Gehring, K., Sitskoorn, M.M., Gundy, C.M., Sikkes, S.A.M., Klein, M., Postma, T. J., . . . Aaronson, N.K. (2009). Cognitive rehabilitation in patients with gliomas: A randomized, controlled trial. Journal of Clinical Oncology, 27, 3712–3722.

The study was conducted to evaluate the effectiveness of a multifaceted cognitive rehabilitation program's (CRP's) measures of cognitive functioning in patients with gliomas whose disease was in remission.

An eligibility screening was conducted through

1. Telephone interviews confirming at least one cognitive symptom from the Medical Outcomes Study Cognitive Functioning Scale among individuals who expressed an interest in CRP participation.
2. Objective neuropsychological assessment, in which participants performed at least one standard deviation below a healthy comparison group's mean (n = 294) on at least 4 of 20 neuropsychological assessment variables.

The randomization procedure was a minimization method balancing age, sex, education, tumor grade, hemisphere, radiotherapy, neurosurgery, disease duration, and institution.

The control group received standard care without cognitive intervention, and had contact with research staff at similar intervals as the intervention group. Control participants received a telephone-based empathy session during which attention to possible cognitive problems occurred without the provision of advice. At the study's completion, control participants were offered the opportunity to receive the intervention.

The intervention group received six weekly individual sessions of two hours each, carried out by seven neuropsychologists. Two techniques were incorporated. 

1. Cognitive retraining using a computer program (C-Car) consisting of a series of hierarchically graded tasks designed to strengthen various aspects of attention on the basis of patients needs.
2. Compensatory training consisting of six psychoeducational sessions on attention, memory, and executive function. This training included didactic and practical elements aimed to help patients compensate for impaired cognitive function.

• All participants had glioma in remission.
• The total number of participants was 140, with 70 patients each in the treatment group and control group.
• The average participant age was 42 ± 9.4 years for the treatment group.
• The average participant age was 43.8 ± 10.5 years for the control group.
• The treatment group was 58.6% male and 41.4% female.
• The control group was 57.1% male and 42.9% female.
• The median number of years since treatment was 2.6 years for the treatment group.
• The median number of years since treatment was 3.1 years for the control group. 

Patients were recruited from 11 Dutch hospitals, including 10 neurosurgical centers.

The study utilized a randomized, controlled trial.

• Dutch Adult Reading Test (DART) and the Drie-Minuten-Toets Three Minute Test (DMT) for premorbid intelligence
• Stroop Color-Word Test (SCWT), Digit Span (Forward and Backward), Memory Scanning Test (MST), and the Test of Everyday Attention (TEA) for attention
• Multidimensional Fatigue Inventory (MFI) for mental fatigue, activity, and motivation
• Community Intervention Questionnaire (CIQ) for home integration, social integration, and productivity
• Visual Verbal Learning Test (VVLT) for memory
• Concept Shifting Test (CST), Letter Fluency (LF), and Category Fluency (CF) for executive function
• Medical Outcomes Study Cognitive Functioning Scale
• Cognitive Failure Questionnaire (CFQ)
• Behavioral Assessment of Dysexecutive Syndrome (BADS)

Eighty percent of CRP subjects reported that the intervention addressed their problems; 87% used compensation strategies regularly, and 79% indicated a decrease in the impact of cognitive problems on daily functioning. The intervention group had significantly better combined attention scores (in four out of seven tests) than the control group (p = 0.004) at the six-month follow-up. Verbal memory and attention were improved for the intervention group at the six-month follow-up, suggesting the intervention's success with some sustainment in learned skills.

Effect sizes for the CRP ranged from 0.23 to 0.55. The intervention group had significantly better combined scores on verbal memory tests than the control group (p = 0.009). Effect sizes for the intervention group on two of three tests were 0.48 and 0.43. Mental fatigue on the MFI was improved in the intervention group at the six-month follow-up (p = 0.044), with an effect size of 0.41.

Self-reported cognitive function (CFS, CFQ, burden) was better in the intervention group on completion of the CRP (p = 0.001). Effect sizes ranged from 0.31 to 0.48. However, at the six-month follow-up this improvement was maintained, while the control group continued to improve.

There were no significant differences between groups on neuropsychiatric assessment scores at baseline. There were no statistically significant group differences in attention or verbal memory scores at completion of the CRP.

CRP was useful in improving cognitive function, with sustained improvements in verbal memory and attention over time.

• Mild cognitive impairment was detected by baseline cognitive function scores in the majority of subjects, which could impact the expected change from the CRP intervention (ceiling effect).
• The study did not indicate whether hemispheric location of the tumor influenced cognitive functioning.
• The authors did not specify whether they controlled for tumor characteristics, seizure frequency, and use of anti-epileptics in the analyses.