The Fast Cognitive Evaluation (FaCE): a screening tool to detect cognitive impairment in patients with cancer.

Cancer-related cognitive impairment (CRCI) is one of the most concerning conditions experienced by patients living with cancer and has a major impact on their quality of life. Available cognitive assessment tools are too time consuming for day-to-day clinical setting assessments. Importantly, although shorter, screening tools such as the Montreal Cognitive Assessment or the Mini-Mental State Evaluation have demonstrated a ceiling effect in persons with cancer, and thus fail to detect subtle cognitive changes expected in patients with CRCI. This study addresses this lack of cognitive screening tools by developing a novel tool, the Fast Cognitive Evaluation (FaCE).A population of 245 patients with 11 types of cancer at different illness and treatment time-points was enrolled for the analysis. FaCE was developed using Rasch Measurement Theory, a model that establishes the conditions for a measurement tool to be considered a rating scale.FaCE shows excellent psychometric properties. The population size was large enough to test the set of items (item-reliability-index=0.96). Person-reliability (0.65) and person-separation (1.37) indexes indicate excellent internal consistency. FaCE's scale is accurate (reliable) with high discriminant ability between cognitive levels. Within the average testing time of five minutes, FaCE assesses the main cognitive domains affected in CRCI.FaCE is a rapid, reliable, and sensitive tool for detecting even minimal cognitive changes over time. This can contribute to early and appropriate interventions for better quality of life in patients with CRCI. In addition, FaCE could be used as a measurement tool in research exploring cognitive disorders in cancer survivors.

Transcranial Magnetic Stimulation for the Treatment of Chemo Brain.

This pilot feasibility study aimed to evaluate the effects of transcranial magnetic stimulation (TMS) on chemotherapy-related cognitive impairment (CRCI), and we report here on the first patient. BACKGROUND: Deleterious cognitive changes due to chemotherapy or CRCI are commonly referred to as "chemo brain". With the increasing survival of cancer patients, this poorly understood and inadequately treated condition will likewise have an increasing toll on individuals and society. Since there is no approved treatment for chemo brain, we have initiated a therapeutic trial using transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique approved in many countries for the treatment of neurologic and psychiatric conditions like migraine and depression. CASE PRESENTATION: A 58-year-old woman, diagnosed 7 years prior with left breast cancer, underwent partial mastectomy with sentinel lymph node biopsy. She then received four cycles of adjuvant chemotherapy followed by radiation therapy. Afterwards, she was on tamoxifen for 4 years and then switched to aromatase inhibitors. The patient's CRCI started during chemotherapy and severely impaired her quality of life for an additional two years. In the third year after chemotherapy, the CRCI partially cleared to stabilize to the level at the time of presentation for this trial. The patient continues to have memory difficulties and decreased concentration, which makes multi-tasking very difficult to impossible. She is reliant on memory aids at work and at home. The participant underwent 10 consecutive sessions of TMS during weekdays for 2 weeks. Stimulation was directed to the left dorsolateral prefrontal cortex. After TMS, the participant significantly improved in memory function on neuropsychological testing. While she reported no subjective differences in concentration or memory, she did report an improvement in her sleep. Functional magnetic resonance imaging of the brain before and after TMS showed increased resting-state functional connectivity between the stimulation site and several brain regions. Remarkably, after 6 years of chemo brain and remaining in the same position at work due to her inability to concentrate and multi-task, she applied for and received a promotion 5-6 months after her TMS treatments. CONCLUSIONS: This first patient in the phase 1 clinical trial testing of TMS for the treatment of "chemo brain" provided important lessons for feasibility and insights into mechanisms of potential benefit.

Exploring the experience of a cognitive rehabilitation intervention for cancer-related cognitive change in people living with cancer: An interpretative phenomenological analysis.

OBJECTIVES: Some cancer patients experience cancer-related cognitive change (CRCC). Cognitive rehabilitation interventions (CRIs) have recently been developed to help mitigate the impact of CRCC, which, untreated, can impact resumption of daily life post-cancer treatment. The experience of participants is important to understand but largely absent within research literature. This study aimed to explore how those with CRCC experience the phenomenon following completion of a CRI. METHODS: This study comprised a qualitative phenomenological approach. This involved conducting in-depth, semi-structured interviews with 6 self-referred participants from one CRI. Participants were invited to discuss their experience of CRCC and what the CRI therefore meant to them. Interviews were analyzed using interpretative phenomenological analysis. RESULTS: Analysis of the findings revealed 4 key themes. (1) "Experiencing and addressing isolation" comprises reflections on posttreatment perceived abandonment and consequent feelings of belonging through CRI participation. (2) "Identity" explores participants' reflections around perceived loss-of-self and feelings of empowerment from the intervention. (3) "Cognitive and physical balance" comprises the planning and choices participants make, supported by both their own and CRI coping strategies as they seek acceptance of cognitive change. (4) "Course reflections" explore reflections on intervention structure, format, and delivery, focusing on 2 subthemes of accessibility, flexibility and inclusivity, and communication. All participants reflected positively on their experience. SIGNIFICANCE OF RESULTS: Results support further dissemination among health professionals and implementation of this CRI to better support self-reported CRCC concerns within this population. Future qualitative research should explore the long-term impact of CRI interventions.

The effect of doxorubicin or cyclophosphamide treatment on auditory brainstem response in mice.

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. Several underlying mechanisms have been proposed; however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. There is evidence that oligodendrocytes and white matter tracts within the CNS may be particularly vulnerable to chemotherapy-related damage and dysfunction. Auditory brainstem responses (ABRs) have been used to detect and measure functional integrity of myelin in a variety of animal models of autoimmune disorders and demyelinating diseases. Limited evidence suggests that increases in interpeak latencies, associated with disrupted impulse conduction, can be detected in ABRs following 5-fluorouracil administration in mice. It is unknown if similar functional disruptions can be detected following treatment with other chemotherapeutic compounds and the extent to which alterations in ABR signals represent robust and long-lasting impairments associated with chemotherapy-related cognitive impairment. Thus, C57BL/6 J mice were treated every 3rd day for a total of 3 injections with low or high dose cyclophosphamide, or doxorubicin. ABRs of mice were assessed on days 1, 7, 14, 56 and 6 months following completion of chemotherapy administration. There were timing and amplitude differences in the ABRs of the doxorubicin and the high dose cyclophosphamide groups relative to the control animals. However, despite significant toxic effects as assessed by weight loss, the changes in the ABR were transient.

Diet quality indices and changes in cognition during chemotherapy.

PURPOSE: No evidence-based prevention strategies currently exist for cancer-related cognitive decline (CRCD). Although patients are often advised to engage in healthy lifestyle activities (e.g., nutritious diet), little is known about the impact of diet on preventing CRCD. This secondary analysis evaluated the association of pre-treatment diet quality indices on change in self-reported cognition during chemotherapy. METHODS: Study participants (n = 96) completed the Block Brief Food Frequency Questionnaire (FFQ) before receiving their first infusion and the PROMIS cognitive function and cognitive abilities questionnaires before infusion and again 5 days later (i.e., when symptoms were expected to be their worst). Diet quality indices included the Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet (aMED), and a low carbohydrate diet index and their components. Descriptive statistics were generated for demographic and clinical variables and diet indices. Residualized change models were computed to examine whether diet was associated with change in cognitive function and cognitive abilities, controlling for age, sex, cancer type, treatment type, depression, and fatigue. RESULTS: Study participants had a mean age of 59 ± 10.8 years and 69% were female. Although total diet index scores did not predict change in cognitive function or cognitive abilities, higher pre-treatment ratio of aMED monounsaturated/saturated fat was associated with less decline in cognitive function and cognitive abilities at 5-day post-infusion (P ≤ .001). CONCLUSIONS: Higher pre-treatment ratio of monounsaturated/saturated fat intake was associated with less CRCD early in chemotherapy. Results suggest greater monounsaturated fat and less saturated fat intake could be protective against CRCD during chemotherapy.

Protective effect of Juglanin against doxorubicin-induced cognitive impairment in rats: Effect on oxidative, inflammatory and apoptotic machineries.

Doxorubicin (DOX) is an effective anticancer drug, however, side effects such as cognitive impairment and cardiotoxicity have limited its clinical use. Juglanin (JUG) is a flavonoid with excellent antioxidant, anti-inflammatory, neuroprotective and anticancer properties. This study investigated the protective effects of JUG against DOX-induced cognitive decline, oxidative stress and inflammatory response in rats. The rats were orally administrated with JUG or JUG in combination with DOX. After treatment, the animals were subjected to series of behavioral test including Morris water maze, Y-maze and forced swimming tests. After the study, the rats were sacrificed and the level of acetylcholinesterase (AchE), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), caspase 3 and Nuclear factor kappa B (NF-кB) were assayed in the brain. Histopathological analysis was also performed on the brain of the rats. JUG significantly protected against DOX-induced cognitive impairment and depressive behaviors. In addition, JUG attenuated altered brain histopathological architecture, reduced oxido-inflammatory responses, acetylcholinesterase and caspase 3 activity in the brain of the treated rats. Collectively, the results suggested that JUG offered neuroprotection against DOX induced Chemobrain via ameliorating oxidative stress and inflammation.

Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial.

BACKGROUND: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer. METHODS: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline. DISCUSSION: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017.

Predicting chemo-brain in breast cancer survivors using multiple MRI features and machine-learning.

PURPOSE: Breast cancer (BC) is the most common cancer in women worldwide. There exist various advanced chemotherapy drugs for BC; however, chemotherapy drugs may result in brain damage during treatment. When a patient's brain is changed in response to chemo drugs, it is termed chemo-brain. In this study, we aimed to construct machine-learning models to detect the subtle alternations of the brain in postchemotherapy BC patients. METHODS: Nineteen BC patients undergoing chemotherapy and 20 healthy controls (HCs) were recruited for this study. Both groups underwent resting-state functional MRI and generalized q-sampling imaging (GQI). RESULTS: Logistic regression (LR) with GQI indices in standardized voxel-wise analysis, LR with mean regional homogeneity in regional summation analysis, decision tree classifier (CART) with generalized fractional anisotropy in voxel-wise analysis, and XGBoost (XGB) with normalized quantitative anisotropy had formidable performances in classifying subjects into a chemo-brain group or an HC group. Classifying the brain MRIs of HC and postchemotherapy patients by conducting leave-one-out cross-validation resulted in the highest accuracy of 84%, which was attained by LR, CART, and XGB with multiple feature sets. CONCLUSIONS: In our study, we constructed the machine-learning models that were able to identify chemo-brains from normal brains. We are hopeful that these results will be helpful in clinically tracking chemo-brains in the future.

Testing a novel account of the dissociation between self-reported memory problems and memory performance in chemotherapy-treated breast cancer survivors.

BACKGROUND: A puzzling observation pertaining to the impact of breast cancer on memory is the frequently reported dissociation between breast cancer survivors' self-reported memory problems and memory performance. We evaluated the hypothesis that the dissociation is related to the fact that the objective memory measures previously used assessed retrospective memory (RM) and did not tap prospective memory (PM), a domain about which survivors are complaining. METHODS: In a case-healthy-control (N = 80) cross-sectional study, the Memory for Intention Screening Test was used to assess PM and the Wechsler Logical Memory Test was used to evaluate RM. Self-reported problems were assessed with the Prospective and Retrospective Memory Questionnaire. Measures of depression (Center for Epidemiologic Studies Depression Scale) and fatigue (Functional Assessment of Cancer Therapy: Fatigue) were also administered. RESULTS: Both groups reported more PM than RM problems (P < .001). Survivors reported more fatigue and depression symptoms and more memory problems than controls (all P < .001). Importantly, the group difference in self-reported problems was no longer observed after adjusting for depression and fatigue. Survivors performed worse than controls on both PM and RM tasks. In neither group, however, were associations between self-reported RM and PM problems and RM and PM objective performance observed. CONCLUSIONS: Breast cancer survivors exhibit PM and RM deficits, which do not correlate with self-reported memory problems. Although unrelated to performance, memory complaints should not be dismissed, as they are closely associated with depression and fatigue and reveal an important facet of the cancer experience.

A brief psychoeducational intervention improves memory contentment in breast cancer survivors with cognitive concerns: results of a single-arm prospective study.

PURPOSE: One in three breast cancer survivors experiences persistent cognitive changes that can negatively impact daily functioning and quality of life. In our cancer center, the largest tertiary cancer center in Canada, patients with self-reported cancer-related cognitive dysfunction (CRCD) are offered psychoeducation intended to reduce distress about CRCD symptoms and improve everyday cognitive performance, but evidence regarding this intervention's impact is lacking. Here, we assess whether a 1-hour (h), individual psychoeducational intervention designed to promote self-management of CRCD symptoms can improve attitudes and coping with memory-related difficulties in women with breast cancer. METHODS: Breast cancer survivors with self-reported CRCD (N = 100) were assessed immediately before, immediately after, and 6 weeks following the intervention. Participants' memory contentment, knowledge of CRCD, symptom distress, and self-efficacy to cope with symptoms were measured. RESULTS: Participants showed improvements in memory contentment immediately after the intervention (Cohen's d effect size and 95% CI = 0.87 [0.58, 1.16]) and 6 weeks later (d = 0.77 [0.48, 1.05]). Significant improvements in secondary study outcomes, including knowledge of CRCD (d = 1.32 [1.01, 1.63]), symptom distress (d = - 0.82 [- 1.11, - 0.53]), and self-efficacy to cope with cognitive symptoms (d = 1.45 [1.14, 1.76]), were also observed. CONCLUSIONS: A single, 1-hour psychoeducational intervention can achieve lasting and improved adjustment to memory symptoms in breast cancer survivors with self-reported CRCD. Further investigation using a randomized controlled study design is warranted. Comparisons with previously reported psychoeducational interventions for CRCD are made, and next steps for this research are discussed.

Web-based cognitive training for breast cancer survivors with cognitive complaints-a randomized controlled trial.

BACKGROUND: Cognitive complaints are common amongst breast cancer survivors, and no standard treatment exists. The present study evaluates whether web-based cognitive training can alleviate subjectively reported and objectively assessed cognitive complaints in a sample of breast cancer survivors. The primary and secondary outcomes were an objective measure of working memory and a measure of perceived cognitive functioning. Additional outcomes were neuropsychological tests of memory, executive function, working memory and questionnaire-based assessment of anxiety, depression and somatization. METHODS: A total of 157 female breast cancer survivors were recruited from an existing cohort and through announcements in open access cancer-related Internet fora and randomly allocated to either web-based cognitive training (eCogT) with telephone support (n = 94) or a waitlist control (WLC) condition (n = 63). eCogT encompassed 30 training sessions over 6 weeks. Neuropsychological assessments were undertaken over the telephone, and questionnaire data was collected online. Data was collected at baseline, post-intervention and at 5-month follow-up. RESULTS: Mixed linear models revealed no statistically significant change in primary or secondary outcome at follow-up in either group. Statistically significant improvements (p 0.040-0.043) were found in the eCogT group for verbal learning and on a working memory test. CONCLUSIONS: Web-based cognitive training did not result in improvements of the primary or secondary outcome. Improved performance was observed on verbal learning and working memory. These effects were observed at 5-month follow-up, indicating long-term effects of training. The intervention may be applied in a clinical setting at low cost and without risk of adverse effects.© 2016 The Authors Psycho-Oncology Published by John Wiley & Sons Ltd.

Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits.

Over the past several decades, research in both humans and animals has established the existence of persistent cognitive deficits resulting from exposure to chemotherapeutic agents. Nevertheless, there has been very little research addressing the treatment of chemotherapy-induced cognitive deficits and there is currently no approved treatment for this condition, often referred to as 'chemo-brain.' Several drugs that enhance cholinergic function and/or increase nicotinic acetylcholine receptor (nAChR) activity have been demonstrated to improve cognitive performance and/or reverse cognitive deficits in animals, findings that have led to the use of these compounds to treat the cognitive deficits present in a variety of disorders including attention deficit disorder, Alzheimer's disease, Parkinson's disease and schizophrenia. Although nAChR agonists have not been assessed for their efficacy in treating chemotherapy-induced cognitive deficits, these drugs have been shown to produce measureable increases in performance on several behavioral tasks known to be disrupted by exposure to chemotherapeutic agents. While the processes underlying chemotherapy-induced cognitive deficits may differ from those underlying other disorders, there appears to be a broad spectrum of application for the use of nAChR agonists to improve cognitive function. Therefore, studies examining the use of these drugs in the treatment of chemotherapy-induced cognitive deficits should be conducted as they may be of benefit for the treatment of 'chemo-brain.'

Effects of Cannabidiol (CBD) on Doxorubicin-Induced Anxiety and Depression-like Behaviors and mRNA Expression of Inflammatory Markers in Rats.

Background: Post-treatment side effects of chemotherapy can include cognitive deficits commonly known as Chemo-brain. The treatment of patients with Doxorubicin (DOX), one of the most widely used chemotherapeutic drugs in the treatment of cancer, can induce depression, anxiety, and impaired cognitive function. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa that has been identified as a possible therapeutic agent against many neurodegenerative disorders, including traumatic brain injury, spinal cord injury, Tau-protein-induced neurodegeneration, and neuropathic pain. Therefore, this study aimed to assess whether oral CBD administration could reduce DOX-induced anxiety and depression-like behaviors and alter the expression of mRNA associated with neuroinflammation. Methods: Female Long Evans Hooded rats received intraperitoneal injections of DOX (6 mg/kg) or the vehicle (0.9% saline) once a week for four weeks, followed by oral administration of CBD (10 mg/kg) three times a week for the same period. Results: CBD was significantly protective against DOX-induced anxiety and depression-like behaviors, as measured by several behavioral tests. Furthermore, CBD improved DOX-induced alterations in the gene expression of biomarkers of neuroinflammation in the hippocampus and prefrontal cortex. Conclusions: This provides insights into future studies on possible mechanisms by which DOX-induced cognitive dysfunction could be alleviated by CBD.

Melatonin mitigates doxorubicin induced chemo brain in a rat model in a NRF2/p53-SIRT1 dependent pathway.

Cancer is a critical health problem, and chemotherapy administration is mandatory for its eradication. However, chemotherapy like doxorubicin (Dox) has serious side-effects including cognitive impairment or chemo brain. Melatonin is a neuroprotective agent that has antioxidant, and anti-inflammatory effects. We aimed to explore melatonin's effect on Dox-induced chemo brain to discover new mechanisms associated with Dox-induced neurotoxicity and try to prevent its occurrence. Thirty-two male albino rats had been equally divided into four groups; control, melatonin-administrated, Dox-induced chemo brain, and melatonin + Dox treated. On the 9th day, brain had been excised after scarification and had been assessed for reactive oxygen species measurement, histopathological analysis, immunohistochemical, gene and protein expressions for the nuclear factor erythroid 2-related factor 2 (Nrf2), p53 and Silent information regulator 2 homolog 1 (SIRT1). Our results show that melatonin coadministration diminished Dox induced hippocampal and prefrontal cortex (PFC) cellular degeneration. It alleviated Nitric Oxide (NO) level and reversed the decline of antioxidant enzyme activities. It also upregulated Nrf2, SIRT1 and downregulated p53 gene expression in rats receiving Dox. Moreover, melatonin elevated the protein expression level of Nrf2, SIRT1 and reduced p53 corresponding to immunohistochemical results. The data suggested that melatonin can mitigate Dox-induced neurotoxicity by aggravating the endogenous antioxidants and inducing neurogenesis through activation of Nrf2/p53-SIRT1signaling pathway in adult rats' PFC. These effects were associated with Nrf2, SIRT1 activation and p53 inhibition. This could be guidance to add melatonin as an adjuvant supplement to Dox regimens to limit its adverse effect on the brain function.

Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

WHAT IS KNOWN AND OBJECTIVE: Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. COMMENT: A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. WHAT IS NEW AND CONCLUSION: Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation.

Effectiveness of a Computerized Home-Based Cognitive Stimulation Program for Treating Cancer-Related Cognitive Impairment.

Cancer patients assert that after chemotherapy their cognitive abilities have deteriorated. Cognitive stimulation is the clinical treatment of choice for reversing cognitive decline. The current study describes a computerized home-based cognitive stimulation program in patients who survived breast cancer. It aims to assess safety and effectiveness of cognitive stimulation in the oncology population. A series of 45-min training sessions was completed by the participants. A thorough assessment was performed both before and after the intervention. The mini-Mental Adjustment to Cancer Scale, the Cognitive Assessment for Chemo Fog Research, and the Functionality Assessment Instrument in Cancer Treatment-Cognitive Function served as the main assessment tools. The State-Trait Anxiety Inventory, Beck Depression Inventory, Brief Fatigue Inventory, and Measuring Quality of Life-The World Health Organization data were gathered as secondary outcomes. Home-based cognitive stimulation demonstrated beneficial effects in the oncology population, with no side effects being reported. Cognitive, physical, and emotional improvements were observed, along with decreased interference in daily life activities and a better overall quality of life.

Vildagliptin restores cognitive function and mitigates hippocampal neuronal apoptosis in cisplatin-induced chemo-brain: Imperative roles of AMPK/Akt/CREB/ BDNF signaling cascades.

Cisplatin (CP) is a broad-spectrum antineoplastic agent used to treat many human cancers. Nonetheless, most patients receiving CP suffer from cognitive deficits, a phenomenon termed "chemo-brain". Recently, vildagliptin (Vilda), a DPP-4 inhibitor, has demonstrated promising neuroprotective properties against various neurological diseases. Therefore, the present study aims to investigate the potential neuroprotective properties of Vilda against CP-induced neurotoxicity and elucidate the underlying molecular mechanisms. Chemo-brain was induced in Sprague-Dawley rats by i.p injection of CP at a dose of 5 mg/kg once weekly for four weeks. Vilda was administered daily at a dose (10 mg/kg; P.O) for four weeks. The results revealed that Vilda restored the cognitive function impaired by CP, as assessed by the Morris water maze, Y-maze, and passive avoidance tests. Moreover, Vilda alleviated the CP-induced neurodegeneration, as shown by toluidine blue staining, besides markedly reduced amyloid plaque deposition, as evidenced by Congo red staining. Notably, Vilda boosted cholinergic neurotransmission through the downregulation of the acetylcholinesterase enzyme. In addition, the neuroprotective mechanisms of Vilda include diminishing oxidative stress by reducing MDA levels while raising GSH levels and SOD activity, repressing neuronal apoptosis as shown by elevated Bcl-2 levels together with diminished Bax and caspase-3 expressions, inhibiting neuroinflammation as shown by decreased GFAP expression, and finally boosting hippocampal neurogenesis and survival by upregulating expressions of BDNF and PCNA. These effects were mainly mediated by activating AMPK/Akt/CREB signaling cascades. In summary, Vilda can be considered a promising candidate for guarding against CP-induced chemo-brain and neurodegeneration, thus improving the quality of life of cancer patients.

A scoping review of cognitive assessment tools and domains for chemotherapy-induced cognitive impairments in cancer survivors.

Backgrounds: Cancer survivors suffer from specific symptoms known as chemotherapy-induced cognitive impairments (CICIs). CICIs are difficult to capture with existing assessments such as the brief screening test for dementia. Although recommended neuropsychological tests (NPTs) exist, international consensus and shared cognitive domains of assessment tools are unknown. The aim of this scoping review was as follows: (1) to identify studies that assess CICIs in cancer survivors; (2) to identify shared cognitive assessment tools and domains by mapping the domains reported in studies using the International Classification of Functioning, Disability and Health (ICF) framework. Methods: The study followed the recommendations made by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched the following three databases through October 2021: PubMed, CINAHL, and Web of Science. Prospective longitudinal or cross-sectional studies were selected to determine CICI-specific assessment tools for adult cancer survivors. Results: Sixty-four prospective studies (36 longitudinal studies and 28 cross-sectional studies) were included after checking for eligibility. The NPTs were divided into seven main cognitive domains. The specific mental functions were often used in the order of memory, attention, higher-level cognitive functions, and psychomotor functions. Perceptual functions were used less frequently. In some ICF domains, shared NPTs were not clearly identified. In some different domains, the same NPTs were used, such as the trail making test and the verbal fluency test. When the association between the publishing year and the amount of NPT use was examined, it was found that the amount of tool use tended to decline over the publication years. The Functional Assessment of Cancer Therapy-Cognitive function (FACT-Cog) was a shared consensus tool among the patient-reported outcomes (PROs). Conclusion: Chemotherapy-induced cognitive impairments are currently gaining interest. Shared ICF domains such as memory and attention were identified for NPTs. There was a gap between the publicly recommended tools and the tools actually used in the studies. For PROs, a clearly shared tool, FACT-Cog, was identified. Mapping the domains reported in studies using the ICF can help in the process of reviewing consensus on which NPTs may be used to target cognitive domains. Systematic review registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053710, identifier UMIN000047104.

Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF.

The cognitive and behavioral decline observed in cancer survivors who underwent doxorubicin (DOX)-based treatment raises the need for therapeutic interventions to counteract these complications. Galangin (GAL) is a flavonoid-based phytochemical with pronounced protective effects in various neurological disorders. However, its impact on DOX-provoked neurotoxicity has not been clarified. Hence, the current investigation aimed to explore the ability of GAL to ameliorate DOX-provoked chemo-brain in rats. DOX (2 mg/kg, once/week, i.p.) and GAL (50 mg/kg, 5 times/week., via gavage) were administered for four successive weeks. The MWM and EPM tests were used to evaluate memory disruption and anxiety-like behavior, respectively. Meanwhile, targeted biochemical markers and molecular signals were examined by the aid of ELISA, Western blotting, and immune-histochemistry. In contrast to DOX-impaired rats, GAL effectively preserved hippocampal neurons, improved cognitive/behavioral functions, and enhanced the expression of the cell repair/growth index, BDNF. The antioxidant feature of GAL was confirmed by the amelioration of MDA, NO and NOX-1, along with restoring the Nrf-2/HO-1/GSH cue. In addition, GAL displayed marked anti-inflammatory properties as verified by the suppression of the HMGB1/TLR4 nexus and p-NF-κB p65 to inhibit TNF-α, IL-6, IL-1ß, and iNOS. This inhibitory impact extended to entail astrocyte activation, as evidenced by the diminution of GFAP. These beneficial effects were associated with a notable reduction in p-p38MAPK, p-JNK1/2, and p-ERK1/2, as well as the necroptosis cascade p-RIPK1/p-RIPK3/p-MLKL. Together, these pleiotropic protective impacts advocate the concurrent use of GAL as an adjuvant agent for managing DOX-driven neurodegeneration and cognitive/behavioral deficits. DATA AVAILABILITY: The authors confirm that all relevant data are included in the supplementary materials.

Diagnostic Accuracy of Machine-Learning Models on Predicting Chemo-Brain in Breast Cancer Survivors Previously Treated with Chemotherapy: A Meta-Analysis.

We performed a meta-analysis of chemo-brain diagnostic, pooling sensitivities, and specificities in order to assess the accuracy of a machine-learning (ML) algorithm in breast cancer survivors previously treated with chemotherapy. We searched PubMed, Web of Science, and Scopus for eligible articles before 30 September 2022. We identified three eligible studies from which we extracted seven ML algorithms. For our data, the χ2 tests demonstrated the homogeneity of the sensitivity's models (χ2 = 7.6987, df = 6, p-value = 0.261) and the specificities of the ML models (χ2 = 3.0151, df = 6, p-value = 0.807). The pooled area under the curve (AUC) for the overall ML models in this study was 0.914 (95%CI: 0.891-0.939) and partial AUC (restricted to observed false positive rates and normalized) was 0.844 (95%CI: 0.80-0.889). Additionally, the pooled sensitivity and pooled specificity values were 0.81 (95% CI: 0.75-0.86) and 0.82 (95% CI: 0.76-0.86), respectively. From all included ML models, support vector machine demonstrated the best test performance. ML models represent a promising, reliable modality for chemo-brain prediction in breast cancer survivors previously treated with chemotherapy, demonstrating high accuracy.