Cognitive complaints in patients with untreated obstructive sleep apnea versus patients with neurological and respiratory diseases: prevalence, severity and risk factors.

PURPOSE: Little is known about cognitive complaints (self-reported problems in cognitive functioning) in patients with Obstructive Sleep Apnea (OSA). We compared the prevalence and severity of cognitive complaints in patients with untreated OSA to patients with neurological and respiratory diseases. We also studied risk factors for cognitive complaints across these diseases, including OSA. METHODS: We used a convenience sample to compare untreated OSA patients (N = 86) to patients with stroke (N = 166), primary brain tumor (N = 197) and chronic obstructive pulmonary disease (COPD, N = 204) on cognitive complaints (Cognitive Failure Questionnaire, CFQ), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and cognitive impairments using neuropsychological tests. We combined all patient groups (OSA, stroke, brain tumor and COPD) and studied potential risk factors (demographic variables, anxiety, depression and cognitive impairments) for cognitive complaints across all patient groups using regression analysis. RESULTS: The prevalence of cognitive complaints was higher in OSA patients and complaints of forgetfulness and distractibility were more severe compared to stroke and primary brain tumor patients, but similar to or lower than COPD patients. Regression analysis for the combined sample of all patient groups showed that cognitive complaints were most strongly associated with symptoms of anxiety and depression. CONCLUSION: A high rate of OSA reported clinically significant cognitive complaints, comparable to other respiratory and neurological patients. Symptoms of anxiety and depression are important risk factors for cognitive complaints in patients with various neurological and respiratory diseases. Future studies should examine the relation between anxiety, depression and cognitive complaints in patients with OSA.

Factors associated with the local control of brain metastases: a systematic search and machine learning application.

BACKGROUND: Enhancing Local Control (LC) of brain metastases is pivotal for improving overall survival, which makes the prediction of local treatment failure a crucial aspect of treatment planning. Understanding the factors that influence LC of brain metastases is imperative for optimizing treatment strategies and subsequently extending overall survival. Machine learning algorithms may help to identify factors that predict outcomes. METHODS: This paper systematically reviews these factors associated with LC to select candidate predictor features for a practical application of predictive modeling. A systematic literature search was conducted to identify studies in which the LC of brain metastases is assessed for adult patients. EMBASE, PubMed, Web-of-Science, and the Cochrane Database were searched up to December 24, 2020. All studies investigating the LC of brain metastases as one of the endpoints were included, regardless of primary tumor type or treatment type. We first grouped studies based on primary tumor types resulting in lung, breast, and melanoma groups. Studies that did not focus on a specific primary cancer type were grouped based on treatment types resulting in surgery, SRT, and whole-brain radiotherapy groups. For each group, significant factors associated with LC were identified and discussed. As a second project, we assessed the practical importance of selected features in predicting LC after Stereotactic Radiotherapy (SRT) with a Random Forest machine learning model. Accuracy and Area Under the Curve (AUC) of the Random Forest model, trained with the list of factors that were found to be associated with LC for the SRT treatment group, were reported. RESULTS: The systematic literature search identified 6270 unique records. After screening titles and abstracts, 410 full texts were considered, and ultimately 159 studies were included for review. Most of the studies focused on the LC of the brain metastases for a specific primary tumor type or after a specific treatment type. Higher SRT radiation dose was found to be associated with better LC in lung cancer, breast cancer, and melanoma groups. Also, a higher dose was associated with better LC in the SRT group, while higher tumor volume was associated with worse LC in this group. The Random Forest model predicted the LC of brain metastases with an accuracy of 80% and an AUC of 0.84. CONCLUSION: This paper thoroughly examines factors associated with LC in brain metastases and highlights the translational value of our findings for selecting variables to predict LC in a sample of patients who underwent SRT. The prediction model holds great promise for clinicians, offering a valuable tool to predict personalized treatment outcomes and foresee the impact of changes in treatment characteristics such as radiation dose.

A randomized trial predicting response to cognitive rehabilitation in multiple sclerosis: Is there a window of opportunity?

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.

Neurocognition in adults with intracranial tumors: does location really matter?

OBJECTIVE: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. METHODS: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p < .001 and p < .05 for voxel- and cluster-level, resp.). RESULTS: A cohort of 179 intracranial tumor patients was included [aged 19-85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20-30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. INTERPRETATION: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved.

A systematic review of the use of subcortical intraoperative electrical stimulation mapping for monitoring of executive deficits and neglect: what is the evidence so far?

BACKGROUND: Over the past decade, the functional importance of white matter pathways has been increasingly acknowledged in neurosurgical planning. A method to directly study anatomo-functional correlations is direct electrical stimulation (DES). DES has been widely accepted by neurosurgeons as a reliable tool to minimize the occurrence of permanent postoperative motor, vision, and language deficits. In recent years, DES has also been used for stimulation mapping of other cognitive functions, such as executive functions and visuospatial awareness. METHODS: The aim of this review is to summarize the evidence so far from DES studies on subcortical pathways that are involved in visuospatial awareness and in the following three executive functions: (1) inhibitory control, (2) working memory, and (3) cognitive flexibility. RESULTS: Eleven articles reported on intraoperative electrical stimulation of white matter pathways to map the cognitive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the right SLF-II is involved in visuospatial awareness, the left SLF-III and possibly the right SLF-I are involved in working memory, and the cingulum is involved in cognitive flexibility. CONCLUSIONS: We were unable to draw any more specific conclusions, nor unequivocally establish the critical involvement of pathways in executive functions or visuospatial awareness due to the heterogeneity of the study types and methods, and the limited number of studies that assessed these relationships. Possible approaches for future research to obtain converging and more definite evidence for the involvement of pathways in specific cognitive functions are discussed.

eHealth cognitive rehabilitation for brain tumor patients: results of a randomized controlled trial.

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.

The APOE ε4 allele in relation to pre- and postsurgical cognitive functioning of patients with primary brain tumors.

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.

Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients.

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.

Assessment of Executive Functioning in Patients with Meningioma and Low-Grade Glioma: A Comparison of Self-Report, Proxy-Report, and Test Performance.

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.

Health-related quality of life in adult patients with brain metastases after stereotactic radiosurgery: a systematic, narrative review.

PURPOSE: A 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. METHODS: We 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. RESULTS: Out 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. CONCLUSIONS: In 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.

Predicting self-esteem in informal caregivers of people with dementia: Modifiable and non-modifiable factors.

While informal caregivers often feel burdened by the care for a person with dementia, they can also experience positive consequences due to caregiving; caregiver gains. One of these, relatively overlooked, caregiver gains is heightened self-esteem. We assessed the predictive ability of non-modifiable (caregiver sociodemographic- and dementia related-) and modifiable (psychological-) factors for caregiver self-esteem). A cross-sectional study in which 201 caregivers, who spent at least eight hours a week on caring for a community-residing person with dementia, completed a semi-structured interview and five questionnaires. One two-block (1: non-modifiable-; 2: modifiable variables) hierarchic multiple regression analysis was used to assess which variables predicted self-esteem. None of the non-modifiable variables significantly predicted self-esteem. Regarding the modifiable variables, depression and relationship quality with the person with dementia significantly predicted self-esteem (adjusted R2 = .460, ß = -.207, p = .015 and ß = .632, p < .001 respectively). Caregivers who experience a better relationship quality with the person with dementia, and fewer depression symptoms, experience a higher level of self-esteem. Interventions focused on heightening self-esteem should strive to optimize these factors to enhance the lives of informal dementia caregivers.

Episodic memory and executive functioning in informal dementia caregivers.

Objectives: Informal dementia caregivers are thought to experience high levels of depression and burden, which can contribute to worse cognitive functioning. However, poorer cognitive functioning in caregivers is not always found. The current study explored whether caregivers perform better, worse, or similar to non-caregivers on tasks for executive functioning and memory. Whether sociodemographic and psychosocial characteristics are associated with caregivers' performance was also assessed.Methods: One hundred forty-five caregivers completed the Letter Fluency and Category Fluency, the Logical Memory test from the WMS-III, and five questionnaires assessing psychological characteristics. Standardized z-scores (based on age, education, and sex) were calculated using data from a matched control group (187 non-caregivers). One sample z-tests were executed to examine if the caregivers' standardized mean z-score significantly deviated from the population mean of z = 0. The z-scores were used as dependent variables in multivariable regression analyses.Results: The caregivers performed significantly better on Logical Memory - Immediate Recall than non-caregivers (z = 2.92, p = .004). The obtained z-scores on the other tasks did not deviate significantly from 0. Male sex and social reliance predicted higher scores on Category Fluency, but the F-test was non-significant, and the explained variance was low (adjusted R2 = .068).Conclusions: We found no evidence for poorer cognitive performance among informal caregivers compared to non-caregivers. Our results suggest that caregiving for a loved one with dementia does not impair the caregivers' episodic memory or executive functioning when measured cross-sectionally.

Motor Impairment Three Months Post Stroke Implies A Corresponding Cognitive Deficit.

BACKGROUND: While both motor and cognitive impairment are common after stroke, the focus of (early) treatment has always been on motor deficit. AIMS: The objective of the current study was to explore the link between motor and cognitive performance in stroke patients and to examine whether motor performance is associated with cognitive functioning at three months post stroke. METHODS: In both stroke patients (n = 142) and controls (n = 135), with the groups matched on age, gender and premorbid IQ, motor functioning was evaluated using both objective (Purdue Pegboard Test) and subjective measures (specific items from the Frenchay Activities Index and Barthel Index). Cognition, specifically information processing speed, working memory and cognitive flexibility, was assessed using objective tasks. The data were analyzed using Pearson product-moment correlation coefficients and logistic regression. RESULTS: Significant correlations between motor and cognitive functioning were found in stroke patients. The objective motor task was stronger than subjective measures in statistically explaining and predicting cognitive deficit, irrespective of stroke severity. CONCLUSIONS: We conclude that motor impairment at three months post-stroke should serve as a 'red flag' for professionals: cognitive impairment is likely and should also be evaluated.

Course and Predictors of Subjective Cognitive Complaints During the First 12 Months after Stroke.

BACKGROUND: Subjective Cognitive Complaints (SCC) are common after stroke. This study documents the prevalence and course of SCC in the first year after stroke and determines which patient characteristics in the first 3 months predict subsequent SCC at 1-year follow-up. METHODS: Using a longitudinal design, 155 patients (mean age 64.0 ± 11.9 years; 69.7% men) were assessed at 3 and 12 months after stroke. SCC were assessed using the Checklist for Cognitive and Emotional consequences following stroke (CLCE) inventory (content component [CLCE-c] and worry component [CLCE-w]). Potential predictors of 12 months SCC included demographics, stroke severity, objective cognitive impairment, psychological factors (depression, anxiety, perceived stress, fatigue, personality traits, coping style), and activities of daily life functioning assessed at 3 months poststroke. Multiple hierarchical linear regression analyses were used to determine predictors of SCC at 12 months poststroke. RESULTS: SCC remained stable from 3 to 12 months over time (CLCE-c from 3.3 ± 2.4 to 3.3 ± 2.6; CLCE-w: from 1.9 ± 2.2 to 2.1 2.5). Independent predictors of SCC at 12 months were baseline CLCE-c (ß = 0.54) and perceived stress (ß = 0.23) for content, and baseline CLCE-w (ß = 0.57) and depressive symptoms (ß = 0.23) for worry. CONCLUSIONS: Patients who report SCC at 3 months after stroke are likely to continue having these complaints at 1 year follow-up. Perceived stress and depressive symptoms additionally increase the likelihood of having SCC at 12 months, independent of SCC at 3 months poststroke. Rehabilitation programs that target reduction of stress and depression in the first months after stroke might reduce sustained SCC and improve well-being.

Cognitive functioning in glioma patients is related to functional connectivity measures of the non-tumoural hemisphere.

Previous studies have shown that cognitive functioning in patients with brain tumour is associated with the functional network characteristics of specific resting-state networks or with whole-brain network characteristics. These studies, however, did not acknowledge the functional contribution of areas in the contralesional, non-tumoural hemisphere, even though these healthy remote areas likely play a critical role in compensating for the loss of function in damaged tissue. In the current study, we examined whether there is an association between cognitive performance and functional network features of the contralesional hemisphere of patients with glioma. We found that local efficiency of the contralesional hemisphere was associated with performance on the reaction time domain, whereas contralesional assortativity was associated with complex attention and cognitive flexibility scores. Our results suggest that a less segregated organization of the contralesional hemisphere is associated with better reaction time scores, whereas a better spread of information over the contralesional hemisphere through mutually interconnected contralesional hubs is associated with better cognitive flexibility and better complex attention scores. These findings urge researchers to recognize the functional contribution of remote, undamaged regions and to focus more on the graph metrics of the contralesional hemisphere in the search for predictors of cognitive functioning in patients with brain tumour.

Health-related quality of life of patients with brain metastases selected for stereotactic radiosurgery.

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.

Cognitive functioning and predictors thereof in patients with 1-10 brain metastases selected for stereotactic radiosurgery.

PURPOSE: Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery. METHODS: Cognition was measured before radiosurgery using a standardized neuropsychological test battery in patients with 1-10 BM (expected survival > 3 months; KPS ≥ 70; no prior BM treatment). Regression formulae were constructed to calculate sociodemographically corrected z scores. Group and individual cognitive functioning was analyzed. Multivariable regression was used to explore potential predictors. RESULTS: Patients (N = 92) performed significantly worse than controls (N = 104) on all 11 test variables (medium-large effect sizes for 8 variables). Percentages of impairment were highest for information processing (55.3%), dexterity (43.2%) and cognitive flexibility (28.7%). 62% and 46% of patients had impairments in at least two, or three test variables, respectively. Models including combinations of clinical and psychological variables were predictive of verbal memory, psychomotor speed, information processing and dexterity. Neither number nor volume of metastases predicted patients' test performance. CONCLUSIONS: Already before radiosurgery, almost half of the patients suffered from severe cognitive deficits in at least three test variables. At group and individual level, information processing, cognitive flexibility, and dexterity were most affected. These cognitive impairments may impair daily functioning and patients' ability to make (shared) treatment decisions. Both clinical (symptomatic BM; timing of BM diagnosis) and psychological (mental fatigue) characteristics influenced cognitive performance. CLINICAL TRIAL INFORMATION: Cognition and Radiation Study A (CAR-Study A; ClinicalTrials.gov Identifier: NCT02953756; Medical Ethics Committee file number: NL53472.028.15/P1515).

Multidimensional assessment of fatigue in patients with brain metastases before and after Gamma Knife radiosurgery.

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 < .001), and levels of mental fatigue decreased significantly (p = .027). No significant predictors of the course of fatigue over time could be identified. CONCLUSIONS: Fatigue is a major problem for patients with BM. Different patterns over time were observed for the various aspects of fatigue in patients with BM. Information on the various aspects of fatigue is important because fatigue may negatively affect patients' functional independence, health-related quality of life, and adherence to therapy.

Predicting disease progression in high-grade glioma with neuropsychological parameters: the value of personalized longitudinal assessment.

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.

Subjective cognitive functioning in patients with a meningioma: Its course and association with objective cognitive functioning and psychological symptoms.

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 postsurgery and its associations with OCF, psychological, sociodemographic, and clinical characteristics. METHODS: SCF was measured using the Cognitive Failures Questionnaire (CFQ) 1 day before (T0) and 3 (T3) and 12 months (T12) after surgery. Patients' scores were compared with 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, P < .001). SCF was associated with anxiety at all time points (rs = -0.543 to -0.352) and with depression at T3 and T12 (r = -0.338 and -0.574), but not with OCF, sociodemographic, or clinical characteristics (rs = -0.202 to 0.288). CONCLUSIONS: Meningioma patients experienced better SCF as compared with controls before and 3 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.