Karin Gehring

Interventions for cognitive deficits in adults with brain tumours

Increased life expectancy in patients with brain tumours has led to a greater risk of cognitive deficits, particularly during disease-free periods. Here, we review the empirical studies that have been done to treat or to prevent cognitive impairment in patients with brain tumours. Both pharmacological interventions and cognitive rehabilitation programmes have been used. Although both types of study have reported some successes, these are often difficult to interpret owing to limitations in the methods used. Most of the studies reviewed did not use a randomised group design to control for possible confounding factors such as placebo and practice effects. Investigations of newer, targeted therapies have reported delays in cognitive deterioration, but these need to be confirmed in future studies. Neuroprotection represents another potentially promising, novel approach to prevention of cognitive impairment in this vulnerable population of patients. Finally, we describe studies in patients with cancers outside the CNS, to highlight further possibilities for the prevention and treatment of cognitive deficits.

Review of recent studies on interventions for cognitive deficits in patients with cancer

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.

Interventions for cognitive deficits in patients with a brain tumor: an update

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.

A description of a cognitive rehabilitation programme evaluated in brain tumour patients with mild to moderate cognitive deficits

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. Its 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.

Cognitive functioning in meningioma patients: a systematic review.

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.

Indicators for cognitive performance and subjective cognitive complaints in multiple sclerosis: a role for advanced MRI?:

Previous studies showed that advanced neuroimaging measures (functional MRI, diffusion tensor imaging) could distinguish multiple sclerosis (MS) patients with and without cognitive impairment. Are these measures indeed better indicators for cognitive impairment or subjective cognitive complaints than conventional MRI? Fifty MS patients and 29 controls were investigated. Regression analysis, including socio-demographic data, disease characteristics, psychological measures, and (advanced) neuroimaging, showed that worse cognitive performance was associated with male sex, lower education, and lower gray matter volume. Subjective cognitive complaints were associated with fatigue and less hippocampal atrophy. Advanced MRI measures did not add to the predictive power of our model.

Evaluation of Normative Data of a Widely Used Computerized Neuropsychological Battery: Applicability and Effects of Sociodemographic Variables in a Dutch Sample:

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.

Test-retest reliability and practice effects of a computerized neuropsychological battery : A solution-oriented approach

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.

Feasibility of a home-based exercise intervention with remote guidance for patients with stable grade II and III gliomas : A pilot randomized controlled trial

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.

Group changes in cognitive performance after surgery mask changes in individual patients with glioblastoma

BACKGROUND There is a growing interest to include evaluations of cognitive performance in the clinical management of patients with glioblastoma (GBM). However, as changes in cognitive performance of a group may mask changes in individual patients, study results are often difficult to transfer into clinical practice. We focused on the comparison of group versus individual changes in neuropsychological performance of patients with GBM after initial surgical treatment. METHODS Patients underwent neuropsychological evaluation using CNS Vital Signs 1 day prior to and 3 months after surgery. Two-tailed paired-samples t tests were conducted to assess changes on the group level. Reliable change indices (RCIs) that correct for practice effects and imperfect test-retest reliabilities were used to examine changes in individual patients. RESULTS Cognitive dysfunction was common (>80%) both before and 3 months after surgery in this sample of 82 patients with GBM. Whereas group analyses revealed minimal changes in performance over time, RCIs demonstrated that most patients (89%) showed changes in performance in at least 1 cognitive domain. Half of these individual patients solely showed improvements, a quarter solely showed declines, and another quarter showed both improvements and declines. CONCLUSIONS This study clearly demonstrates that important individual changes in performance are masked when looking only at group results. Future studies should more often use an individual patient approach to enhance knowledge transfer into clinical practice.