Cancer-related Cognitive Impairment Research Articles

Effective non-pharmacological interventions for cancer related cognitive impairment in adults (excluding central nervous system or head and neck cancer): systematic review and meta-analysis.

Cancer-related cognitive impairment (CRCI) is prevalent in cancer survivors, and impairments affect daily living tasks and overall wellbeing. This review aimed to identify and evaluate published randomized controlled trials (RCTs) of interventions to manage CRCI in adult populations, to analyze their effectiveness and to investigate the quality of the studies. Seven databases were searched (Medline, Scopus, CINAHL, AMED, PsychINFO, OTseeker, and the Cochrane Database of Systematic Reviews), including years 2005-2020, for randomized controlled trials (RCTs) investigating interventions to address cognition for adults with cancer. The final search was conducted in February 2021. The quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for RCTs. Meta-analysis used comprehensive meta-analysis software. The study protocol was registered with PROSPERO (registration N. CRD42017076868). A total of 45 studies involving 4727 participants examined interventions for CRCI and met selection criteria. Categories of interventions included cognitive training-based intervention (N.=15), cognitive behavior therapy (CBT) (N.=4), physical activity (N.=16) and other supportive therapies (N.=10). Meta-analysis indicated beneficial overall effects for all categories of interventions: cognitive training (standardized mean difference [SMD]=0.41, 95% CI: 0.28-0.53, I2=88.87%); CBT (SMD=0.30, 95% CI: 0.14-0.46, I2=44.86%); physical activity (SMD=0.27, 95% CI: 0.20-0.35, I2=37.67%); and supportive therapies (SMD=0.27, 95% CI: 0.16-0.39, I2=64.94%). Studies used self-report cognitive outcome measures and neurocognitive testing, or a mixture. Findings suggest that effective intervention for CRCI exist, and cognitive training is consistently supported as an effective intervention; however, a high level of heterogeneity was found. CRCI research is currently dominated by breast cancer survivors, and quality research is also needed to address the broader population of cancer survivors who experience CRCI.

1828P How cancer-related cognitive impairment affects quality of life? A large survey among women with breast cancer

Cancer-related cognitive impairment (CRCI), also known as chemobrain or cancerbrain, represents cognitive impairment among cancer patients and survivors. There has been a growing interest in better understanding the perspectives and experiences of patients with CRCI, as well as its impact on their daily lives. A survey program was conducted by Kantar Health, an independent research agency, in collaboration with RoseUp, a French national cancer patient Non-Governmental Organization, to assess the health-related quality of life (QoL) of female breast cancer patients with self-reported CRCI in France.

1833P Chemobrain: Seldom studied or reported, but apparently very common

While studies have investigated a condition termed “chemobrain” or cancer-related cognitive impairment, the related data from the patients’ perspective remain scarce. A survey program was conducted by Kantar Health, an independent research agency, in collaboration with RoseUp, a French national cancer patient Non-Governmental Organization, to better-understand the phenomenon of chemobrain and to raise public awareness.

A randomised wait-list controlled trial to evaluate Emotional Freedom Techniques for self-reported cancer-related cognitive impairment in cancer survivors (EMOTICON).

BackgroundCancer-related cognitive impairment (CRCI) is a prevalent source of comprised quality of life in cancer survivors. This study evaluated the efficacy of Emotional Freedom Techniques (EFT) on self-reported CRCI (sr-CRCI).MethodsIn this prospective multicentre randomised wait-list controlled study (ClinicalTrials.gov Identifier: NCT02771028), eligible cancer survivors had completed curative treatment, were 18 years or older and screened positive for sr-CRCI with ≥ 43 on the Cognitive Failures Questionnaire (CFQ). Participants were randomised to the immediate treatment group (ITG) or wait-list control (WLC) group, based on age (< or ≥ 65 years), gender, treatment (chemotherapy or not), and centre. The ITG started to apply EFT after inclusion and performed this for 16 weeks. The WLC group could only start the application of EFT after 8 weeks of waiting. Evaluations took place at baseline (T0), 8 weeks (T1) and 16 weeks (T2). The primary outcome was the proportion of patients with sr-CRCI according to the CFQ score.FindingsBetween October 2016 and March 2020, 121 patients were recruited with CFQ ≥ 43 indicating sr-CRCI. At T1, the number of patients scoring positive on the CFQ was significantly reduced in the ITG compared to the WLC group (40.8% vs. 87.3% respectively; p<0.01). For the WLC group, a reduction in CFQ scores was observed at T2, comparable to the effect of the ITG at T1. Linear mixed model analyses indicated a statistically significant reduction in the CFQ score, distress, depressive symptoms, fatigue and also an improvement in quality of life.InterpretationThis study provides evidence for the application of EFT for sr-CRCI in cancer survivors and suggests that EFT may be useful for other symptoms in cancer survivors.

Evaluation of a new online cognitive assessment tool in breast cancer survivors with cognitive impairment: a prospective cohort study.

Currently cancer-related cognitive impairment (CRCI) is mainly assessed by means of questionnaires, which is very laborious for the patients and the supervising physician. We evaluated a new online cognitive assessment tool, the MyCognition Quotient (MyCQ, Cambridge) in breast cancer survivors with CRCI, and compared the results with a psychometric test measuring cognitive complaints, depression, and anxiety. In this prospective study, 46 adult patients between 18 and 70years old with a diagnosis of BC were studied, all complaining of disturbing cognitive impairment. They participated in a physical cognitive rehabilitation program. The patients had an online cognitive assessment (MyCQ Med by MyCognition) every 4weeks on their home computer. In addition patients were assessed in the outpatient clinic by the principal investigator at baseline, after 3 and 6months using the following validated neuro-psychological surveys: the Hospital Anxiety and Depression Scale (HADS), Beck Cognitive Insight Scale (BCIS), and Cognitive Failure Questionnaire (CFQ). MyCQ scores were correlated with the results of these surveys. Only weak correlations could be found between overall MyCQ or the MyCQ subtests with the psychometric tests (between - 0.43 and 0.458) at baseline and when combining data at time point 0, 3, and 6months. Linear mixed models showed there was a significant association between Latency Choice Reaction Time and CFQ (continuous; p = 0.026). An AUC of 0.640 and a cut-off of 481.5ms in Latency Choice Reaction Time were found to distinguish patients with CFQ below 44 to patients with CFQ above 44 (sensitivity 0.63 and specificity 0.73). In Latency Coding an AUC of 0.788 and a cut-off of 1316ms were found to distinguish non-depressive patients from patients likely to present with depressive symptoms (sensitivity 0.75 and specificity 0.76). MyCQ cannot replace the various psychometric tests. However, abnormal Latency in cognitive tests, Choice Reaction Time and Coding, seems promising to be used as a screening tool to detect specific aspects of abnormal cognitive functioning in patients with cognitive complaints and depressive symptoms.

Combined Model of Telehealth Interventions for Adults With Cancer-Related Cognitive Impairment: A Pilot Study

Abstract Date Presented 04/7/21 This study describes the feasibility of a combined telehealth intervention of computerized cognitive training together with occupation-based treatment for patients with cancer-related cognitive impairment (CRCI). The intervention was found feasible, and positive outcomes on occupational performance, cognitive functions, quality of life, and mood were revealed. This treatment can possibly add to the therapeutic landscape of CRCI, which currently impairs the life of millions worldwide. Primary Author and Speaker: Yafit Gilboa Contributing Authors: Anita Tollen, Marie Holmefur

Androgen deprivation therapy and radiation for prostate cancer—cognitive impairment, sleep, symptom burden: a prospective study

ObjectivesThis paper (1) sought to compare sleep, mood and physical symptom profiles of men with prostate cancer (PCa) who experienced subjective and objective cancer-related cognitive impairment (CRCI) during the first...

Cancer-Related Cognitive Impairment or “Chemobrain:” Emerging Assessments, Treatments, and Targets for Intervention

Cancer-Related Cognitive Impairment or “Chemobrain:” Emerging Assessments, Treatments, and Targets for Intervention

Tumour brain: Pretreatment cognitive and affective disorders caused by peripheral cancers.

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood-brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis.

Cognitive Impairment in Hodgkin Lymphoma Survivors

Introduction: Hodgkin lymphoma (HL) mostly affects young adults (median age 31y). Due to the use of efficient staging techniques and treatment methods, HL patients have a 5-year survival of 97%. Cancer-related cognitive impairment (CRCI) is a frequent complaint among HL survivors (HLS). CRCI is commonly reported following the administration of chemotherapy (“chemo-brain”). CRCI is characterized by impairment in memory, attention, executive functions and a decrease in processing speed. However, CRCI in HLS is not extensively studied. The current study aimed to assess the incidence and characteristics of CRCI in HLS.Methods: HLS who completed first-line therapy (chemo±RT) and remained in complete remission for 6 months to 5 years from the end of therapy were evaluated. Age - and education-matched healthy individuals served as controls (HC). Study participants completed self-reported questionnaires evaluating fatigue (MFI-20), depression (BDI-II), anxiety (HA), quality of life (QLQ-C30) and cognitive function (FACT-cog) and underwent a neurocognitive evaluation. The test battery included: The California verbal learning test, digit span (WAIS-III), trail making tests A+B, Stroop and Raven progressive matrices tests and 5 sub-tests from the CANTAB Computerized Battery, assessing the processing speed, memory, attention, executive functions, and intelligence domains. Test results were presented in standard scores. Since each neuropsychological test measures multiple parameters, significant representative test-parameters were chosen for each test. A domain was regarded impaired when the subject scored ≤ 1.5 SD below the expected norm, in at least one significant representative parameter belonging to a neuropsychological test.Results: The present study included 51 HLS with a median age of 28 years (range 19-48), mean education of 14.5±2.5 years and median time from end of therapy equating to 24 months (range 4-59) as well as 14 HC with a median age of 27.5 years (range 20-38) and mean education of 14.8±2.2 years.HLS reported the experience of fatigue and cognitive impairment. Severe physical fatigue was reported by to 41% of HLS and up to 25% of HC. Up to 39% HLS reported experiencing cognitive impairment versus only 17% of HC. Notably, the latter group also had significantly fewer complaints and symptoms across all scales (Table 1).In the neuropsychological evaluation, HLS scored within the impaired range on ≥1 significant representative test-parameter assessing domain: 41% on executive functions, 28% on memory and learning, 12% on attention, and 22% on processing speed. All the evaluated significant representative test-parameters are listed in (Table 2). We found that 35% of HLS were impaired on ≥1 cognitive domain and 30% - on ≥ 2 cognitive domains.Conclusions: The results of the current study evaluating CRCI in HLS are similar to those observed in other malignancies. Executive functions were the most frequently affected domain.Higher education positively correlated with superior cognitive outcomes. Given the young age of HLS and the enormous impact of CRCI on life aspects, benefit versus risk profiles of the therapeutic protocols applied in HL should be reconsidered and individually tailored. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cognitive Outcomes Among Patients with Hematological Cancer with Access to Computerized Cognitive Training: Results from a Feasibility Study

Objective: Cancer-related cognitive impairment can affect patients after treatment of hematological cancers, but evidence of the effect of cognitive training interventions in this population is limited. The objective of this study was to explore cognitive outcomes among a sample of patients with hematological cancer who were given access to an online computerized cognitive training program after treatment completion.Methods: Patients who had completed primary treatment for lymphoma, or autologous stem cell transplant for either lymphoma or multiple myeloma were recruited to test the feasibility of an 8-week computerized cognitive training intervention. All participants were assigned to receive the intervention, which was self-administered by participants at home and consisted of online brain training exercises designed to enhance information processing abilities. As part of the study, cognitive outcomes were assessed before (T1) and after (T2) the 8-week intervention, comprised of a standardized battery of neuropsychological tests, a self-report questionnaire of cognitive symptoms, and a functional assessment of medication management ability. Raw scores on neuropsychological tests were converted to T-scores based on demographically-adjusted norms (for age, sex, and education, where applicable), which were used for analysis. Composite T-scores representing performance in four cognitive domains (learning efficiency/memory, information processing speed/psychomotor efficiency, working memory, executive functioning) were computed at each time point. Wilcoxon's sum rank test was used to assess the differences in outcomes at times 1 and 2.Results: 14 patients (12 lymphoma, 2 multiple myeloma) completed cognitive measures at T1 and T2. Participants were a median 48.5 years of age (range 24-70) and a median 53.5 days from treatment completion (range 28 - 490). At baseline, 7 participants met the criteria for overall cognitive impairment based on a Global Deficit Score (GDS) ≥0.5. After 8 weeks of access to the online computerized cognitive training program, there was a statistically significant improvement in the domains of information processing speed/psychomotor efficiency (MD = 4.18, std =4.55, p=0.0042) and working memory (MD = 2.09, std = 2.74, p=0.0127). Effect sizes (d) for changes in information speed/psychomotor efficiency and working memory were 0.92 and 0.76, respectively, suggesting large effects by Cohen's d classification. There was no sufficient evidence of a difference in learning efficiency/memory, executive functioning, cognitive symptoms or medication management ability.Conclusion: Cognitive functioning in the domains of information processing speed/psychomotor efficiency and working memory were improved over the course of participation in an online self-administered computerized cognitive training program in this small sample of participants treated for hematological cancers. Post-hoc analyses to explore dose-response and factors associated with training time are forthcoming. Adequately powered studies with the inclusion of a control condition are required to determine treatment efficacy in this growing group of cancer survivors. DisclosuresKuruvilla:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; Janssen: Consultancy; Hoffman LaRoche: Consultancy; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Merck: Honoraria; Karyopharm: Research Funding; Roche: Research Funding; Celgene: Honoraria, Research Funding. Chen:Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Effect of chemotherapy on default mode network connectivity in older women with breast cancer.

Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the default mode network (DMN) in older women with breast cancer. This prospective longitudinal study enrolled women aged ≥ 60 years with stage I-III breast cancer (CTx group) and matched healthy controls (HC group). Study assessments, consisting of resting-state functional MRI (rs-fMRI) and the Picture Sequence Memory (psm) test for episodic memory from the NIH Toolbox for Cognition, were obtained at baseline and within one month after the completion of chemotherapy for the CTx group and at matched intervals for the HC group. Two-sample t-test and FDR multiple comparison were used for statistical inference. Our analysis of the CTx group (N = 19; 60-82 years of age, mean = 66.6, SD = 5.24) compared to the HC group (N = 14; 60-78 years of age, mean = 68.1, SD = 5.69) revealed weaker DMN subnetwork connectivity in the anterior brain but stronger connectivity in the posterior brain at baseline. After chemotherapy, this pattern was reversed, with stronger anterior connectivity and weaker posterior connectivity. In addition, the meta-level functional network connectivity (FNC) among theDMN subnetworks after chemotherapy was consistently weaker than the baseline FNC as seen in the couplings between anterior cingulate cortex (ACC) and retrosplenial (rSplenia) region, with ΔFNC('ACC','rSplenia')=-0.14, t value=-2.44, 95%CI=[-0.27,-0.10], pFDR<0.05). The baseline FNC matrices of DMN subnetworks were correlated with psm scores (corr = 0.58, p < 0.05). Our results support DMN alterations as a potential neuroimaging biomarker for cancer-related cognitive impairment and accelerated aging.

Phase II study of exercise and low-dose ibuprofen for cancer-related cognitive impairment (CRCI) during chemotherapy.

12016 Background: CRCI is a debilitating consequence of cancer and its treatment, including difficulties in attention, memory, and executive function. Though CRCI can develop during the course of chemotherapy, interventions targeting CRCI during chemotherapy have not been investigated. Inflammation contributes to CRCI and thus reducing inflammation may ameliorate CRCI. Using a biobehavioral approach, we investigated 2 promising interventions that reduce inflammation: exercise and low-dose ibuprofen. Methods: This is a Phase II RCT with a 2:2 factorial design. Eligible participants were patients with cancer receiving chemotherapy who self-reported cognitive difficulties. Participants were stratified by disease type (breast cancer; gastrointestinal cancer; other) and were randomized to 1 of 4 groups for 6 weeks: exercise alone (+ placebo), ibuprofen alone, exercise + ibuprofen, or placebo only. The exercise intervention, delivered by an exercise physiologist, was Exercise for Cancer Patients (EXCAP), an individually tailored, home-based prescription of walking and resistance band training. Ibuprofen/placebo was over-encapsulated for blinding; 200mg was taken 2 times per day. Participants completed 7 cognitive assessments probing attention, memory, and executive function including the Trail Making Test (TMT) and self-report (FACT-Cog) at baseline and post-intervention. ANCOVA, controlling for baseline, assessed overall Arm effects at post-intervention. Results: Of the 110 who consented to the study, 86 participants (mean age=54; 88% female; 76% breast cancer, 21% GI; 73% Stage I-III) completed baseline assessments and were randomized to one of four study arms. Ninety percent (78/86) of those completed post-intervention. Average pill compliance across all 4 groups was balanced and averaged 90.8%. Participants in the exercise and exercise + ibuprofen arms increased 2,414 and 1,073 steps respectively compared to those in placebo and ibuprofen arms increased only 464 and 412 steps respectively from pre- to post-intervention. No study-related adverse events occurred. Intent to treat ANCOVA analyses revealed a significant improvement in attention (TMT) in exercise alone compared to placebo (21.57 seconds better; p=0.003), ibuprofen alone compared to placebo (11.27 seconds better; p=0.0475), and trend for exercise + ibuprofen (7.98 seconds better; p=0.122). Those participating in both exercise arms exhibited significant improvements in the FACT-Cog Comments from Others subdomain (p&lt;0.05). Conclusions: Exercise and low-dose ibuprofen during chemotherapy improved attention in patients with cancer receiving chemotherapy. Exercise improved self-reported cognitive functioning. These results suggest possible treatment options for ameliorating CRCI during chemotherapy. Phase III trials are needed to confirm these findings. K07CA16888; DP2CA195765. Clinical trial information: NCT01238120.

Knitting to improve cognition and reduce stress in cancer survivors: A pilot study.

e24049 Background: Cancer-related cognitive impairment (CRCI), or “chemo brain,” is defined by mild cognitive changes before, during or after cancer treatment. Objective deficits on neuropsychological tests are mild, while distress about cognitive issues is often high and interventions are lacking. Skill learning, which relies upon implicit memory, promotes functional and structural neuroplasticity. This has not been explored in CRCI. We designed a standardized protocol for learning to knit over 8 weeks and recruited consecutive cancer patients with subjective cognitive concerns. Cognition and perceived stress were assessed before and after learning to knit. Methods: Sixteen cancer survivors (N=16) without any known central nervous system disease or prior knitting experience completed the study. All were female and &gt;80% were Caucasian. Mean age was 54 (SD=7) years. Mean education was 16 (SD=2) years. Neuropsychological tests were selected based on sensitivity to frontal lobe functions and memory and resistance to practice effects. Cognition and perceived stress were measured before and after the intervention, summarized, and compared using paired t-tests. P&lt;0.1 was considered statistically significant. Clinically significant cognitive change was defined by ≥1 standard deviation change between pre- and post-intervention standardized scores. Results: Baseline cognitive function was average across domains. Baseline perceived stress was moderately high. At post-testing, there were statistically significant improvements in perceived stress, cognitive flexibility, and psychomotor speed. After controlling for demographic factors, clinically significant improvements in attention and memory were seen in 38% and 25% of subjects, respectively. 69% had clinical improvement in at least one cognitive domain. Conclusions: Learning to knit produced statistically and clinically significant improvements in cognition and perceived stress in cancer survivors in 8 weeks. Most had clinical improvement in at least one cognitive domain. This skill-based pilot study suggests functional neuroplastic change is possible in selected female, college-educated cancer survivors in a short timeframe and without technology use. Future research on the impact of skill learning on cognition and stress in larger, more diverse samples of cancer survivors may yield much needed interventions for CRCI.[Table: see text]

Immune cell counts and perceived cognitive impairment before and after chemotherapy among 544 women with breast cancer.

12114 Background: In a nationwide prospective study, we found that patients with breast cancer had greater perceived cognitive impairment (PCI) before and after chemotherapy compared to controls without cancer. To gain further insight into the role that inflammation plays in cognitive function, we evaluated relationships between immune cell counts and lymphocyte:monocyte ratio with PCI at pre- and post- chemotherapy. Methods: Data were collected as part of longitudinal cohort study conducted through the National Cancer Institute Community Oncology Research Program network (NCT01382082). Self-reported PCI was scored at pre-chemotherapy (0-7 days before first chemotherapy) and post-chemotherapy (0-30 days after last chemotherapy) from the PCI sub-scale of the Functional Assessment of Cancer Therapy: Cognitive Function (possible score range 0-72). Immune cell counts were measured by complete blood count with differential at pre- and post- chemotherapy. Lymphocyte:monocyte ratio (LMR) was calculated. Separate linear regression models evaluated the association of immune cell counts and LMR with 1) pre-chemotherapy PCI and 2) post-chemotherapy PCI. Models were adjusted for age, cognitive reserve (reading score), anxiety, and depression. Results: PCI and immune cell data were available for 544 patients at pre-chemotherapy and 532 at post-chemotherapy. Subjects had a mean age of 53.1 (SD=10.8). At pre-chemotherapy, higher basophil count and higher LMR were significantly associated with worse PCI (β=5.73, SE=2.37, p&lt;0.05; β=0.047, SE=0.02, p&lt;0.05, respectively). Higher basophil count and higher LMR were also significantly associated with worse PCI at post-chemotherapy (β=5.84, SE=2.92, p&lt;0.05; β=1.01, SE=0.48, p&lt;0.05). Conclusions: These data support the hypothesis that inflammation is associated with perceived cognitive function before and after chemotherapy in adults with breast cancer. Targeting inflammatory processes may be beneficial for reducing cancer-related cognitive impairment. Funding: NCI UG1CA289961, T32CA102618, R01CA231014, DP2CA195765.

Relationship between cytokines and brain-derived neurotrophic factor (BDNF) in trajectories of cancer-related cognitive impairment

Cytokines facilitate the peripheral immune and cerebral response, through their ability to modulate the expression of brain derived neurotrophic factor (BDNF). Cytokines and BDNF are implicated in cancer-related cognitive impairment (CRCI), but their relationship has not been clearly defined for this condition. The aim of this study was to evaluate the associations of cytokines and BDNF among early stage breast cancer (ESBC) patients with different CRCI trajectories. This was a multicenter longitudinal study involving 136 ESBC patients. CRCI was assessed using the FACT-Cog (V3) questionnaire. Plasma cytokines and BDNF levels were quantified at three time points throughout chemotherapy. The associations between cytokines and BDNF were analyzed using linear mixed models, with interaction terms for CRCI status. All cytokines analyzed showed inverse associations with BDNF levels. There was a significant interaction between IL-6 and the persistent impairment trajectory, which would impact on BDNF levels (p = 0.026). The inverse associations with BDNF were more pronounced for IFN-γ, IL-1β, IL-4, IL-8, and GM-CSF in patients with persistent CRCI. The coefficient values for IL-2, IL-4, and TNF-α also indicate that there was a greater magnitude of decrease in BDNF level for every unit of cytokine increase in patients with acute and persistent CRCI, compared to patients without CRCI. The differential associations between cytokines and BDNF may be indicative of probable susceptibility to the elevation of cytokines. Further research is required to elucidate the specific associations of cytokines and BDNF, along with their contributions to acute and persistent CRCI.

Cancer-related cognitive impairment in cancer: Examining portuguese cancer survivors’ acceptability and expectations regarding cognitive telerehabilitation interventions

IntroductionCancer-related cognitive impairment (CRCI) is one of the most frequent and worrying side effects experienced by non-central nervous system (CNS) cancer survivors, generally related to cancer treatments. Considering its detrimental impact on quality of life, including work-related outcomes, it is necessary to identify effective intervention options. Cognitive rehabilitation is considered the first-line intervention to address CRCI, being effective at improving cognitive functioning. Internet-based interventions are emerging as important means of intervention in the field of cognitive rehabilitation (known as cognitive telerehabilitation), considering the potential to overcome accessibility issues and being cost-effective.ObjectivesTo assess the acceptability and expectations regarding such interventions, considering the scarce literature.MethodsA nationwide online survey was disseminated to Portuguese non-CNS cancer survivors, aged 18-65 years, who had finished active treatments, with no metastases/history of neurological or psychiatric disease/alcohol or drug abuse. Preexisting knowledge about CRCI, expectations for support to cognitive difficulties, Internet use for health and support purposes, and intervention needs and preferences in the context of cognitive telerehabilitation were examined; sociodemographic and clinical variables (e.g., age, education, employment status, cancer treatments), as well as cognitive complaints (Portuguese version of the Functional Assessment of Cancer Therapy-Cognitive, FACT-Cog), were also assessed.ResultsFindings from this study are important to help health professionals and researchers understand and identify cancer survivors’ needs regarding cognitive telerehabilitation interventions.ConclusionsThis information could be used as a support and guide for the development and delivery of these interventions for non-CNS cancer survivors.

Cognitive impairment in cancer patients and survivors—clinical presentation, pathophysiology, diagnosis and management

Cognitive impairment by neurotoxic substances, administered alone or in a multidrug regimen, affects a large number of patients treated for noncentral nervous system cancer during and after chemotherapy with variable onset, severity and duration, but sustainably affecting the patients’ individual health-related quality of life. Depending on the mechanism of action, the ability to cross the blood–brain barrier into the central nervous system and the cumulative total dose of the cytotoxic drugs results in functional and structural brain changes. This neurotoxicity leads to negative effects on neural precursor cells (neurogenesis), microglia (neuroinflammation), neurons (cortical dysfunction with altered brain networks), and astro-/oligodendroglia (white matter tract demyelination) and therefore on patients’ cognitive performance. Memory and executive functions, attention/concentration, and processing speed are the cognitive domains commonly impaired by chemotherapy. Importantly, numerous simultaneously occurring risk factors may also have distinct restrictions on cognitive function. For this reason, the term cancer-related cognitive impairment (CRCI), implicating neurotoxicity in cancer patients with simultaneous consideration of other causes on cognitive performance, should be used. The aim of this review is to provide an update of the most recent clinical and pathophysiological findings, self-reported and neuropsychological testing methods, and the current management strategies of CRCI.

Measuring Self-Reported Cancer-Related Cognitive Impairment: Recommendations From the Cancer Neuroscience Initiative Working Group.

Cancer and its treatments are associated with increased risk for cancer-related cognitive impairment (CRCI). Methods and measures used to study and assess self-reported CRCI (sr-CRCI), however, remain diverse, resulting in heterogeneity across studies. The Patient-Reported Outcomes Working Group has been formed to promote homogeneity in the methods used to study sr-CRCI. In this report, using a psychometric taxonomy, we inventory and appraise instruments used in research to measure sr-CRCI, and we consider advances in patient-reported outcome methodology. Given its psychometric properties, we recommend the Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a for measurement of sr-CRCI in cancer patients and survivors, at a minimum, to increase scientific rigor and progress in addressing CRCI.

Cognitive complications of cancer and cancer-related treatments – Novel paradigms

As advances in diagnostics and therapeutic strategies in oncology have increased the number of cancer survivors, the investigation of the mechanisms associated with long-term cognitive complications of cancer treatment has become an important topic of interest. The neurotoxic effects of chemotherapeutic agents have been described in pre-clinical and clinical research. In vitro and rodent studies have identified some underlying mechanisms contributing to chemotherapy-induced neurotoxicity and cognitive impairment for various chemotherapy drugs and other cancer treatments. However, investigation of the direct biological effects of cancer and other potential contributing factors in the pathogenesis of cancer-related cognitive impairment (CRCI) has only recently come into focus. This review will highlight evidence from pre-clinical tumor-bearing rodent models suggesting that cancer influences the cognitive and behavioral changes reported in human cancer populations through direct or indirect pathways that alter the normal neuroinflammatory responses, induce structural brain deficits, and decrease neurogenesis. We reflect on human clinical cancer research indicating that cognitive and behavioral changes precede cancer treatment in some malignancies. We also highlight implications for future areas of CRCI research based on novel findings on the interplay between cancer, chemotherapy, inflammation, tau pathology, and dysregulation of the microbiota-gut-brain axis.