Cognitive Training

• FINAL NUMBER STUDIES INCLUDED = 13
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,138
• SAMPLE RANGE ACROSS STUDIES = 20–210 patients
• KEY SAMPLE CHARACTERISTICS: Most studies included only women with breast cancer. All participants received chemotherapy with or without radiation therapy or hormonal therapy. Most participants were aged about 55 years. The majority of studies were conducted in the United States. Most outcomes were evaluated in the short-term (i.e., less than three months).

PHASE OF CARE: Late effects and survivorship

Risk of bias was high in 11 studies but unclear in  two studies that evaluated psychostimulants.

Pharmacologic interventions: No improvements in cognitive function were found using psychostimulants (four studies) or ginkgo biloba. Patients reported better cognitive function using epoetin alfa with doses titrated for hemoglobin levels (p < 0.05). However, a death caused by a cerebrovascular accident was noted.

Nonpharmacologic interventions: Small-group memory training improved self-reported cognitive function, and both memory and speed of processing after small-group training improved immediate and delayed recall (p < 0.05). Home-based online executive function training improved verbal function and attention (p < 0.05). Speed-feedback therapy during biking improved executive and motor function (p < 0.05). Cognitive behavioral therapy-based interventions (two studies), Tibetan sound meditation, and hatha yoga did not improve cognitive function.

The pharmacologic studies reviewed did not support the use of psychostimulants or ginkgo biloba to improve cognitive function after chemotherapy for breast cancer. Epoetin alfa was not recommended for practice because of safety concerns. The nonpharmacologic studies reviewed provided some evidence that cognitive training and speed-feedback therapy might improve cognitive function for breast cancer survivors.

The risk of bias was high for most studies. Therefore, although positive results were found, well-designed, prospective RCTs need to be completed to confirm these findings. It is unclear how sustainable the positive results of the cognitive training and exercise interventions might be because follow-up was limited to less than three months.

This systematic review provided limited support for cognitive training and structured exercise to improve cognitive function after chemotherapy for breast cancer. Cognitive training is currently categorized as likely to be effective for cognitive impairment.

• FINAL NUMBER STUDIES INCLUDED = 12
• TOTAL PATIENTS INCLUDED IN REVIEW = 442
• SAMPLE RANGE ACROSS STUDIES = 12–107 patients
• KEY SAMPLE CHARACTERISTICS: Although education status may influence neuropsychological test results, only half of the studies provided this information. Likewise, menopausal status may affect cognition, and this was only reported by two thirds of the studies.

PHASE OF CARE: Late effects and survivorship

Studies of pharmacologic interventions were not found to be effective in improving cognitive function. Medications reviewed included d-methylphenidate (n = 1), epoetin alfa (n = 2), and ginkgo biloba (n = 1). Evidence for nonpharmacologic interventions was mixed. No improvements in cognitive function were found with Tibetan sound meditation (n = 1). Natural restorative therapy (n = 1) improved attention only when comparing the baseline with the final 90-day evaluation (p = 0.01). Exercise (n = 1) improved attention (p = 0.019) and verbal memory (p = 0.048) but not working memory. Cognitive rehabilitation (n = 1) improved four out of six measures of information processing speed (p < 0.05) but not attention, verbal memory, or executive function. Cognitive behavioral training (n = 2) improved verbal memory (p < 0.05) in both studies and was effective in improving in information processing speed when compared to baseline scores in one study (p ≤ 0.01) but not the other. Computerized cognitive training was effective in one study in improving processing speed (p = 0.009), executive function (p = 0.008), and a measure of executive function and language (p = 0.003) but not verbal memory. However, in another study, there was no difference in verbal memory or information processing speed between the intervention and control groups.

Nonpharmacologic interventions, especially cognitive training, may have a role for improving attention, information processing speed, and verbal memory. Exercise and computerized cognitive training may be effective for improving executive function. However, additional research validating these findings with larger sample sizes and evaluating other cognitive domains is needed. In addition, studies determining the dose or duration of interventions is required for a durable response.

• A small number of studies (n = 12) were included in the review for multiple types of interventions.
• Only one study had a sample size greater than 100 (range = 12–107).
• Studies of low quality were included. 

These findings suggest that nonpharmacologic, not pharmacologic, interventions may be helpful in managing chemotherapy-induced cognitive impairment in patients with breast cancer. However, these findings were based on a small number of studies per intervention. Additional research validating which interventions might be useful in improving cognitive impairments in women receiving chemotherapy for breast cancer is needed. 

STUDY PURPOSE: To examine nonpharmacologic intervention effects on cognitive function in adult survivors of cancer, and to examine whether these effects are driven by psychological or behavioral intervention types

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 systematic reviews,11 meta-analyses
• TOTAL PATIENTS INCLUDED IN REVIEW = 977
• SAMPLE RANGE ACROSS STUDIES: 13–157 patients 
• KEY SAMPLE CHARACTERISTICS: The mean age was 53.1 years. Cancer diagnoses were breast (n = 7), glioma (n = 3), mixed diagnoses (n = 3), and hematologic (n = 1). Stage not mentioned (n = 4), stage I–III (n = 7), all stages (n = 3)

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care

Eleven studies used psychological interventions, and three used behavioral interventions. All studies used standard care control groups, with intervention durations of two weeks to more than one year that included an average of 16 one-hour sessions. Psychological interventions used individual-based cognitive rehabilitation (n = 10) with three using computer-based retraining programs. Outcomes included subjective cognitive function (n = 5), attention (n = 6), memory (n = 8), executive function (n = 7), verbal ability (n = 3),  and multiple domains (n = 7). Low risk bias assessments: Rrandomization (n = 5), allocation concealment (n = 3), blinded participants or personnel (n = 2), blinded personnel conducting outcome assessment (n = 4), attrition (n = 12), reporting bias (n = 14), monitoring procedures, and manual use (n = 13). Statistical heterogeneity ranged from none to moderate (I² = 0%–68%). Significant treatment effects existed for nonpharmacologic interventions on memory (n = 8, d = 0.21, 95% confidence interval [CI] [0.04, 0.38], p = 0.02, I² = 0%) and perceived cognitive function (n = 5, d = 0.41, 95% CI [0.2, 0.61], p < 0.001, I² = 0%). Subgroup analysis for psychological interventions was significant for effect on perceived cognitive function (n = 3, d = 0.35, 95% CI [0.13, 0.58], p = 0.002, I² = 0%).

The treatment effects of nonpharmacologic interventions significantly improved memory and perceived cognitive function. The meta-analysis indicated that psychological interventions significantly improved perceived cognitive function. No treatment effects from other interventions were observed, and no effects on cognitive performance in domains of executive function, attention, and verbal ability were observed. Most studies reviewed in this meta-analysis did not provide sufficient evidence to demonstrate improvement in cognitive performance. Further study is warranted using RCT designs to increase the sample pool to observe positive treatment effects.

• Limited number of studies included
• Low sample sizes

Nonpharmacologic interventions, specifically those involving psychological interventions, have demonstrated improvements in memory and self-reported cognitive function in adult survivors of cancer.

STUDY PURPOSE: To determine the effectiveness of nonpharmacologic interventions for minimizing chemotherapy-induced cognitive impairment in adult patients with breast cancer.

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, Embase, PubMed, CINAHL, PsycINFO, and CENTRAL (Cochrane Centre Register of Controlled Trials) 

YEARS INCLUDED: (Overall for all databases) 1980 through September 29, 2015

INCLUSION CRITERIA: Randomized controlled trials evaluating the effectiveness of nonpharmacologic interventions on maintaining or improving cognitive function in cancer survivors who completed chemotherapy (including those currently on hormonal therapy)  

EXCLUSION CRITERIA: Studies involving participants with primary or metastatic central nervous system (CNS) disease, nonmelanoma skin cancer, and/or patients in nursing home or residential care settings

TOTAL REFERENCES RETRIEVED: 255 screened (plus 47 additional records), but 40 assessed for study eligibility 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane risk of bias tool was utilized to evaluate study quality.

FINAL NUMBER STUDIES INCLUDED: 5

TOTAL PATIENTS INCLUDED IN REVIEW: 235

SAMPLE RANGE ACROSS STUDIES: 100% female; all patients received chemotherapy and/or hormonal therapy 

KEY SAMPLE CHARACTERISTICS: Breast cancer survivors

PHASE OF CARE: Transition phase after active treatment

Five randomized clinical trials compared an intervention with wait-list controls to improve various cognitive functions (i.e., memory, information processing speed [IPS], executive functioning [EF]). Nonpharmacologic interventions included cognitive behavioral therapy (n = 1), cognitive training (n = 2), meditation through Tibetan sound therapy (n = 1), and aerobic exercise (n = 1).

• Cognitive behavioral therapy significantly improved verbal memory (p < 0.05), but not IPS or patients' perceived cognitive functioning.  
• Two trials evaluated cognitive training. The first study compared cognitive training in IPS or memory to controls and found improved immediate and delayed memory (p < 0.01) in the IPS group as well as better immediate (p = 0.036) and delayed memory (p = 0.013) in the memory group. In addition, both intervention groups found improved subjective cognitive functioning (p < 0.05). The second study used computerized cognitive training and found significant improvements in IPS (p = 0.009) as well as some measures of EF (p = 0.008; p = 0.003).  
• Tibetan sound therapy resulted in no differences for either objective or subjective measures of cognitive function.
• Similarly, no differences were observed between intervention and control groups evaluating aerobic exercise.  

Although cognitive training and cognitive behavioral therapy may be beneficial in improving cognitive functioning, there is insufficient evidence for exercise and meditation. The overall quality of the evidence was determined to be low for all studies included.

Findings from this study revealed that there is insufficient good-quality evidence to determine whether cognitive training, cognitive behavioral interventions, exercise, or meditation may improve cognitive functioning in breast cancer survivors who have received chemotherapy with or without hormonal therapy. However, cognitive training and cognitive behavioral interventions were associated with improvements in objective and subjective measures of cognitive function, so further research including multisite studies with large sample sizes and higher-quality evidence may confirm their effectiveness. Further studies are needed to determine whether exercise and/or meditation might have a role in alleviating cognitive impairment.

Limited number of studies included

Mostly low quality/high risk of bias studies

Study findings do not support recommending cognitive training, cognitive behavioral interventions, exercise, or meditation for improving cognitive impairment in breast cancer survivors. However, additional research using these interventions are recommended to further determine their effectiveness.

STUDY PURPOSE: To examine the effects of cognitive training and cognitive rehabilitation interventions on cognitive function in adults with non-central nervous system cancers

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 9 included in the meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 410 included in the meta-analysis
• SAMPLE RANGE ACROSS STUDIES: 22–98 patients 
• KEY SAMPLE CHARACTERISTICS: The mean age in studies ranged from 45–75 years. Cancer diagnoses were breast (n = 4) or mixed non-CNS (n = 5) cancers. Two studies were not randomized. Five studies had sample sizes of less than 40.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care

Three studies tested cognitive training, and six studies tested cognitive rehabilitation. Most studies used waitlist control groups, with intervention durations of one to six months. Outcomes included verbal and/or visual memory (n = 8), executive function (n = 4), attention (n = 6), processing speed (n = 2), language (n = 1), and self-reported cognitive function (n = 9). A moderate-to-high risk of bias was found across studies. Statistical heterogeneity ranged from 0% to 96%. By outcome measure, the number of studies included in each part of the meta-analysis ranged from two to five. Cognitive training and cognitive rehabilitation interventions improved immediate (n = 2, WMD = 7.58, 95% confidence interval [CI] = [0.07, 15.09], p < 0.05) and delayed (n = 2, WMD = 10.85, 95% CI [4.19, 17.51], p = 0.001) memory at post intervention. Both types of interventions improved verbal learning at post intervention (n = 5, SMD = 0.5, 95% CI [0.19, 0.81], p = 0.001) and follow-up (n = 3, SMD = 0.58, 95% CI [0.19, 0.98], p = 0.004). Cognitive training interventions improved self-reported cognitive function at post intervention (n = 2, SMD = 0.52, 95% CI [0.06, 0.98], p = 0.03) and follow-up (n = 2, SMD = 0.54, 95% CI [0.08, 1], p = 0.02).

The meta-analysis indicated that both cognitive training and cognitive rehabilitation interventions may improve objectively measured memory and verbal learning, whereas cognitive training interventions may improve self-reported cognitive function. No treatment effects were found for executive function, attention, processing speed, or language. The weaknesses of this meta-analysis limit its usefulness in determining the effects of these types of interventions on cognitive function.

• Limited number of studies included
• High heterogeneity
• Low sample sizes

Individual-based cognitive training and group-based cognitive rehabilitation may improve objectively measured memory and verbal learning, as well as self-reported cognitive function, in adult survivors of cancer. Because of the small number and weaknesses of included studies, the benefits of these interventions are unclear.

The purpose was to compare results of a cognitive rehabilitation program to standard care in patients reporting cognitive symptoms.

All subjects participated in a 30-minute telephone consultation outlining cognitive compensatory strategies prior to study group assignment. Patients were randomly assigned to intervention and control groups. The intervention was a computerized neurocognitive program targeting visual precision, divided attention, working memory, and visual processing speed, which was provided as a CD. Patients were to use training for four 40-minute sessions per week for 15 weeks. The program had an automated measure of compliance. Study assessments were completed by patients at baseline, after 15 weeks, and 6 months later.

• N = 242 in ITT analysis   
• AGE: Range 23-74 years, median 53
• MALES: 5%  
• FEMALES: 95%
• KEY DISEASE CHARACTERISTICS: Solid tumors; had completed definitive treatment within a mean of 27 months reporting quite a bit of changes or greater in concentration or memory on the EORTC QLC–C30 cognitive function scale. The majority had breast cancer. About 70% were on hormone therapy.

• SITE: Multisite   
• SETTING TYPE: Outpatient    
• LOCATION: Australia

PHASE OF CARE: Late effects and survivorship

Longitudinal randomized clinical trial

• FACT-COG questionnaire
• Cogstate computerized testing
• General Health Questionnaire (for anxiety and depression)
• FACT-General 
• FACT-Fatigue 
• Perceived Stress Scale

Only 86% of those in the intervention group used the program. Average total training time was 25 hours of the recommended 40 hours. Patients in the intervention group had better outcomes on the FACT-Cog compared to controls at 15 weeks on all subscales with better perceived cognitive abilities (p < 0.001), less perceived cognitive impairment (p < 0.001) with less impact on quality of life (p = 0.02), and less comments from others regarding cognitive functioning (p = 0.04). However, these differences were sustained at six months only for perceived cognitive impairment (p = 0.001) and perceived cognitive abilities (p < 0.001) but not for the other subscales. Similarly, those in the intervention group had less anxiety and depression (p = 0.02), fatigue (p = 0.03), and perceived stress (p = 0.03) at 15 months. Differences remained only for perceived stress (p = 0.01) at six months. There were no differences between groups in Cogstate measures of neuropsychological function. There was no evidence of dose response for training time and patient outcomes.

The computerized cognitive rehabilitation program tested here showed benefit in terms of patient-reported outcomes of cognitive function but no effect on objective measures of neuropsychological function. There were short-term improvements in anxiety, depression, and fatigue with the intervention that were not sustained.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Single-scale scores were used for measurement of anxiety and depression outcomes. 14% of the intervention group never used the program, raising the question of overall usefulness for a variety of patients. There were varied numbers of patients lost to follow-up at various time points with different measures and it is not clear which participants and results were included in ITT analysis.

Findings suggest that computerized cognitive rehabilitation may improve patient perceptions of cognitive functioning; however, these findings were not consistent with objective measures. Actual benefit of computerized cognitive training for cancer treatment-related cognitive impairment remains unclear.

To investigate the use of a web-based cognitive training intervention for subjective and objective cognitive complaints in breast cancer survivors

HAPPYneuron Pro^© (Scientific Brain Training, Villeurbanne Cedex, France) is a customized 12-task training program of 6 cognitive domains (attention, processing speed, learning, memory, working memory, problem solving) involving 10 levels of difficulty. The program required a minimum commitment of 30 minutes a day for 5 days a week for 6 weeks.

• N = 157   
• MEAN AGE = 54.77 years (SD = 8.62)
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Recruited from existing cohort of 682 breast cancer survivors with subjective cognitive complaints and Internet access

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Aarhus University Hospital, Denmark

PHASE OF CARE: Late effects and survivorship

Randomized, waitlist controlled, pretest–post-test design

• Paced Auditory Serial Addition Test (PASAT)-primary outcome working memory 
• Cognitive Failures Questionnaire (CFQ)-secondary outcome perceived cognitive function
• Neuropsychologic battery for other cognitive outcomes: Rey Auditory Verbal Learning Test (RAVLT) (verbal memory and learning), Digit Span Forward and Backward (working memory), letter fluency test
• 20 Question Test, and cognitive estimation task (CET) (executive function)
• Wechsler Adult Intelligence Scale (WAIS) (premorbid intelligence estimate)
• Beck Depression Inventory (depression)
• Whiteley-7 subscale from Common Mental Disorders Questionnaire (somatization, illness worrying, and conviction)
• SCL-ANX4 from Symptoms Checklist-92 of the Common Mental Disorders–Screening Questionnaire (anxiety)
• Likert-type scale rating of self-reported benefit from the intervention

Web-based cognitive training did not improve function for the PASAT-measured domain of working memory or the CFQ-measured secondary outcome of perceived cognitive function. Improvement was demonstrated for cognitive function on two other neuropsychologic measures for verbal learning (RAVLT) (F [2, 272.1] = 3.2, p = 0.043) and working memory (digit span backward) (F [2, 272.6] = 3.3, p = 0.04).

Primary and secondary outcomes were not achieved, but web-based cognitive training was associated with improvement onone test of verbal learning and one test of working memory. Further study with instruments validated for phone administration may be warranted.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable
• Not all measures were validated for phone administration.
• No webcam access to assure no cheating by participants

The web-based cognitive training intervention was well received by participants and not burdensome to administer in terms of costs. Small improvements were noted for some cognitive measures in the intervention group, and further study may be warranted.

To evaluate the feasibility of a cognitive rehabilitation intervention for persistent post-treatment cognitive issues in survivors of breast cancer and to conduct a substudy to garner preliminary data related to the use of quantitative electroencephalography (qEEG) to assess changes in cognitive function

Five weekly, manualized, two-hour sessions were provided to five cohorts of four to nine participants. The last cohort participated in the qEEG substudy. Two difficulty levels of in-class cognitive training and three levels of homework exercises were designed to build skills in the targeted areas of attention, executive function, and memory. Participants were encouraged to do four 20-minute sessions of homework exercises per week and log their time. Participants received a training manual workbook, CDs for auditory exercises, answer keys, and a stopwatch. In-class education focused on a specified targeted area and instructions on coping strategies to minimize anxiety (such as deep breathing, relaxation, pacing, and countering negative thoughts). Goal attainment was discussed during the group sessions to facilitate setting individual short-term and long-term goals. Neurocognitive testing, self-report instruments, and the qEEG (substudy) were administered at baseline (T0), within one week (T1), and at two (T2), and four (T3) months after completing the intervention.

• N = 27 (8 in substudy)  
• MEDIAN AGE = 54.1 years (SD = 6.3 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors within 18 months to five years after initial treatment completion who reported persistent cognitive issues that interfered with daily activities. Ongoing endocrine therapy and HER2-targeted adjuvant therapy were allowed. Inclusion requirements: 18–75 years old and stages 0–III breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Participants primarily were Caucasian, married, and well-educated (mean 16.4 years of education). The majority received chemotherapy (89%), radiation (63%), or endocrine therapy (67%). Exclusion criteria included untreated depression, psychiatric disorders, and disorders of the central nervous system (CNS) (i.e., CNS cancer, CNS treatment with intrathecal chemotherapy, surgery, radiotherapy, traumatic brain injury, seizures, intellectual disabilities, substance abuse disorder).

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: University of California, Los Angeles, United States

• PHASE OF CARE: Late effects and survivorship

Prospective trial

• CNS Vital Signs Computerized Testing Platform
  • Finger tapping dominant, finger tapping nondominant
  • Shifting attention test
  • Stroop reaction time
  • Continuous performance test
  • Symbol digit test
• Hopkins Verbal Learning Test, Revised (HVLT-R) (total recall, delayed recall)
• Brief Visuospatial Memory Test, Revised (BVMT-R)
• Trail Making Tests (TMT) A and B
• Paced Auditory Serial Addition Test (PASAT) Trial 1
• Judgment of Line Orientation (JLO) test
• Patient’s Assessment of Own Functioning Inventory (PAOFI)
• Beck Depression Inventory, Second Edition (BDI-II)
• Spielberger State-Trait Anxiety Inventory (STAI)
• Resting quantitative electroencephalography (qEEG)

PAOFI totals and memory complaint scores decreased between T0 and T1 (p = .031 and p = .009, respectively) and were maintained at T3 (p < .0001 in both). Decreases in high-level cognitive functions (PAOFI scale) were demonstrated at T3 (p = .005). Significant short- and long-term improvements were observed for the symbol digit, Stroop reaction time, and trail A tests (p < .05). Meaningful improvement by a reliable change index (RCI) occurred for 19% of patients (n = 5) between T0 and T1, and 30% of patients (n = 8) by T3. RCI improvement (in ≥ 2 of 16 tests) predominantly occurred for verbal learning and memory (HVLT-R), processing speed (symbol digit), and divided attention (shifting attention test). Absolute alpha power increase (qEEG) was associated with PAOFI improvements at T1 (p = .014). Change in alpha power correlated with change in PAOFI memory subscale at T1 (p = .021) and T2 (p = .004). Correlation also was noted with the PAOFI HLC subscale at T2 (p = .030) and T3 (p = .048).

This study's results demonstrated the feasibility of this cognitive rehabilitation intervention and preliminary evidence for the improvement of subjective and objective cognitive function. Larger randomized, controlled trials are necessary to further determine efficacy. Preliminary results supported the potential use of qEEG as a measure of change in cognitive function. An additional randomized, controlled trial is underway.

• Small sample (< 30)
• Risk of bias (no control group)
• Findings not generalizable
• Other limitations/explanation: Sample primarily was Caucasian, married, and well-educated. Results may not be generalizable to other demographics.

Cognitive rehabilitation interventions appear to be promising. Nurses should maintain an awareness of research results in this area and consider suggesting appropriate clinical trials to eligible survivors.

The purpose was to evaluate the efficacy of a cognitive rehabilitation intervention on self-report of cognitive dysfunction, performance on neuropsychological tests, and brain functioning.

Five weekly, manualized, two-hour sessions included two difficulty levels of in-class cognitive training and three levels of homework exercises that were designed to build skills in the targeted areas of attention, executive function, and memory. Participants were encouraged to do four 20-minute sessions of homework exercises per week. Participants received a training manual workbook, auditory exercises CDs, answer keys, and a stopwatch. In-class education also included instruction on coping strategies to minimize anxiety (e.g., deep breathing, relaxation, pacing, countering negative thoughts). Goal attainment was discussed during the group sessions to facilitate setting individual short-term and long-term goals. These specific intervention details were published in 2013 with the results of the single-arm pilot study and not iterated in the 2015 article. Neurocognitive testing, self-report instruments, and qEEG (substudy) were administered at baseline (T0), within one week (T1), and two (T2) and four (T3) months from completing the intervention.

• N = 48; 29 in EEG substudy   
• AGE: mean = 53.8 years, SD = 8.2
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors within 18 months to 5 years after initial treatment completion who reported persistent cognitive complaints that interfered with daily activities and scored at least one item on the memory scale of the PAOFI as moderately severe. Ongoing endocrine therapy was allowed. Inclusion requirements were within 21-75 years of age and stage 0-III breast cancer. 
• OTHER KEY SAMPLE CHARACTERISTICS: Participants primarily were Caucasian (90%), married (79%), well educated (54% had postcollege degrees), status postchemotherapy (77%) and radiation therapy (75%), and were currently receiving endocrine therapy (71%). Exclusion criteria included uncontrolled depression, current psychiatric disorder, chronic concurrent use of psychoactive medications, central nervous system (CNS) disorders, previous intrathecal chemotherapy or cranial radiation, previous head trauma, seizures, or learning disability, or substance abuse disorder.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: UCLA, Los Angeles, CA

PHASE OF CARE: Late effects and survivorship

Randomized, wait-list controlled, interventional study. Powered on previous single-arm pilot study. Used block randomization (2:1). Intent-to-treat analyses

CNS vital signs computerized testing platform

•     Finger tapping dominant, finger tapping nondominant
•     Shifting attention test
•     Stroop reaction time
•     Continuous performance test
•     Symbol digit test

Rey Auditory Verbal Learning Test (RAVLT) 

Brief Visuospatial Memory Test, Revised

Verbal fluency test

Trail Making Tests A and B

Paced Auditory Serial Addition Test

Wechsler Test of Adult Reading (WTAR)

Patient’s Assessment of Own Functioning Inventory (PAOFI)

Beck Depression Inventory, 2nd edition (BDI-II)

Awake and resting state quantitative electroencephalography (qEEG)

Improvement in PAOFI total scores and memory scale scores were significant for the intervention group (p = 0.01, Effect size (ES) 0.90 and 1.10 respectively). The intervention group improved on RAVLT total scores (trials I-V, p = 0.02, ES = 0.57) and delayed recall (p = 0.007, ES = 0.29). Both groups improved on BDI-II scores at T2 and T3 without significant group differences. The qEEG substudy demonstrated intervention group changes (T1 to T2) for global absolute delta power (p = 0.02) and absolute alpha power (AP, p = 0.04). Decreased delta power did not predict PAOFI improvement at T2 (p = 0.971), nor did increased AP (p = 0.137). However, increased AP predicted improved self-report of cognitive dysfunction at T3 (p = 0.012), even controlling for age and IQ (p = 0.011).

The intervention was associated with improved self-report of cognitive function and neuropsychological test performance sustained up to two months. The qEEG substudy demonstrated preliminary evidence of an overall decrease in delta power and increase in AP for the intervention group, suggesting qEEG may serve as a biomarker of intervention efficacy.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable

Study findings provided further evidence that cognitive rehabilitation is beneficial to improving perceived and actual cognitive function in breast cancer survivors. qEEG may be promising as an early biomarker of intervention effectiveness.

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.

To evaluate the effectiveness of small group neurocognitive training to improve cognitive impairment in patients with brain tumors

Pre- and post-intervention cognitive testing was performed. The 10-week-long intervention consisted of 90-minute weekly group sessions of holistic mnemonic training, which included exercises to train perception, concentration, attention, memory, retentiveness, verbal memory, and creativity.

• A total of 11 patients were enrolled in the study.
• Participants' ages ranged from 23–73 years (median = 50 years).
• The sample was 64% male and 36% female.
• Patients had been diagnosed with glioblastoma multiforme (n = 6) or anaplastic gliomas (n = 5).
• Time since initial diagnosis ranged from 10–42 months (median = 15 months).
• Every participant had received treatment that included surgery, radiation therapy, and adjuvant chemotherapy with temozolomide. One subject also received hydroxyurea and imatinib in addition to temozolomide.
• Three subjects had tumor recurrence 3–28 months prior to study participation; none underwent additional surgery, and further treatment with radiation or chemotherapy was not provided. 
• All subjects were taking antiepileptic medications; however a variety of drugs were used. 
• Subjects varied in professional and educational background, but actual information was not provided.

• Single site
• Outpatient setting
• Vienna, Austria

• Patients were undergoing long-term follow-up.
• The study has applicability for late effects and survivorship.

Pilot study with pre-/post-test design

• Trail Making Test–A (TMT-A)    
• Trail Making Test–B (TMT-B)
• Hopkins Verbal Learning Test (HVLT)
• Controlled Oral Word Association Test (COWAT)

Although comparison of mean group differences found improvement in all neuropsychological tests, separate dependent t-tests revealed statistically significant improvement only in verbal memory total learning (p < 0.05) as measured by the HVLT. Significant improvement was not seen in verbal memory delayed recall (p = 0.11) as measured by the HVLT, psychomotor speed (p = 0.22) as measured by the TMT-A, sustained attention (p = 0.17) as measured by the TMT-B, or verbal fluency (p = 0.29) as measured by the COWAT.

Significant improvement was found in verbal memory (total learning). However, it is not possible to distinguish whether the improvement was a benefit of the intervention or resulted from practice effects associated with the repeated measures occurring 12 weeks from baseline. Additionally, any assumptions regarding effectiveness of the intervention would need to be supported by a larger sample with an appropriate comparison control group.

• The sample was small, with less than 30 participants.
• The lack of a comparison control group or randomization limited the generalizability of results and the feasibility of the intervention.

Although neurocognitive training has been suggested as a potential intervention for cognitive impairment, further studies are needed (including feasibility). Effectiveness of this intervention cannot be established based on this pilot study.

To test the feasibility and effectiveness of a computerized home-based cognitive intervention program

Subjects were randomly assigned to the intervention group or a wait-list control group. The intervention was a 12-week computerized training program (Lumos Labs) using the subjects' home computers. It included 48 sessions that were 20-30 minutes long, involving combinations of 13 exercises to improve executive function. Subjects were assigned five exercises to complete four times per week. Exercises were designed for practice and training in cognitive flexibility, working memory, processing speed, and verbal fluency.  Completion, duration and performance of exercises were recorded in the computer system, providing an adherence measure. Outcome measures were collected at baseline and within three days of intervention completion; wait-list controls had pre-post measures taken 12 weeks apart.

• N = 41    
• MEAN AGE = 55.5 years (SD = 0.5 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All subjects had stage I-IIIA  breast cancer, received surgical intervention and adjuvant chemotherapy, and completed treatment at least 18 months prior to study participation.
• OTHER KEY SAMPLE CHARACTERISTICS: Subjects had at least a high school education; 60%-70% also received radiation therapy and hormonal therapies.

• SITE: Single site    
• SETTING TYPE: Home  

PHASE OF CARE: Late effects and survivorship

Randomized controlled trial

• Wisconsin Card Sorting Test (WCST)
• Delis-Kaplan Executive Functions System, Letter Fluency Test
• Hopkins Verbal Learning Test Revised
• Wechsler Adult Intelligence Scale (digit span and symbol search subscales)
• Behavioral Rating Inventory of Executive Function (Global Executive Composite score)
• Clinical Assessment of Depression

There was 95% compliance with the training program. The intervention group had significant improvement as shown by Cohen’s d, the WCST (EF = 0.58, P = .008), the Letter Fluency Test (EF = 0.82, P = .003), and symbol search (EF = 0.87, P = .009). While there were no significant effects of age, education, radiation, or hormonal treatment, presence of depressive symptoms had a significant effect on self-reported global executive function.

This approach for training and home-based exercises is feasible, and compliance was high. The program was effective for improving some components of executive function. Further study with longitudinal measures is warranted to demonstrate maintained improvements in cognitive function after program completion or if continued program use is needed to maintain any improvements.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Intervention expensive, impractical, or needs training
• The computerized training cost was covered by the research study; however, it is commercially available for individual cost, which may be an issue for some patients. The sample was a homogenous group of patients, potentially limiting generalizability to other patient groups.

The commercially available computerized “brain training” program studied here improved components of executive function after 12 weeks. This approach was associated with high patient compliance. Nurses can suggest that patients complaining of cognitive impairment consider trying this program.

Randomized, wait-list controlled study conducted to evaluate the efficacy of a web-based cognitive rehabilitation therapy (CRT) program for adults with non-central nervous system tumors and cognitive complaints.

The web-based CRT program (eReCog) was adapted from an in-person manualized format (ReCog). Participants completed four 30- to 60-minute online modules (one each week). Learning techniques involved psychoeducation, relaxation, strategy training, and homework. On-line discussion and questions were anonymized. The program content included (a) ageing, health, cancer, cognitive function, (b) memory, (c) attention, (d) fatigue, emotions, and cognition. Module links were emailed to participants. Participant module progression was tracked. Module completion triggered receipt of the next consecutive module. Feedback on individualized goal setting (after Module 1) was provided via email. On-line questionnaires were administered at baseline, four weeks, and three months. Primary endpoint: perceived cognitive impairment. Secondary endpoints: objective cognitive function, psychosocial variables.

• N = 71   
• MEAN AGE: 56.01 years (extrapolated from report of separate group means. No range reported)
• FEMALES: 71%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Non-central nervous system adult on-set (18 years or older) malignancies; at least 6 months post-primary treatment. 
• OTHER KEY SAMPLE CHARACTERISTICS: Complaints of memory or concentration issues participants attributed to their cancer experience. Concurrent endocrine therapy allowed. Exclusion for history of traumatic brain injury, neurological disorder, or uncontrolled anxiety or depression. Fluency in English required.

• SITE: Multi-site   
• SETTING TYPE: Home    
• LOCATION: Investigators were based at two academic centers (Australia and China), but demographics related to participants’ location is not reported.

PHASE OF CARE: Late effects and survivorship

Randomized, wait-list controlled design. Powered to detect small to moderate interaction effects (80% power, alpha = 0.05) with 20% added to account for attrition (goal: n = 65).

• Functional Assessment of Cancer Therapy-Cognitive Scale (FACT-Cog-3)
• Brief Assessment of Prospective Memory Instrumental Activities of Daily Living (IADL) subscale
• WebNeuro (online test battery for verbal and working memory, attention, response speed, information processing efficiency, executive function, impulsivity)
• Kessler Psychological Distress Scale
• Brief Illness Perception Questionnaire (BIPQ)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) fatigue symptom scale

Intervention group reported significant reduction in prospective memory failures post-intervention (p = 0.005) and three months (p < 0.001). Wait list-controls reported a significant reduction at three months (p = 0.02). Intervention group demonstrated clinically meaningful improvement for FACT-Cog PCI subscale scores (minimally important difference > 6.5, actual improvement 8.9 versus 5.6 for controls) post intervention.

Within-group improvement noted for intervention group on FACT-Cog PCA subscale post intervention (p = 0.002, d = 0.3) and three months (p = 0.007, d = 0.42). Controls improved at three months (p = 0.032, d = 0.22). Intervention group reported decrease in impact of cognitive issues on QOL post-intervention (p = 0.007, d = 0.26) and three months (p = 0.005, d = 0.56). Controls reported decreased impact at three months (p = 0.04, d = 0.24). No interactions were noted for objective neurocognitive measures, distress, or BIPQ. Fatigue was reduced postintervention for the intervention group (p = 0.046, d = 0.27), but not at three months. Participants’ satisfaction ratings were high (94%), and 68% reported “a little or a lot” of improvement in cognitive function.

Preliminary evidence demonstrated in support of this web-based CRT (eReCog) as an effective intervention for self-reported issues with cognitive function following primary treatment for breast cancer. Feasibility and satisfaction demonstrated for use of this web-based CRT.

• Small sample (< 100)
• Risk of bias (no blinding)
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: No supervision for completion of study questionnaires may allow unknown influences and/or interruptions. Sample was 100% female and 98.5% breast cancer; therefore, generalization of findings is limited. Statistical analyses included multiple comparisons. Group allocation was made following initial expression of interest and participants were informed of group allocation at the time consent confirmation was secured via email. In addition, participants’ knowledge of the expected outcome for the intervention may have induced some placebo effect.

Future research with a larger sample size is needed to confirm the impact of web-base CRT (on both subjective and objective measures of cognitive function) in the breast cancer survivor population. Web-based CRT has the potential to increase access and decrease cost/burden associated with intervention delivery.

To investigate the neural correlates of semantic strategic training in patients with distinct prefrontal cortex lesions

In the 30-minute semantic organizational strategy training, subjects were taught three steps to improve memory: (1) organize words into categories, (2) memorize words, and (3) retrieve words by category. Subjects were required to undergo a minimum of five training trials and to demonstrate that they had learned how to apply the semantic organizational strategy. Pre- and post-test evaluations consisted of subjects undergoing functional magnetic resonance imaging (fMRI) scanning immediately prior to and after the semantic strategy training.

• N = 21      
• MEAN AGE = 45.7 years for bilateral orbitofrontal cortex (BOFC) patients and 39.57 years for dorsolateral prefrontal cortex (LPFC) patients
• MALES: 57%, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: 21 patients with confirmed primary brain tumor (PBT) located in the prefrontal cortex, specifically the LPFC or BOFC
• OTHER KEY SAMPLE CHARACTERISTICS: At least six months post-chemotherapy and radiation therapy; time since surgical resection ranged from 6 months to 10 years (mean = 2.65 years; SD = 2.4 years); all subjects were non-aphasic, right-handed, and free of other neurological or psychiatric conditions.

• SITE: Not stated/unknown  
• SETTING TYPE: Not specified    
• LOCATION: Not stated but ethics approval was received from the University of Sao Paulo Medical School.

Exploratory study using a pre- and post-test design in a convenience sample

• 3 word lists of 16 words each: unrelated and related non-structures, and related structure word lists for cortical activation during scanning
• fMRI scan

Both subject groups recalled more words (p < 0.001) and organized more words together (p < 0.001) after semantic training. For the BOFC group, there were significant differences (p < 0.01) after the intervention of increased activation: (1) right cuneus and posterior cingulate gyrus, and left precuneus during the related structure word list trial and (2) left precentral gyrus, postcentral gyrus, inferior frontal gyrus, and insula during the unrelated word list trial. For the LPFC group, there were significant differences (p < 0.01) after the intervention, in multiple cortical areas: (1) increased activation in the left inferior frontal gyrus, precentral gyrus, and insula during the related non-structured word list trial (2) increased activation in the left inferior frontal gyrus, precentral gyrus, and anterior cingulate during the related structure word list trial, and (3) decreased activation in the left supramarginal gyrus, precuneus, superior temporal gyrus, and superior parietal lobe during the related structure word list.

The intervention increased use of categorizing words, thereby improving memory performance in subjects with prefrontal PBT. Changes in cortical activation suggest intervention application and recruitment of compensatory brain mechanisms for memory tasks. Further study with longitudinal measures is warranted to demonstrate continued cortical activation and intervention application during memory tasks.

• Small sample (< 30)
• Risk of bias (no control group)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: fMRI scanning for pre- and post-measures is expensive, is impractical, and requires specialized training and equipment. This study was performed in a homogenous sample.

This study demonstrated the application of a quick single session semantic training intervention aimed at improving verbal memory performance in those with known neuropathology.

The study was conducted to evaluate the need of patients with breast cancer for neuropsychological rehabilitation after adjuvant chemotherapy. It also sought to determine the effectiveness of differentiated training programs after completion of treatment.

Participants were randomly assigned to one of two intervention groups. Control participants were selected from the “time-out” phase of the study when no training was being offered.

Both intervention groups took part in four one-hour training sessions per week during their inpatient stay. Participants were randomized to one of the following outpatient interventions.

1. Neuropsychiatric Training Group (NPT). A maximum of eight participants met with a specialized occupational therapist to work on improving attention and memory through situations specifically designed to reflect the demands of everyday life. They received practice in compensational strategies and specific techniques to improve their performance in these everyday situations, and reflected on their personal experiences.
2. Computer-based training (PC). Participants received individualized computer-based training with continuous therapeutic supervision. The software addressed specific attention and memory dimensions in eight modules. Following the PC training, participants also received individualized coaching according to their specific impairments.

Measures were completed upon admission to the rehabilitation unit (T1), at the end of in-patient rehabilitation (T2), and six months later on an outpatient basis (T3). 

• The number of participants was 90.
• All participants were female.
• All participants had breast cancer, with an average of 9.01 months since diagnosis and 2.06 months since the conclusion of chemotherapy.
• There were 33 participants in the NPT intervention group, 32 in the PC intervention group, and 25 in the control group.
• The average participant age was 49.19 ± 7.71 years.
• 16.7% of participants had a university degree, with only 3.1% not professionally trained.
• Participants were predominately receving chemotherapy with anthracyclines; most had postoperative localized radiation therapy and adjuvant antihormonal therapy.
• Individuals were exclused from the study if they were older than 64 years; had psychiatric mental health disorders or other cancer, psychiatric, or neurologic problems; or were currently using psychoactive medications.

The study took place at the Tumor Biology Center Rehabilitation Unit in Freiburg, Germany.

The study utilized a randomized, controlled trial.

• Questionnaire of Self-Perceived Deficits in Attention (FEDA) for attention
• Test Battery for Attentional Performance (TAP) for attention
• Digit Span for attention
• Wechsler Memory Scale-Revised for memory
• Rivermead Behavoral Memory Test (RBMT) Immediate and Delayed Story Recall for memory
• Learning and Memory Test (LGT-3) for memory
• Multidimensional Fatigue Inventory (MFI) for mental fatigue, activity, and motivation
• Hospital Anxiety and Depression Scale (HADS) for anxiety and depression
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - 30 (EORTC QLQ-30) for global and functional quality of life. The EORTC QLQ-30 uses six subscales (global, physical, role, cognitive, emotional, social functioning). Scores range from 0–100, with higher scores indicating higher quality of life.

No intervention effects were noted in this study. Significant improvement was noted in 11 of 16 neuropsychiatric parameters for all three groups between T1 and T2. Forty participants (44.4%) maintained at least one cognitive deficit at five months; 19 (21.1%) maintained two or more deficits at T3.

Both intervention groups received similar amounts of training sessions. Eighty-four participants (87.5%) had at least one impaired neuropsychological parameter and 54 (56.2%) had two or more at baseline.

No significant differences in cognitive ability between treatment groups were reported.

• The study lacked a clear description of the PC intervention.
• The use of an inpatient setting and the timing of interventions may have affected the outcome.
• The study did not address practice effects with repeated testing over time.

To evaluate the efficacy of memory and speed of processing training for improving cognitive function in breast cancer survivors

Patients were randomly assigned to one of three groups: training in speed of processing, memory training, or a wait list control group. The intervention included 10 one-hour sessions of memory and speed of processing training delivered in small groups of three to five patients over six to eight weeks. Specific intervention strategies were adapted from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trials. Follow-up was done at two months.

• A total of 82 patients participated in the study.
• Participants' mean age was 56.6 years (SD = 8.5 years).
• The sample was 100% female.
• All patients were diagnosed with breast cancer and had received surgery and chemotherapy. The mean time since treatment was 5.5 years.

• Single site
• Outpatient setting
• United States

Patients were in the late effects and survivorship phases of care.

Single-blind, three-group randomized controlled trial

• Rey Auditory Verbal Learning Test
• Rivermead Behavioral Paragraph Recall test
• Useful Field of View for speed of processing
• Functional Assessment of Cancer Therapy–Cognitive (FACT–Cog)
• Squire Subjective Memory Questionnaire
• Center for Epidemiological Studies Depression Scale
• Spielberger State–Trait Anxiety Inventory
• FACT–Fatigue
• Quality of Life Cancer Survivors
• Short Form-36

The memory training group demonstrated better immediate (d = 0.59, p = 0.036) and delayed memory performance (d = 0.70, p = 0.013) at the two-month follow-up compared to the control group. Those trained in speed of processing improved immediate memory post-intervention (d = 0.75) and at the two-month follow-up (d = 0.82) (p < 0.01). The memory and speed of processing training groups had significant improvement in perceived cognitive functioning on questionnaires. Compared to controls, speed of processing training was associated with lower symptom distress. Memory training also had a positive effect on anxiety at the two-month follow-up (p = 0.017)

Memory and speed of processing training had significant positive effects on objectively measured and perceived cognitive function among female breast cancer survivors.

• The sample was small at less than 100.
• A lack of blinding and no appropriate attentional control condition introduced a risk of bias.
• The findings not generalizable because of the highly specific sample group. The findings may not be applicable to other groups of patients or at other time points in the cancer trajectory.
• The training needs to be delivered by individuals educated in the process.

Cognitive training as provided here had a significant and at least a moderate positive effect on cognitive function in breast cancer survivors. Cognitive deficits with cancer treatment have substantial negative impacts on quality of life and functioning. Cognitive training is a promising intervention to address these problems.

The purpose of this pilot study is to examine the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training program compared to usual care in patients with breast cancer on androgen deprivation therapy (ADT).

BrainHQ, one hour per day, five days per week for eight weeks or 40 hours total

• N = 60    
• AGE: 66.6 years (SD = 8.5)
• MALES: 60 (100%)  
• FEMALES: 0 (0%)
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients with prostate cancer who had received three or more months of ADT 
• OTHER KEY SAMPLE CHARACTERISTICS: 55 (91.7%) were White, well-educated (16.5, SD = 2.8 years) with 24 (40%) annual household income of $110,000 or greater and on average 6.9 years (SD = 5.5) time since diagnosis, and 45.7 months (SD = 49.7) of ADT.

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: Mount Sinai Hospital, New York

PHASE OF CARE: Late effects and survivorship

This was a two-group pilot study which randomized patients with prostate cancer who had been on ADT three months or longer to BrainHQ or usual care. Patents were screened and outcomes assessed at three time points: baseline (T1), immediately after 8 week intervention (T2), and 8 weeks later (T3). Participants were asked to complete 40 hours of training over 8 weeks.

• Feasibility (%) randomized and completed study
• Acceptability: 8-item Client Satisfaction Questionnaire
• CNS Vital Signs (30-minute computer administrated neuropsychological assessment for basic-level functions (reaction time, simple attention, processing speed, and motor speed) and higher-level functions (verbal memory, visual memory, and cognitive flexibility). 
• Patient Assessment of Own Functioning Inventory: 33-item self-report scale

87 of 174 (50%) were screened and consented. 73 completed baseline and 60 met randomization criteria. Retention was 72.5% for intervention and 100% in usual care at T2 and 72.5% and 100% in usual care at T3. 
Overall, 50% randomized; however, less than 70% completed the study (10 hours or greater total of the intervention, results were greater than 70% if non-completers of the intervention were included. Participants were mostly satisfied with training (2.97, SD = 0.53 on scale of 1-4 with 4 being most positive). Most common barriers to training included difficulty finding time to train (n = 16, 52%), tiredness (39%), health problems (35%), boredom (32%), and distraction (16%). Preliminary efficacy of training was mixed: improvement noted in reaction time (p = 0.01); however, was unfavorable on verbal and visual memory. Memory was temporarily suppressed in the training group at T2 but normalized at T3. No effect of training noted on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life.

This study presented tentative support for the feasibility and acceptability of BrainHQ in prostate cancer patients. Preliminary efficacy of BrainHQ was mixed with improvement in reaction times but more research is needed to fully understand efficacy of cognitive training.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: A number of participants did not complete the minimum training requirements of ≥ 10 hours of training over the 8-week period.

Cognitive training using BrainHQ may be feasible and mostly satisfying intervention for prostate cancer survivors. Additional studies are needed to determine efficacy.

To evaluate the effectiveness of a cognitive rehabilitation program within two weeks of surgical resection for patients with primary brain tumors

Baseline neuropsychological assessments were performed within three days of admission to the inpatient rehabilitation unit and prior to treatment or control randomization. Treatment arm consisted of 16 one-hour individual sessions over a four week timeframe with content focused on time orientation, spatial orientation, visual attention, logical reasoning, memory recognition, and executive functions. Each session was therapist-guided with 45 minutes of computer-based exercises and 15 minutes of discussion about the exercises and how to apply the strategies to everyday life. In both arms of the study, patients received usual rehabilitation care with medication and physical therapies.

• N = 53    
• MEAN AGE: 58.7 years (treatment group), 52.7 years (control group)
• MALES: 56%, 47%, FEMALES: 44%, 53%
• KEY DISEASE CHARACTERISTICS: Two weeks post-neurosurgical primary brain tumor patients with no prior exposure to radiation or chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria required cognitive deficits on a minimum of three neuropsych tests.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Neurological Mediterranean Institute

PHASE OF CARE: Active antitumor treatment

Randomized double-blind control trial with pre- and post-test assessments at baseline and four weeks after randomization

• Mini-Mental State Exam for global cognition
• Digit Span and Corsi’s test for verbal and spatial immediate memory span
• Rey auditory verbal learning test (RAVLT), immediate recall (IR) and delayed recall (DR), for verbal memory  
• Logical memory, IR and DR, for verbal memory
• Raven’s Coloured Progressive Matrices 47 for non-verbal reasoning
• Frontal assessment battery for frontal functionality
• Trials Making Test Parts A & B (TMT-A and TMT-B) for processing speed and complex attention
• Attentive Matrices for visual selective attention
• Rey-Osterrieth Complex Figure Copy Test for visuo-constructional abilities and verbal fluency
• Esame Neuropsicologico per l’Afasia for expressive and receptive language abilities

Within-group analyses found significant improvements (p < 0.05) on all neuropsychological tests for the treatment arm, while the control arm showed a non-significant trend towards improvement. Significant differences between groups were observed for improvements in visual attention and verbal memory (RAVLT-DR, Logical memory-IR and DR, TMT-A, TMT-B, Attentive matrices). There was no difference between groups in the socio-demographic, clinical characteristics, or baseline neuropsychological test scores. There was no difference between groups for number of subjects withdrawing from study due to medical conditions.

This inpatient cognitive rehabilitation program was developed for patients with a post-surgical primary brain tumor. Those receiving the intervention showed significant cognitive improvement in all domains, yet only visual attention and verbal memory performances were significantly different when compared to usual rehabilitation care. These results are limited by sample size, lack of additional longitudinal assessments to demonstrate sustained improvement, and program cost.

• Small sample (< 100)
• Findings not generalizable
• Intervention expensive, impractical, and needs training
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Only one post-test assessment immediately following completion of intervention occurred, thus lacking demonstration of sustained cognitive improvement. Findings not generalizable due to cost of inpatient rehabilitation program, which would need adapting for use in outpatient settings.

Post-surgical cognitive interventions may be helpful in developing cognitive strategies for everyday function. Further study is warranted and intervention adaptation is necessary for outpatient settings.