It’s about time: mitigating cancer-related cognitive impairments through findings from computational models of the Wisconsin Card Sorting Task

Effectiveness of computerised cognitive training on cognitive functioning and quality of life in cancer survivors with cancer-related cognitive impairments: A systematic review and meta-analysis.

Advances in cancer diagnosis and treatment have substantially improved patient outcomes and survival in recent years. However, up to 75% of cancer patients and survivors, including those with non-central nervous system (non-CNS) cancers, suffer from “brain fog” or impairments in cognitive functions such as attention, memory, learning, and decision-making. While we recognize the impact of cancer-related cognitive impairment (CRCI), we have not fully investigated and understood the causes, mechanisms and interplays of various involving factors. Consequently, there are unmet needs in clinical oncology in assessing the risk of CRCI and managing patients and survivors with this condition in order to make informed treatment decisions and ensure the quality of life for cancer survivors. The state-of-the-art neuroimaging technologies, particularly clinical imaging modalities like magnetic resonance imaging (MRI) and positron emission tomography (PET), have been widely used to study neuroscience questions, including CRCI. However, in-depth applications of these functional and molecular imaging methods in CRCI and their clinical implementation for CRCI management are largely limited. This scoping review provides the current understanding of contributing neurological factors to CRCI and applications of the state-of-the-art multi-modal neuroimaging methods in investigating the functional and structural alterations related to CRCI. Findings from these studies and potential imaging-biomarkers of CRCI that can be used to improve the assessment and characterization of CRCI as well as to predict the risk of CRCI are also highlighted. Emerging issues and perspectives on future development and applications of neuroimaging tools to better understand CRCI and incorporate neuroimaging-based approaches to treatment decisions and patient management are discussed.

The specificity of the Wisconsin Card Sorting Test (WCST) for assessing frontal lobe pathology remains controversial, although lesion and cerebral blood flow studies continue to suggest a role for the dorsolateral prefrontal cortex in WCST performance. Inconsistencies might derive from the extended use of various WCST scores as equivalent indicators of frontal pathology. In this study, event-related potentials (ERPs) were recorded from 32 normal subjects who committed perseverative and non-perseverative errors. Both types of WCST errors evoked anomalous but distinct ERP patterns over frontal lobe regions. Perseverative errors were also associated with a dysfunctional extrastriate response to stimulation. This evidence suggests that perseverative and non-perseverative errors result from disruptions in two different prefrontal neural networks engaged during card sorting.

Background: Although studies have indicated that the frontal lobe plays an important role in performance on the Wisconsin Card Sorting Test (WCST) and that basal ganglia play a specific role in frontal lobe function, the role of striatal dopamine (DA) activity in performance on the WCST remains unclear. Methods: We assessed the relation between the availability of striatal dopamine transporters (DATs) and performance on the WCST as a measure of executive function in healthy individuals. We approximated the availability of DATs in 53 healthy volunteers aged 19–61 years by use of single photon emission computed tomography with technetium-99m (99mTc)-TRODAT-1 as the ligand. The WCST was administered to all participants. Results: The availability of DAT was significantly negatively correlated with perseverative errors on the WCST, both before and after adjustment for body mass index ( rbefore = −0.39, p = 0.004; rafter = −0.39, p = 0.005). Limitations: This was an association study; thus, a causal relation between DAT availability and performance cannot be confirmed. Conclusion: Our results suggest that striatal DAT availability may play a role in executive function as measured by the WCST.

Objective To investigate the cognitive impairment in depression with anxiety symptom and its influencing factors. Methods 458 first-episode depression patients were assessed with Hamilton Anxiety Scale (HAMA). According to the score of HAMA, the patients with depression were divided into with anxiety symptom group (n=266) and without anxiety symptom group (n=76). Using Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess neuropsychological function. Results (1)The group without anxiety symptom had higher scores on categories completed(2.88±2.14), learning to learned(64.16±24.20), immediately memory(81.78±17.16), visual span(84.08±15.41), attention(106.45±20.72) and delayed memory (86.12±13.06) than the group with anxiety symptom had((2.07±1.98), (54.33±27.05), (70.47±17.61), (79.76±14.63), ( 98.25±17.11), (79.97±16.10) respectively), and all these differences were significant (P<0.01 or P<0.05). The group without anxiety symptom had lower scores on response error(61.21±21.50), perseverative error percentage(17.11±6.10), monochrome time(19.04±6.57), time of meaning interference(15.01±9.11) and time of color interference(2.79±2.82) than the group with anxiety symptom had((67.20±21.87), (19.21±7.18), (21.03±7.69), (17.92±10.64), (3.86±5.61)respectively), and all these differences were significant (P<0.05). (2)The combination of educational years, age, somatic anxiety and psychic anxiety explained the 28.1% variances of immediately memory(F=25.015, P<0.01); the combination of educational years and psychic anxiety explained the 19.8% variances of delayed memory(F=31.625, P<0.01); and the combination of age and psychic anxiety explained the 13.6% variances of time of meaning interference(F=20.293, P<0.01). Conclusion Depression with anxiety symptom has more severe impairment on executive function, processing speed, memory and attention.Educational years, age, psychic anxiety and somatic anxiety are influencing factors. Key words: Depression; Anxiety symptom; Neuropsychological function

The dual theory establishes that the decision-making process relies on two different systems, the affective system and the executive function (EF), developed during adolescence. This study analyzes the relationship between the decision-making and EF processes in a group of early adolescents (mean age = 12.51 years, SD = 0.61), where more affective impulse processes are developed, and in young adults (mean age = 19.38 years, SD = 1.97), where cognitive control processes have already matured. For this purpose, 140 participants in Spain completed the Iowa Gambling Task (IGT) to measure their risky decisions and the Wisconsin Card Sorting Task (WCST) to measure their EF. Performance on the IGT improves over blocks; however, adolescents received lower mean scores than young adults. However, controlling for age, perseverative errors were negatively associated with the mean net score on the risky blocks of IGT; thus, those who committed more perseverative errors in the WCST were more likely to take cards from the disadvantageous decks on the last blocks of the IGT. The current study shows that adolescents and adults solve ambiguous decisions by trial and error; however, adolescents are more likely to make risky decisions without attending to the long-term consequences. Following the dual theory hypothesis, the maturation of EF with age partly accounts for this difference in risky decision-making between adolescents and adults.

Cancer-related cognitive impairment is a broad term encompassing subtle cognitive problems to more severe impairment. The severity of this impairment is influenced by host, disease, and treatment factors, and the impairment affects patients before, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a clinical trial planning meeting to review the state of the science on cancer-related cognitive impairment and develop phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of cancer-related cognitive impairment, members of the SxQoL SC, patient advocates, representatives from all 7 NCI Community Oncology Research Program research bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacological and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three clinical trial planning meeting working groups (longitudinal studies as well as pharmacological and behavioral intervention trials) convened for 1 year to discuss and report on top priorities and to design studies. The meeting experts concluded that sufficient data exist to advance phase II/III trials using selected pharmacological and behavioral interventions for the treatment of cancer-related cognitive impairment in the non-central nervous system setting, with recommendations included herein.

There is a steep linear increase in patients surviving a cancer diagnosis. Clinical solutions that address the high prevalence of cancer-related treatment effects (CRTE) are urgently needed. A stark example of this need is the dearth of screening and treatment programs for cancer related cognitive impairment (CRCI) (colloquially called “chemo-brain”). Up to 75% of cancer patients report neurocognitive changes that leave patients unable to cope with the expectations of employers, colleagues, families, and friends. The prevalence of neurological disorders is 275% higher among adult cancer patients, when compared to an adult cancer-free population. For many adolescent and young adult cancer patients, the onset of CRCI occurs during "cognitive prime time"; a time when individuals are pursuing education, careers, and raising families. To address a gap in CRTE we have implemented a virtual multi-disciplinary intervention to measure and treat CRCI. Our CRCI intervention follows National Comprehensive Cancer Network and American Society of Clinical Oncology (ASCO) guidelines for CRCI. These guidelines indicate a multi-disciplinary approach with emphasis on increasing physical activity levels, cognitive-behavioral therapy, memory adaptive training, mood management, and sleep optimization. Our approach also follows recent ASCO guidelines for nutrition counseling. Our CRCI program utilizes medical oncologists, physician assistants, mental health therapists, registered dietitians, and occupational therapists. A nationally validated patient reported outcome (PRO) measurement, analysis, and reporting platform informs clinical treatment pathways, monitors patient progress, guides clinical decision making, and improves patient/provider communication. Using health status measures for CRCI, and following American Cancer Society and ASCO guidelines, patients are risk-stratified into three personalized cancer survivor care pathways: 1) low-complexity patients; 2) medium-complexity patients; and 3) high-complexity patients. Low-complexity patients baseline PROs score in the normal range, medium-complexity patients are those who score below the norm (moderate to large effect size difference from normal), and high-complexity patients are those who score well below the norm (greater than larger effect size difference from normal). Low-complexity patients are enrolled into a self-management and continuation of care program. Medium-complexity patients are enrolled into a shared care program. High-complexity patients are enrolled into an acute care program. All three clinical pathways include continued risk-factor vital-sign surveillance. Nearly 100% (99%) of patients who enroll in our primary cancer survivor care program complete our PRO baseline (N=80). From a convenient sample of breast cancer patients (N=42), provisional results of patient-specific segmentation analyses reveal a nearly perfect bell-shaped curve, with 51% of the population classified within the definition of medium-complexity and even split of outliers (high-complexity 24% and low-complexity 24%). Additionally, of all patients in our primary cancer survivor care program who completed at least three measurement time points for health status measures of cognitive impartment (N=38), 92% had a positive experience, 71% had a clinically significant improvement in cognitive health, 21% had a no change in cognitive status, and only 8% had a decline in cognitive health. If these data, and PRO implementation approach hold true, this program could be scaled to national and international cancer survivor population suffering from CRCI. Citation Format: John Librett, Mark Kosinski, Gregory Litton. Use of a standardized tool for the evaluation and treatment of cancer related cognitive impairment (chemo-brain) among breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-10.

Executive functioning and risk for Alzheimer's disease in the cognitively intact: Family history predicts Wisconsin Card Sorting Test performance.

Executive Function and Decision-Making in Women with Fibromyalgia

The aim of this study was to assess executive functions of obese individuals with binge eating disorder. Thirty-eight obese individuals with binge eating disorder were compared to thirty-eight obese controls without binge eating disorder in terms of their executive functions. All individuals were assessed using the following instruments: Digit Span, Trail Making Tests A and B, Stroop Test and the Wisconsin Card Sorting Test. In addition, four subtests from the Behavioral Assessment of the Dysexecutive Syndrome Battery were also used, namely the Zoo Map Test, the Modified Six Elements Test, the Action Program Test and the Rule Shift Cards Test. When compared to obese controls, obese individuals with binge eating disorder presented significant impairment in the following tests: Digit Span backward, Zoo Map Test, Modified Six Elements Test, and Action Program Test. Subjects with binge eating disorder also showed significant more set shifting and perseverative errors in the Wisconsin Card Sorting Test. In other measures such as the Digit Span Forward, the Trail Making Test, the Stroop Test and the Rule Shift Cards Test, obese subjects with binge eating disorder did not differ significantly from obese subjects without binge eating disorder. These results suggest that, in the present sample, obese individuals with binge eating disorder presented executive deficits, especially impairments relating to problem-solving, cognitive flexibility and working memory.

Objective To investigate the changes of the N-acetylaspartate(NAA) concentrations in different brain regions and executive function skills in alcohol dependence, and to study the relationship between NAA levels and cognitive functions in subjects. Methods 49 male, non-smoking, alcohol-dependent patients and 45 healthy control subjects were measured with Proton 1H Magnetic resonance spectroscopy (MRS) and Wisconsin Card Sorting Test (WCST). Results Alcoholics had lower NAA/Cr ratios in prefrontal grey matter(GM) (1.59±0.13) and white matter(WM) (1.58±0.12) regions and performed poorly on executive function tests compared to controls (P<0.001). NAA/Cr in left prefrontal regions positively correlated with certain parameters of EF testing (number of correct responses 30.37±3.73, perseverative errors 11.49±3.39, random errors 6.18±2.64, categories completed 2.08±1.59)in alcoholic group (P<0.01). NAA/Cr in prefrontal WM regions correlated with certain parameters of EF testing in alcoholic group (number of correct responses r=0.379, categories completed r=0.433, P<0.05). Conclusion Long-term, chronic alcoholism will damage neuronal viability and cognitive functions, which suggests that NAA concentrations can reflect the extent of damage of cognitive functions with decreased levels reflecting neuronal loss. Key words: Alcohol dependence; Magnetic resonance spectroscopy; N-acetylaspartate; Executive function

Background: Hypertension one of the main risk factors of cardiovascular diseases and premature death worldwide. Researches indicate different cognitive activities and executive functions in cardiovascular and hypertension patients compared to non-afflicted people. Objectives: Therefore, the purpose of this study was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) on executive functions in patients with hypertension. Materials &amp; Methods: The present study was a randomized clinical trial based on the pre-test, post-test, follow-up design. The statistical population consisted of all the people with hypertension who referred to Heshmat Heart Hospital in Rasht city, Iran, in 2021. Thirty-four qualified volunteers were included in the study by purposive sampling method and randomly assigned to two groups of MBSR and control. Wisconsin Card Sorting Test (computer version) were the instrument employed in this research; and MBSR sessions were held for 2 months (8 sessions, one 120-minute session each week). The research data were analyzed using repeated measures ANOVA and Bonferroni post-hoc test. Results: In the pre-test design, there wasn't a difference in the completed categories and perseverative errors, between the MBSR group (2±0.485 and 30.06±6.60) and the control group (2.06±0.659 and 29.88±9.4. In the post-test design, a significant difference in the completed categories and perseverative errors was found between the MBSR group (3.29±0.848 and 20.94±5.71) and the control group (2.18±0.636 and 29.94±8.70); which implies the MBSR group outperformed the control group in Improving executive functions of patients with hypertension. Finally, at the follow-up, all changes were still stable. Conclusions: MBSR was effective on executive functions of patients with hypertension. Therefore, it is suggested that the mentioned intervention be used in medical centres to improve the cognitive activities of patients with hypertension, so that its positive results include the condition of these patients.

Chapter 20 - Cancer-Related Cognitive Impairment: Diagnosis, Pathogenesis, and Management

Neuropsychologic profile of college students with schizotypal traits