise interventions were inconclusive and/or preliminary. Conclusions: Overall, drawing firm conclusions is complicated due to various methodological shortcomings, including the absence of a (placebo) control group and small sample sizes. Promising effects have been reported for cognitive rehabilitation and some pharmacological approaches. Suggestions for more thorough research with respect to the various approaches are provided.

OBJECTIVEPatients with nonfunctioning pituitary adenomas (NFPAs) can suffer from cognitive dysfunction. However, the literature on longitudinal cognitive follow-up of patients undergoing endoscopic endonasal transsphenoidal surgery (EETS) is limited. This study was performed to investigate perioperative cognitive status and course in patients with NFPAs.METHODSPatients underwent computerized neuropsychological assessment 1 day before (n = 45) and 3 months after (n = 36) EETS. Performance in 7 domains was measured with a computerized test battery (CNS Vital Signs) and standardized using data from a healthy control group. The authors conducted analyses of cognitive performance at both time points and changes pre- to post-ETSS on a group and an individual level. Linear multiple regression analyses were employed to investigate predictors of cognitive performance.RESULTSOn average, patients scored significantly lower in 6 of 7 cognitive domains before and after surgery than controls. Impairment proportions were significantly higher among patients (56% before surgery, 63% after surgery) than among controls. Patients showed no change over time in group-level (mean) performance, but 28% of individual patients exhibited cognitive improvement and 28% exhibited cognitive decline after surgery. Hormonal deficiency showed a positive correlation with verbal memory before surgery. Postoperative performances in all cognitive domains were predicted by preoperative performances.CONCLUSIONSCognitive impairment was present before and after EETS in over half of NFPA patients. Individual patients showed diverse postoperative cognitive courses. Monitoring of cognitive functioning in clinical trajectories and further identification of disease-related and psychological predictors of cognition are warranted.

Purpose Information on health-related quality of life (HRQoL) of patients with brain metastases (BM) before stereotactic radiosurgery (SRS) is very relevant to improve communication between patients and clinicians and to be able to interpret changes in HRQoL after SRS. The aim of this study was to evaluate the prevalence and severity of complaints on different aspects of pre-SRS HRQoL among patients with BM and to identify predictors thereof. Methods Patients with 1–10 newly diagnosed BM, expected survival > 3 months, Karnofsky Performance Status ≥ 70, and scheduled to undergo SRS were included. HRQoL was measured with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. One-sample z-tests were conducted to analyze differences between patients with BM and published normative data of a general adult sample and of an adult cancer sample. Multiple regression analyses were run to identify predictors of pre-SRS HRQoL. Results On the individual level, most patients with BM (57.6% of 92 included patients) reported complaints regarding emotional well-being. As a group, patients with BM reported significantly lower emotional well-being compared to both control groups and significantly higher social well-being compared to the general population. Worse psychological factors, e.g. physical fatigue, depression, mental fatigue and anxiety, predicted aspects of pre-SRS HRQoL. Conclusions An increased understanding of pre-SRS HRQoL and predictors hereof, provides us with more insight into the well-being of our patients with BM and is necessary for the interpretation of (changes in) HRQoL after SRS. Electronic supplementary material The online version of this article (10.1007/s11060-019-03186-z) contains supplementary material, which is available to authorized users.

OBJECTIVE: To assess feasibility and effect on cognitive function and Health-Related Quality of Life (HRQoL) of an iPad-based intervention in grade 2 and 3 glioma patients stable off treatment. Patients with lower grade glioma suffer significant cognitive dysfunctions that impact their HRQoL. Formal cognitive rehabilitation is a limited resource that may be more available if deployed with a mobile device such as an iPad. METHODS: Stable, grade 2 and 3 glioma patients with subjective cognitive complaints, complete a baseline computerized battery of standardized cognitive tests using the NIH Toolbox and HRQOL assessment with the FACT-BR. Patients then completed a novel, evidence-based, iPad based, brain tumor specific, cognitive rehabilitation program called ReMind over the next 3 months (~3 hours per week). NIH Toolbox and HRQOL assessments were repeated after completion of the rehabilitation, and again 9 months after baseline. Primary endpoint was feasibility with secondary endpoints of changes in cognitive scores and HRQOL assessments. RESULTS: To date, 10 patients have enrolled and completed baseline testing, of whom 5 have completed ReMind rehabilitation. Median age is 56 years. Median disease duration is 7.6 years. 5 patients have Oligodendrogliomas (IDH mutated and 1p19q deleted), 3 patients have Astrocytomas, IDH mutated, and 2 patients have Astrocytomas NOS. 5 are grade II and 5 are grade III. 5 had left hemisphere tumors, 4 had right hemisphere tumors, and 1 was bilateral. 10 had prior chemotherapy and 8 prior radiation. We anticipate enrolling another 5 – 10 patients and will present the updated feasibility data as well as changes in cognitive and HRQOL scores. CONCLUSION: As patients with lower grade tumors live longer, it is important to increase availability of cognitive interventions to improve HRQOL and outcomes. This iPad based approach provides in-home access to cognitive training and compensation strategies for patients with brain tumors.

Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11–20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups. The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717 , first received October 27, 2016, 8 patients were enrolled in this study on 31 July 2017.

Objective:In this pilot study, we investigated the feasibility of a home-based, remotely guided exercise intervention for patients with gliomas.Design:Pilot randomized controlled trial (RCT) with randomization (2:1) to exercise or control group.Subjects:Patients with stable grade II and III gliomas.Intervention:The six-month intervention included three home-based exercise sessions per week at 60%–85% of maximum heart rate. Participants wore heart rate monitors connected to an online platform to record activities that were monitored weekly by the physiotherapist.Main measures:Accrual, attrition, adherence, safety, satisfaction, patient-reported physical activity, VO2 peak (by maximal cardiopulmonary exercise testing) and body mass index (BMI) at baseline and at six-month follow-up.Results:In all, 34 of 136 eligible patients (25%) were randomized to exercise training (N = 23) or the control group (N = 11), of whom 19 and 9, respectively, underwent follow-up. Mean adherence to prescribed sessions was 79%. Patients’ experiences were positive. There were no adverse events. Compared to the control group, the exercise group showed larger improvements in absolute VO2 peak (+158.9 mL/min; 95% CI: −44.8 to 362.5) and BMI (−0.3 kg/m²; 95% CI: −0.9 to 0.2). The median increase in physical activity was 1489 metabolic equivalent of task (MET) minutes higher in the exercise group. The most reported reasons for non-participation were lack of motivation or time.Conclusion:This innovative and intensive home-based exercise intervention was feasible in a small subset of patients with stable gliomas who were interested in exercising. The observed effects suggest that the programme may improve cardiorespiratory fitness. These results support the need for large-scale trials of exercise interventions in brain tumour patients.

Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is cognitive rehabilitation. Background: There is a paucity of literature on the rationale, design, and content of successful cognitive rehabilitation programmes. In the current paper, we describe in detail a cognitive rehabilitation programme that has previously proven effective in a randomized controlled trial in patients with primary brain tumours. The programme’s content may be of practical interest to those working with populations of cognitively impaired patients. Programme: The programme consists of six weekly, individual, 2-hour sessions plus homework, and incorporates both strategy training and attention retraining. The elements were taken from two of the few programmes that are evidence-based. It's design consists of psycho-education, teaching of strategies to compensate for problems in attention, memory and executive functioning in daily life. The retraining was based on the assumption that a target process can be improved by frequently practising exercises. It is focused on attention as intact attention may also be necessary for adequate functioning of other cognitive domains. The hierarchically organized exercises, embedded in a game-like computer program, were tailored to the needs of the individual patient. Evaluation: Mean total training time was estimated to be 35 hours in seven weeks. Adherence to the programme was high. The majority of the participants found the programme to be (very) useful. However, older participants found the programme more burdensome than younger patients. Discussion: Splitting up and spreading out sessions may increase the feasibility and usefulness of the programme for older participants. Further suggestions for improvements and future studies on this programme are also provided.

BACKGROUND: Cognitive dysfunction in patients with non-functioning pituitary adenoma (NFPA) primarily pertains to memory and executive functioning. Current literature is comprised of studies employing dissimilar methodological approaches and there is little prospective research using standardized cognitive function measures before and after surgical tumor resection. This study investigated group and individual cognitive status and change over time. MATERIAL AND METHODS: Forty-five patients underwent neuropsychological assessment one day before and 3 months after transsphenoidal surgery. A computerized neuropsychological test-battery (CNSVS) was used to measure cognitive functioning on 7 domains: Verbal Memory, Visual Memory, Processing Speed, Psychomotor Speed, Reaction Time, Complex Attention and Cognitive Flexibility. Analyses of cognitive status and change were conducted on group and individual level. Associations of preoperative performance with tumor expansion, categorized according to Wilson-Hardy and Knosp classifications, and hormonal deficiency were investigated in exploratory analyses. RESULTS: As a group, patients scored significantly lower than healthy controls on all domains except Visual memory before as well as three months after surgery. Fifty-six percent of patients showed impairment (z-score ≤ - 1.5) on at least one domain before surgery and 63% after surgery. Patients showed no significant change over time as a group, but we found almost equal proportions of patients showing reliable improvement, decline, and stable performance. Degree of suprasellar extension and cavernous sinus invasion did not show a significant relationship with pre-operative cognitive status. Hormonal deficiency was related to Verbal Memory performance. CONCLUSION: Over half of patients showed cognitive impairment before as well as after surgery and dysfunction involved processing and psychomotor speed domains in addition to memory and executive functioning. Differential patterns of reliable cognitive change over time in individual patients were masked in group-level analyses. Future studies with larger samples sizes should address predictors of peri-operative cognitive status and the varied post-surgical course.

BACKGROUND: Monitoring of symptoms and quality of life in patients with primary brain tumors is increasingly being supported with information of informal caregivers, but research on patient-proxy agreement is limited. In this study, the level of agreement between patient-report and patient-by proxy-report of executive functioning was evaluated. MATERIAL AND METHODS: Data of this study were collected in a larger ongoing prospective study on cognitive rehabilitation in brain tumor patients in the Elisabeth-TweeSteden Hospital Tilburg, The Netherlands (ClinicalTrials.gov NTC03373487). Three months after surgery, patients and their informal caregivers completed the adult version of the Behaviour Rating Inventory of Executive Function (BRIEF-A). This 75-item questionnaire addresses different aspects of executive function. The index-scores, i.e. Behavioral Regulation and Metacognition, and the total scores of patients and proxies were evaluated. Mean scores of patients and proxies were compared using two-tailed paired-sample t-tests. Concordance correlation coefficients (CCCs) were calculated and Bland-Altman plots were evaluated. RESULTS: A total of 43 dyads were included in the study. Patients (51% female) had a mean age of 51.1 (±11.0) years. Twenty-five patients underwent resective surgery for a meningioma and 18 for a low-grade glioma. Mean scores of patients and proxies did not differ significantly (p-values > .05). CCCs of .63, .58 and .63 were found for Behavioral Regulation, Metacognition and the total score respectively, indicating moderate to substantial concordance. Bland-Altman plots demonstrated agreement between patient and proxy ratings, with over 95% of the data points lying between the limits of agreement (Mean(diff) ± 2SD(diff)), for the index and total scores. CONCLUSION: Preliminary findings suggest that there is congruence between patients and proxies in the evaluation of patients’ executive functioning after brain tumor surgery. Final results from approximately 50 dyads will be presented at the conference. Also, the relation with objective measures of executive functioning will be presented, as well as the potential influence of tumor location and tumor type. This research was supported by the Dutch organization for health research and innovation (ZonMw, project number 842003009).

Patients with brain tumors may suffer from cognitive deficits caused by the disease and/or its treatment. Here, we review recent efforts in the research on prevention or treatment of cognitive deficits in these patients. We conclude that interest in this area is growing, but that methodological difficulties persist. In addition, we describe the recently completed first randomized controlled trial on the effectiveness of cognitive rehabilitation that we conducted in patients with brain cancer. By reflecting on the methodological challenges experienced in our trial, we hope to assist others in planning and conducting future studies on both pharmacological treatments and cognitive rehabilitation programs for cognitive deficits in this patient population. We conclude with suggestions for future research directions.

This systematic review evaluates relevant findings and methodologic aspects of studies on cognitive functioning in meningioma patients prior to and/or following surgery with or without adjuvant radiotherapy. PubMed and Web of Science electronic databases were searched until December 2015. From 1012 initially identified articles, 11 met the inclusion criteria for this review. Multiple methodological limitations were identified which include the lack of pre-treatment assessments, variations in the number and types of neuropsychological tests used, the normative data used to identify patients with cognitive deficits, and the variety of definitions for cognitive impairment. Study results suggest that most of meningioma patients are faced with cognitive deficits in several cognitive domains prior to surgery. Following surgery, most of these patients seem to improve in cognitive functioning. However, they still have impairments in a wide range of cognitive functions compared to healthy controls. Suggestions are given for future research. Adequate diagnosis and treatment of cognitive deficits may ultimately lead to improved outcome and quality of life in meningioma patients.

Background Studies in cancer and noncancer populations demonstrate lower than expected correlations between subjective cognitive symptoms and cognitive functioning as determined by standardized neuropsychological tests. This paper systematically examines the association between subjective and objective cognitive functioning in patients with low-grade glioma and the associations of these indicators of cognitive function with clusters of sociodemographic, clinical, and self-reported physical and mental health factors. Methods Multiple regression analyses with the subjective and 2 objective indicators of cognitive functioning as dependent variables and 4 clusters of predictor variables were conducted in 169 patients with predominantly low-grade glioma. Results Correlations between the subjective and the 2 objective cognitive indicators were negligible (0.04) to low (0.24). Objective cognitive deficits were predominantly associated with sociodemographic (older age, lower education, male sex) and clinical (left hemisphere tumor) variables, while lower ratings of subjective cognitive function were more closely related to self-reported mental health symptoms (fatigue, lower mental well-being), physical (motor) dysfunction and female sex. Self-reported communication deficits were associated significantly with both subjective and objective dysfunction. Conclusions We recommend that both subjective and objective measures of cognitive functioning, together with a measure of psychological distress, be used for comprehensive neuropsychological assessments of patients with glioma to determine which areas are most affected and which specific intervention strategies are most appropriate.

Introduction: Fatigue is a common symptom in patients with primary brain tumors and may have major impact on quality of life. However, little research has been done on fatigue in patients with a meningioma. The primary aim of this study was to examine the prevalence and severity of fatigue among patients with a meningioma one year after neurosurgery. Materials and Methods: This study is part of a larger ongoing study in brain tumor patients in the Elisabeth-TweeSteden Hospital Tilburg, The Netherlands. One year after surgery, patients with a meningioma (WHO grade I) completed the Multidimensional Fatigue Inventory (MFI). This 20-item self-report instrument covers five dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Patients’ scores were compared to representative normative data. Z-scores, corrected for age and sex, were calculated for each dimension. One-sample t-tests (test-value = 0) were conducted on the mean Z-scores, to evaluate patients’ level of fatigue at group level. By using cut-offs of Z-score > 1.65 and Z-score > 1.96, percentages of patients with (very) high fatigue scores were determined. Results: Twenty-eight meningioma patients (86% female), with a mean age of 55.8 (SD = 11.4) years, were included in the study. On average, patients scored significantly higher on all dimensions of the MFI (all p-values < .02). The largest mean differences in Z-scores were found on General Fatigue (Mdiff = 1.07) and Mental Fatigue (Mdiff = 1.03). Of 28 patients, 15 (54%) reported clinically relevant fatigue (Z-score > 1.65 on one or more dimensions of fatigue). Of these 15 patients, 13 scored even very high (Z-score > 1.96) on one or more dimensions of fatigue. Final results from a larger sample will be presented at the conference. Conclusion: This study systematically examines the prevalence and severity of fatigue in meningioma patients using a multidimensional instrument. Preliminary results demonstrate that, one year after surgery, clinically relevant fatigue is highly present in patients with a meningioma. This emphasizes the need for follow-up assessment and appropriate treatment for these patients.

Background Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non‐pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014. Objectives To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation. Search methods For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022. Selection criteria We included randomised controlled (RCTs) trials that evaluated pharmacological or non‐pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure. Data collection and analysis Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled. Main results Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated “prevention” of cognitive problems (during radiotherapy and follow‐up) and four studies investigated “amelioration” (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non‐pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta‐analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the “early radiotherapy treatment phase” were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d‐threo‐methylphenidate hydrochloride). Non‐pharmacological studies in the “early radiotherapy treatment phase” included a ketogenic diet and a two‐week cognitive rehabilitation and problem‐solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d‐threo‐methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie‐restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The “amelioration” pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non‐pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had “stable” brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias. Authors' conclusions In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non‐pharmacological interventions in the amelioration of cognitive deficits. Further research is required.