People diagnosed with cancer who undergo chemotherapy commonly encounter cognitive changes, particularly in executive functions (EFs). EFs support goal-directed behaviours, with EF deficits implicated in various neurocognitive impairments. We conducted five meta-analyses of the rodent models to investigate the impact of chemotherapy across five EF domains. A systematic search across PubMed, Web of Science, Scopus, and PsycINFO yielded 56 eligible papers. Our findings supported the clinical literature suggesting the selective impact of chemotherapy on different EF domains. Specifically, chemotherapy-treated animals performed significantly more poorly than controls in tasks assessing working memory, behavioural flexibility, and problem-solving, with no significant group differences in inhibition or attention. Subgroup analyses revealed that alkylating agents, antitumor antibiotics, and combination therapies were strongly associated with working memory deficits, whereas mitotic inhibitors were not. Rodent species, strain, age, sex, number of treatments, and time of behavioural assessment since the end of treatment did not moderate the drug effect on any assessed EF domains. To increase the generalisability and translational validity of the results, the overall reporting quality of animal studies needs to be improved with more details on randomisation, blinding, sample sizes, and criteria for animal exclusions.

Cancer-related cognitive impairment (CRCI) has been associated with altered brain activation after chemotherapy in areas related to working memory. Hence, improving working memory capacity and associated brain activation might aid in the recovery of CRCI. In this study, we investigated the potential of a mindfulness-based intervention (MBI) to impact working memory-related brain activation.

Female breast cancer survivors reporting cognitive complaints (N=117) were randomized into a mindfulness (n=43; MBI), physical training (n=36; PT), or waitlist control condition (n=38; WL). Participants completed MRI scans before the intervention, immediately after, and three months post-intervention. Task-based functional MRI was used to measure differences between groups over time in working memory-related brain activation while performing a visual-verbal n-back task.

Data of 83 participants (32/26/25 MBI/PT/WL) was included. Compared to the waitlist group, MBI participants showed reduced task-related activation in the right middle frontal and angular gyrus and increased activation in the right dorsal posterior cingulate cortex over time. Compared to the physical training group, MBI participants showed reduced brain activation in the bilateral superior parietal lobule and right dorsal anterior cingulate cortex over time. No differences between physical training and no intervention were identified.

This study showed that an 8-week mindfulness-based intervention can significantly alter brain activation across brain regions involved in working memory, attentional control, and emotion processing during performance of a working memory task. This might aid in the recovery of CRCI.

Mindfulness might alter brain activation patterns while performing a working memory task, which might ultimately aid in restoring higher order cognitive functions.

Cancer-related cognitive impairment (CRCI) is a common side effect of cancer and its treatments. Cancer chemotherapy has been associated with hippocampal dysfunction and memory impairment. We investigated the effects of one chemotherapy agent, doxorubicin, on the transcription factor Ascl1 and proliferation of stem cells in the brain. We used an inducible mouse model designed to express TdTomato in Ascl1-lineage cells. Five to six-month-old Ascl1-CreERT2:ROSA mice were treated peripherally with a single dose of either doxorubicin (10 mg/kg) or DMSO control (n = 9 per group, n = 4-5 per sex). We analyzed brains of mice that had been exposed to doxorubicin for 2 weeks and had induced Ascl1 expression after the first week. We used immunostaining of neurogenesis stage specific markers to evaluate the doxorubicin effects on neuronal differentiation in the dentate gyrus of the hippocampus. Overall, doxorubicin significantly increased Ascl1 expression by 81% at this time point. As measured by Ascl1 double stains with Sox2, GFAP, and NeuroD1, doxorubicin-treated mice experienced an increase in Ascl1-mediated neural proliferation compared to control. A similar significant increase in the number of Ascl1-expressing cells (by 146%) after doxorubicin treatment was observed in the gray matter of the cerebral cortex. Thus, rather than leading to the loss of developing neurons, we found that a single dose of doxorubicin increased their appearance and progression, suggesting that hippocampal losses from chemotherapies may require greater and more sustained damage.

Cancer and kidney diseases (KD) intersect in many ways resulting in worse outcomes. Both conditions are correlated with cognitive impairment, which can be exacerbated in cancer patients by known effects of many antineoplastic drugs on cognition, leading to a phenomenon known as chemotherapy-related cognitive impairment (CRCI). This manifests as poor attention span, disturbed short-term memory, and general mental sluggishness. This literature review explores CRCI and investigates the potential impact of KD on this phenomenon. Additionally, we highlight the shared pathogenetic mechanisms (including neurotoxicity, neuroinflammation, oxidative stress, vascular disease, electrolyte, and acid-base imbalances), clinical presentation and imaging findings between cognitive impairment in KD and CRCI. The disruption of the blood-brain barrier might be a key mechanism for increased brain permeability to anticancer drugs in nephropathic patients with cancer. Based on existing knowledge, we found a potential for heightened neurotoxicity of antineoplastic drugs and a synergistic potentiation of cognitive impairment in cancer patients with KD. However, further translational research is urgently required to validate this hypothesis.

One of the most debilitating drawbacks of cisplatin chemotherapy is neurotoxicity which elicits memory impairment and cognitive dysfunction (chemobrain). This is primarily triggered by oxidative stress and inflammation. Captopril, an angiotensin-converting enzyme inhibitor, has been reported as a neuroprotective agent owing to its antioxidant and anti-inflammatory effects.

We examined the possible neuroprotective effect of captopril against cisplatin-induced neurological and behavioral abnormalities in rats.

Chemobrain was induced in rats by cisplatin (5 mg/kg, i.p.) on the 7th and 14th days of the study while captopril was administered orally (25 mg/kg) daily for three weeks. The effects of captopril were assessed by performing behavioral tests, histological examination, and evaluation of oxidative stress and inflammatory markers.

Cisplatin caused learning/memory dysfunction assessed by passive avoidance and Y-maze tests, decline in locomotion, and rotarod motor balance loss which were further verified by neurodegeneration observed in histological examination. Also, cisplatin aggravated oxidative stress by elevating lipid peroxidation (MDA) levels and diminishing catalase activity. Moreover, cisplatin upregulated the neuroinflammatory markers (TNF, IL-6, GFAP, and NF-κB). Captopril successfully ameliorated cisplatin damage on the levels of neurobehavioral and histopathological changes. Mechanistically, captopril significantly diminished MDA production and preserved catalase antioxidant activity. Captopril also counteracted neuroinflammation through inhibiting NF-κB and its downstream proinflammatory cytokines besides repressing astrocyte activity by reducing GFAP expression.

Our findings revealed that captopril could abrogate cisplatin neurotoxicity via reducing oxidative stress and neuroinflammation thus enhancing cognitive and behavioral performance. This could suggest the repurposing of captopril as a neuroprotective agent, especially in hypertensive cancer patients receiving cisplatin.

Golden berries (Physalis peruviana) are esteemed for their healing properties and widespread use in traditional medicine, particularly for their neuroprotective benefits.

This work aims to evaluate the neuroprotective effect of golden berry total leaf extract cultivated in Egypt (TLE) against cyclophosphamide (CP)-induced neurotoxicity and to identify the chemical composition of different organs of P. peruviana from both Egypt and USA.

Metabolite profiling of TLE was conducted using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). In the animal model experiment, CP (100 mg/kg, i.p.) was administered once weekly for four weeks to induce neurocognitive dysfunction. Concurrently, TLE (500 mg/kg, orally) was administered twice weekly throughout the four weeks to evaluate its effectiveness in alleviating CP-induced neuronal deficits. Behavioral assessments, Morris water maze and passive avoidance tests, were conducted, followed by, histological evaluations of brain tissue samples. Additionally, biochemical analyses were performed on hippocampal tissue samples, examining the following markers, acetylcholinesterase activity (AChE), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) activity, nuclear factor kappa B (p-NF-κB p65) (Ser536), Interleukin 1β (IL-1β), Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), B-cell lymphoma 2 (Bcl-2), and Bax (Bcl-2-associated X) levels.

TLE significantly preserved hippocampal neurons and improved cognitive performance in behavioral tests. TLE achieved these beneficial effects by suppressing AChE activity, diminishing the oxidative stress and restoring redox balance via inhibiting p-NFκB/IL-1β,/TNFα/IL-6 cascades. Leaf extract revealed the highest total phenolic content (TPC) (2.7 ± 6.41 mg GAE/g extract) and total flavonoid content (TFC) (0.37 ± 1.19 mg QE/g) and the strongest antioxidant effects in Ferric Reducing Antioxidant Power (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays with IC50 values of 21.13 ± 1.48 and 18.19 ± 1.29 μg/mL, respectively. UHPLC-QTOF-MS/MS analysis resulted in the tentative identification of 20 metabolites including phenolic acids, flavonoids, hydroxycinnamic acid amides, and alkyl resorcinols.

Findings verify for the first time the neuroprotective potential of golden berry leaf, currently discarded as agricultural waste, and highlight its multifaceted mechanism of neuroprotection in CP-induced neurotoxicity, suggesting its suitability as a promising therapeutic agent for neurotoxicity management.

The aim of this study is to investigate the neuroprotective effect of roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor on cognitive impairment induced by doxorubicin (DOX)/cyclophosphamide (CP) combination therapy and to elucidate its modulatory effect on the pyroptosis pathway.

Rats were allocated into five groups: a control group, a DOX/CP-intoxicated group, two groups receiving DOX/CP plus low-dose (0.5 mg/kg/day) or high-dose (1 mg/kg/day) roflumilast, and a roflumilast-only group. Behavioral assessments and brain tissue analyses were conducted, including histopathological staining and the measurement of inflammatory and oxidative stress markers.

DOX/CP treatment resulted in cognitive impairment, abnormal brain histology. It significantly elevated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and malondialdehyde (MDA). Concurrently, superoxide dismutase (SOD) activity was reduced. Pyroptosis-associated markers, including nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin-D (GSDMD), and interleukin-18 (IL-18) were upregulated. Apoptotic marker caspase-3 also exhibited increased expression. Conversely, administration of roflumilast (1 mg/kg/day) for four weeks ameliorated these pathological changes. Roflumilast improved cognitive function, reduced oxidative stress, and modulated inflammatory signaling. Additionally, it suppressed pyroptotic and apoptotic pathways within hippocampal tissue.

These results suggest that roflumilast exerts neuroprotective effects against chemotherapy-induced cognitive dysfunction and neurodegeneration through inhibition of the NLRP3/ASC/caspase-1/GSDMD pyroptosis pathway.

The rise in global cancer burden, notably breast cancer, emphasizes the need to address chemotherapy-induced cognitive impairment, also known as chemobrain. Although chemotherapy drugs are effective against cancer, they can trigger cognitive deficits. This has triggered the exploration of preventive strategies and novel therapeutic approaches. Nanomedicine is evolving as a promising tool to be used for the mitigation of chemobrain by overcoming the blood-brain barrier (BBB) with innovative drug delivery systems. Polymer and lipid-based nanoparticles enable targeted drug release, enhancing therapeutic effectiveness. Utilizing the intranasal route of administration may facilitate drug delivery to the central nervous system (CNS) by circumventing first-pass metabolism. Therefore, knowledge of nasal anatomy is critical for optimizing drug delivery via various pathways. Despite challenges, nanoformulations exhibit the potential in enhancing brain drug delivery. Continuous research into formulation techniques and chemobrain mechanisms is vital for developing effective treatments. The intranasal administration of nanoformulations holds promise for improving therapeutic outcomes in chemobrain management. This review offers insights into potential future research directions, such as exploring novel drug combinations, investigating alternative delivery routes, or integrating emerging technologies to enhance the efficacy and safety of nanoformulations for chemobrain management.

Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms that may persist years after early-stage breast cancer, affecting quality of life. We aimed to generate a predictive model of long-term cancer-related behavioral symptoms clusters among breast cancer survivors 4 years after diagnosis.

Patients with early-stage breast cancer were included from the CANcer TOxicity trial (ClinicalTrials.gov identifier NCT01993498). Our outcome was the proportion of patients reporting cancer-related behavioral symptoms clusters 4 years after diagnosis (≥3 severe symptoms). Predictors, including clinical, behavioral, and treatment-related characteristics; Behavioral Symptoms Score (BSS; 1 point per severe cancer-related behavioral symptom at diagnosis); and a proinflammatory cytokine (interleukin 1b; interleukin 6; tumor necrosis factor α) genetic risk score were tested using multivariable logistic regression, implementing bootstrapped augmented backwards elimination. A 2-sided P less than .05 defined statistical significance.

In the development cohort (n = 3555), 642 patients (19.1%) reported a cluster of cancer-related behavioral symptoms at diagnosis, and 755 (21.2%) did so 4 years after diagnosis. Younger age (adjusted odds ratio for 1-year decrement = 1.012, 95% confidence interval [CI] = 1.003 to 1.020), previous psychiatric disorders (adjusted odds ratio vs no = 1.27, 95% CI = 1.01 to 1.60), and BSS (adjusted odds ratio ranged from 2.17 [95% CI = 1.66 to 2.85] for BSS = 1 vs 0 to 12.3 [95% CI = 7.33 to 20.87] for BSS = 5 vs 0) were predictors of reporting a cluster of cancer-related behavioral symptoms (area under the curve = 0.73, 95% CI = 0.71 to 0.75). Genetic risk score was not predictive of these symptoms. Results were confirmed in the validation cohort (n = 1533).

Younger patients with previous psychiatric disorders and higher baseline symptom burden have greater risk of long-term clusters of cancer-related behavioral symptoms. Our model might be implemented in clinical pathways to improve management and test the effectiveness of risk-mitigation interventions among breast cancer survivors.

This study aimed to explore the complex relationships among symptoms and symptom clusters in patients with gynecologic cancer receiving chemotherapy using symptom network analysis, and to identify core symptoms and core symptom clusters.

A cross-sectional study was conducted at the Affiliated Hospital of Jiangnan University from December 2023 to June 2024, including 221 patients with gynecologic tumors. Participants completed demographic and clinical information questionnaires and the Chinese version of the MD Anderson Symptom Inventory (MDASI-C). Univariate analysis and multiple linear regression were used to screen covariates, exploratory factor analysis to determine symptom clusters, and network analysis to identify core symptoms and core symptom clusters.

A total of 221 patients were included, with an average age of 58.73 years (SD = 11.50). Fatigue (n = 197, 89.1%) and lack of appetite (n = 192, 86.9%) were the most common symptoms, while fatigue (mean = 4.17, SD = 2.07) and distress (mean = 3.43, SD = 2.20) were the most severe symptoms. Several distinct symptom clusters were identified: sickness behavior, gastrointestinal, psychological, and side-effect clusters. In the constructed network, fatigue emerged as the most central symptom (rs = 1.28), while the sickness behavior cluster was identified as the most central symptom cluster (rs = 1.11).

Patients with gynecologic cancer undergoing chemotherapy commonly experience a range of symptoms. Our findings suggest that targeted interventions focusing on the sickness behavior symptom cluster may help reduce the overall symptom burden and assist caregivers in developing more effective symptom management strategies.

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern.

A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake.

Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.

Deterioration in the neurocognitive function of cancer patients referred to as "Chemobrain" is a devastating obstacle associated with cyclophosphamide (CYP). CYP is an alkylating agent, clinically utilized as an efficient anticancer and immunosuppressant. Coenzyme Q10 (CoQ10) is a worthwhile micronutrient with diverse biological activities embracing antioxidant, anti-apoptotic, and neuroprotective effects. The current experiment was designed for investigating the neuroprotective capability of CoQ10 versus CYP-elicited chemobrain in rats besides elucidating the causal molecular mechanisms. Male Sprague Dawley rats received CoQ10 (10 mg/kg, orally, once daily, for 10 days) and/or a single dose of CYP (200 mg/kg i.p. on day 7). CoQ10 counteracted CYP-induced cognitive and motor dysfunction as demonstrated by the findings of neurobehavioral tests (passive avoidance, Y maze, locomotion, and rotarod tests). Histopathological analysis further affirmed the neuroprotective abilities of CoQ10. CoQ10 effectually diminished CYP-provoked oxidative injury by restoring the antioxidant activity of catalase (CAT) enzyme while reducing malondialdehyde (MDA) levels. Besides, CoQ10 efficiently repressed CYP-induced neuronal apoptosis by downregulating the expression of Bax and caspase-3 while upregulating the Bcl-2 expression. Moreover, CoQ10 hampered CYP-provoked upregulation in acetylcholinesterase (AChE) activity. Furthermore, CoQ10 considerably augmented hippocampal neurogenesis by elevating the expressions of brain-derived neurotrophic factor (BDNF) and Ki-67. These promising neuroprotective effects can be credited to upregulating Wnt/β-catenin pathway as evidenced by the elevated expressions of Wnt-3a, β-catenin, and Phoshpo-glycogen synthase kinase-3 β (p-GSK-3β). Collectively, these findings proved the neuroprotective capabilities of CoQ10 against CYP-induced chemobrain through combating oxidative injury, repressing intrinsic apoptosis, boosting neurogenesis, and eventually upregulating the Wnt/β-catenin pathway.

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.

Background/Objectives: Cisplatin, a common chemotherapy agent, is well known to cause severe side effects in the gastrointestinal and nervous systems due to its toxic and pro-inflammatory effects. Although pharmacological manipulation of the endocannabinoid system (ECS) can alleviate these side effects, how chemotherapy affects the ECS components in these systems remains poorly understood. Our aim was to evaluate these changes. Methods: Male Wistar rats received cisplatin (5 mg/kg, i.p.) or saline on day 0 (D0). Immediately after, serial X-rays were taken for 24 h (D0). Body weight was recorded (D0, D1, D2 and D7) and behavioural tests were performed on D4. On D7, animals were euthanized, and gastrointestinal tissue, dorsal root ganglia (DRGs) and brain areas were collected. Expression of genes related to the ECS was assessed via Rt-PCR, while LC-MS/MS was used to analyse endocannabinoid and related N-acylethanolamine levels in tissue and plasma. Results: Animals treated with cisplatin showed a reduction in body weight. Cisplatin reduced gastric emptying during D0 and decreased MAGL gene expression in the antrum at D7. Despite cisplatin not causing mechanical or heat sensitivity, we observed ECS alterations in the prefrontal cortex (PFC) and DRGs similar to those seen in other chronic pain conditions, including an increased CB1 gene expression in L4/L5 DRGs and a decreased MAGL expression in PFC. Conclusions: A single dose of cisplatin (5 mg/kg, i.p.), subnoxious, but capable of inducing acute gastrointestinal effects, caused ECS changes in both gastrointestinal and nervous systems. Modulating the ECS could alleviate or potentially prevent chemotherapy-induced toxicity.

The aim of this network meta-analysis was to compare the improvement effects of various exercise interventions and mindfulness-based interventions to determine the best interventions for the improvement of cognitive impairment.

Seven databases were searched to screen randomized controlled trials of exercise interventions and mindfulness-based interventions to improve cognitive impairment. The network meta-analysis was performed using Revman 5.3, R 4.2.1 and ADDIS 1.16.8 software.

Thirty-four randomized controlled trials involving 14 interventions were included in the study. In terms of cognitive function, except for mindfulness-based stress reduction, all interventions showed significantly greater improvement in cognitive function compared with conventional therapy. Physical activity and Qigong showed better effect in improving executive function. In terms of improving verbal memory, compensatory cognitive training, neurofeedback training, Qigong, and sham Qigong were more effective than other interventions. On performing surface under the cumulative ranking curve analysis, acceptance and commitment therapy, neurofeedback training, Qigong, and mediation had the best effects on cognitive function, quality of life, executive function, and processing speed, respectively.

Mindfulness-based interventions were found to be more effective than exercise interventions for alleviating cognitive impairment. More robust randomized controlled trials focusing on acceptance and commitment therapy for cognitive impairment are required to support the current evidence.

Cyclophosphamide has drastically enhanced the expectancy and quality of life of cancer patients. However, it is accompanied by diverse neurological complications which are considered a dose-limiting adverse effect. Neurotoxicity caused by cyclophosphamide can manifest in numerous manners including anxiety, depression, motor dysfunction and cognitive deficits. This review article offers an overview on cyclophosphamide-induced neurotoxicity, providing a unified point of view on the possible underlying molecular mechanisms including oxidative brain damage, neuroinflammation, apoptotic neuronal cell death as well as disruption of the balance of brain neurotransmitters and neurotrophic factors. Besides, this review sheds light on the promising protective agents that have been investigated using preclinical animal models as well as their biological targets and protection mechanisms. Despite promising results in experimental models, none of these agents has been studied in clinical trials. Thus, there is lack of evidence to advocate the use of any neuroprotective agent in the clinical setting. Furthermore, none of the protective agents has been evaluated for its effect on the anticancer activity of cyclophosphamide in tumor-bearing animals. Therefore, there is a great necessity for adequate well-designed clinical studies for evaluation of the therapeutic values of these candidates. Conclusively, this review summarizes the molecular mechanisms accounting for cyclophosphamide-induced neurotoxicity together with the potential protective strategies seeking for downgrading this neurological complication, thus enhancing the quality of life and well-being of cancer patients treated with cyclophosphamide.

Chemotherapy for malignant tumors can cause brain changes and cognitive impairment, leading to chemotherapy-induced cognitive impairment (CICI). Current research on CICI has focused on breast cancer and Hodgkin's lymphoma. Whether patients with non-Hodgkin's lymphoma (NHL) undergoing chemotherapy have cognitive impairment has not been fully investigated.

To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.

The study included 100 NHL patients who were required to complete a comprehensive psychological scale including the Brief Psychiatric Examination Scale (MMSE) at two time points: before chemotherapy and within 2 wk of two chemotherapy courses. A language proficiency test (VFT), Symbol Number Pattern Test (SDMT), Clock Drawing Test (CDT), Abbreviated Daily Cognition Scale (ECog-12), Prospective and Retrospective Memory Questionnaire, and Karnofsky Performance Status were used to assess cognitive changes before and after chemotherapy.

The VFT scores for before treatment (BT) and after treatment (AT) groups were 45.20 ± 15.62, and 42.30 ± 17.53, respectively (t -2.16, P < 0.05). The CDT scores were 8 (3.5-9.25) for BT and 7 (2.5-9) for AT groups (Z -2.1, P < 0.05). Retrospective memory scores were 13.5 (9-17) for BT and 15 (13-18) for AT (Z -3.7, P < 0.01). The prospective memory scores were 12.63 ± 3.61 for BT and 14.43 ± 4.32 for AT groups (t -4.97, P < 0.01). The ECog-12 scores were 1.71 (1.25-2.08) for BT and 1.79 (1.42-2.08) for AT groups (Z -2.84, P < 0.01). The SDMT and MMSE values did not show a significant difference between BT and AT groups.

Compared to the AT group, the BT group showed impaired language, memory, and subjective cognition, but objective cognition and execution were not significantly affected.

Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.

IIrbesartan (IRB), an angiotensin II type 1 receptor (AT1R) antagonist, has been widely employed in the medical field for its effectiveness in managing hypertension. However, there have been no documented investigations regarding the immunostimulatory properties of IRB. To address this gap, this study has been performed to assess the neuroprotective impact of IRB as an immunostimulatory agent in mitigating acute neurotoxicity induced by cyclophosphamide (CYP) in rats. mRNA levels of nuclear factor erythroid 2 (Nrf-2), interleukin (IL)-18, IL-1β, and MMP-1 have been assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) has been evaluated to assess the oxidative stress. Additionally, macrophage inflammatory protein 2 (MIP2) has been evaluated using enzyme-linked immunosorbent assay (ELISA). Western blotting has been used to investigate the protein expression of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 (CASP-1), along with an assessment of histopathological changes. Administration of IRB protected against oxidative stress by augmenting the levels of GSH and SOD as well as reducing MDA level. Also, administration of IRB led to a diminishment in the brain levels of MIP2 and MMP1. Furthermore, it led to a suppression of IL-1β and IL-18 levels, which are correlated with a reduction in the abundance of NLRP3 and subsequently CASP-1. This study provides new insights into the immunomodulatory effects of IRB in the context of CYP-induced acute neurotoxicity. Specifically, IRB exerts its effects by reducing oxidative stress, neuroinflammation, inhibiting chemokine recruitment, and mitigating neuronal degeneration through the modulation of immune markers. Therefore, it can be inferred that the use of IRB as an immunomodulator has the potential to effectively mitigate immune disorders associated with inflammation.

Perceived cognitive impairment is a significant symptom experienced by breast cancer patients and may be affected by sleep quality. Coping styles have potential relevancies with both sleep quality and perceived cognitive impairment. However, the empirical evidence supporting their association among breast cancer patients is limited.

This study explored the associations between sleep quality, coping styles, and perceived cognitive impairment and tested the mediating role of coping styles in breast cancer patients.

A total of 294 breast cancer patients were included in this cross-sectional study. Patients were assessed using the Pittsburgh Sleep Index Scale, the Simplified Coping Styles Questionnaire, and the Functional Assessment of Cancer Therapy-Cognitive Functioning (Version 3) Scale. The data were analyzed using SPSS and Process macros.

The direct effect of sleep quality on reported cognitive impairment was significant (β = -0.245, P < .001). Furthermore, sleep quality was found to have a significant indirect effect on perceived cognitive impairment through positive coping style (β = -0.026, P < .05) and negative coping style (β = -0.131, P < .05).

Our research suggests that sleep quality has both a direct effect on perceived cognitive impairment and an indirect effect through positive and negative coping styles in breast cancer patients. Moreover, negative coping style had a more pronounced mediating effect than positive coping style.

Clinical medical staff could reduce the perceived cognitive impairment of breast cancer patients by improving their sleep quality and encouraging them to adopt a more positive coping style.

Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT) has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who were in remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.

Cancer-related cognitive impairment (CRCI) is commonly experienced by patients with cancer during treatment, and 35% of patients experience cognitive impairment after treatment completion. Impairments in memory, attention, executive functioning, and information processing speed are most reported and often negatively impact daily functioning and quality of life (QoL). Despite the large scale of reports, this adverse side effect is underinvestigated across common cancer types, and there is a lack of insight into the CRCI experience.

This qualitative synthesis aims to explore the evidence in relation to the experience of CRCI across common cancers. It also aims to understand the prevalence of CRCI across various cancer types, cognitive domains, and its impact on QoL and functional ability.

A comprehensive search of databases, including PubMed, American Psychological Association PsycINFO, CINAHL, and Scopus, will be conducted. A total of 2 independent reviewers will screen titles and abstracts for inclusion, followed by full-text screening. A third reviewer will resolve any arising conflicts in the process of data screening and inclusion. Subsequently, data extraction and quality assessment using the Critical Appraisal Skills Programme (CASP) tool will be conducted. The results will be analyzed using thematic analysis.

This review is part of a PhD program funded in January 2023. The review commenced in June 2023, and data analysis is currently in progress. The qualitative synthesis will explore the experiences of CRCI across common cancers. The included studies are expected to report on numerous cancer types such as breast cancer, prostate cancer, leukemia, and lung cancer. The included study types are most likely to be interviews, focus groups, and surveys with qualitative components.

This protocol highlights the need for a qualitative synthesis that will explore the experience of CRCI across common cancer types. It will provide valuable insight into the lived experience of CRCI and the cognitive domains that may be disproportionately affected. There is a growing demand for further management interventions and clinically tested treatments of CRCI and the qualitative exploration of patient experience is crucial for their development. This qualitative synthesis will inform future developments and will contribute to improving QoL after cancer.

DERR1-10.2196/56888.

For many cancer survivors, toxic side effects of treatment, lingering effects of the aftermath of disease and cancer recurrence adversely affect quality of life (QoL) and reduce healthspan. Data-driven approaches for quantifying and improving wellness in healthy individuals hold great promise for improving the lives of cancer survivors. The data-driven strategy will also guide personalized nutrition and exercise recommendations that may help prevent cancer recurrence and secondary malignancies in survivors.

This study examined executive functioning and episodic future thinking among Iranian women with breast cancer.

We recruited 40 healthy female community volunteers and 80 females with breast cancer (either currently undergoing chemotherapy n = 40 or not undergoing chemotherapy n = 40). Participants were assessed using cognitive tasks that assessed executive functioning and episodic future thinking and a measure of cancer-related fatigue.

Both cancer groups had poorer performance than controls on all measures of executive functioning and episodic future thinking. Those undergoing chemotherapy had poorer performance on all measures of executive functioning than those not undergoing chemotherapy. Cross-sectional mediation analyses revealed cancer-related fatigue had a significant mediator role between cancer group and executive functioning and episodic future thinking.

Those with breast cancer, particularly those undergoing chemotherapy, may be experiencing cognitive difficulties. These cognitive concerns should be considered by health teams as addressing these impairments may assist in improving quality of life and treatment adherence.

Mood disorders caused by chemotherapy have become more important as the survival of cancer patients increases, and new studies in this field will contribute to the prevention of this disorder. For this purpose, we used methotrexate, a chemotherapeutic agent frequently preferred in oncological cases. Mtx was administered as a single dose of 100 mg/kg intraperitoneally to male Wistar albino rats. Since oxidative stress plays an important role in chemotherapy-induced emotional impairment, n-acetylcysteine (NAC), a potent antioxidant, was administered at 500 mg/kg in two doses before Mtx administration. We evaluated anxiety and depression-like behaviors 24 h after Mtx administration, as well as some oxidative and inflammatory markers in blood serum and hippocampal tissue, acetylcholinesterase activity (AChE), and brain-derived neurotrophic factor (BDNF) release in hippocampal tissue. In rats, Mtx induced anxiety and depression-like behaviors as well as abnormalities in oxidative and inflammatory markers in blood serum and hippocampal tissue, increased AChE activity in hippocampal tissue, and decreased BDNF release. NAC treatment was found to ameliorate Mtx-induced anxiety and depression-like behaviors, increase antioxidant capacity, reduce oxidative stress and inflammatory response, and regulate AChE activity and BDNF release. In conclusion, the fact that NAC treatment of Mtx was effective is important for revising the treatment strategies for individuals suffering from this disorder, and this effect is thought to be related to the antioxidant and anti-inflammatory power of NAC.

An inverse association between cancer and Alzheimer's disease (AD) has been demonstrated; however, the association between cancer and mild cognitive impairment (MCI), and the association between cancer and cognitive decline are yet to be clarified. The AIBL dataset was used to address these knowledge gaps. The crude and adjusted odds ratios for MCI/AD and cognitive decline were compared between participants with/without cancer (referred to as C+ and C- participants). A 37% reduction in odds for AD was observed in C+ participants compared to C- participants after adjusting for all confounders. The overall risk for MCI and AD in C+ participants was reduced by 27% and 31%, respectively. The odds of cognitive decline from MCI to AD was reduced by 59% in C+ participants after adjusting for all confounders. The risk of cognitive decline from MCI to AD was halved in C+ participants. The estimated mean change in Clinical Dementia Rating-Sum of boxes (CDR-SOB) score per year was 0.23 units/year higher in C- participants than in C+ participants. Overall, an inverse association between cancer and MCI/AD was observed in AIBL, which is in line with previous reports. Importantly, an inverse association between cancer and cognitive decline has also been identified.

Chemotherapy-induced cognitive impairment (CICI) is one of the major adverse effects of antineoplastic drugs, which decrease the quality of life in cancer survivors. Extensive experimental and clinical research suggests that chemotherapeutic drugs generate an enormous amount of reactive oxygen species (ROS), contributing to oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal death, eventually leading to CICI. Despite the progress in exploring different pathological mechanisms of CICI, effective treatment to prevent CICI progression has not been developed yet. Nrf2 is the principal transcription factor that regulates cellular redox balance and inflammation-related gene expression. Emerging evidence suggests that upregulation of Nrf2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase neurogenesis. This review discusses the role of Nrf2 in CICI, how it responds to oxidative stress, inflammation, neurotoxicity, and potential Nrf2 activators that could be used to enhance Nrf2 activation in CICI.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.

Breast cancer often leads to cancer-related cognitive impairment (CRCI), which includes both objective and subjective cognitive deficits. While psychosocial interventions benefit quality of life and distress reduction, their impact on cognitive deficits is uncertain. This study evaluates the integration of a cognitive module into a digital psychosocial intervention for breast cancer patients.

In this randomized controlled trial (RCT), 88 recently diagnosed breast cancer (BC) patients will receive the ICOnnecta't program (control group) - a digital stepped intervention addressing a variety of psychosocial needs. The experimental group (n = 88) will receive ICOnnecta't plus a cognitive module. Assessments at baseline, 3, 6, and 12 months will measure the interventions' impact on cognition, emotional distress, medication adherence, quality of life, post-traumatic stress, work functioning and healthcare experience. Feasibility and cost-utility analyses will also be conducted.

The cognitive module includes three levels. The first level contains a cognitive screening using FACT-Cog Perceived Cognitive Impairment (PCI). Patients with PCI <54 progress to a cognitive psychoeducational campus (Level 2) with content on cognitive education, behavioural strategies and mindfulness. Patients with persistent or worsened PCI (≥6) after 3 months move to Level 3, an online cognitive training through CogniFit software delivered twice a week over 12 weeks.

This study assesses whether integrating a cognitive module into a digital psychosocial intervention improves objective and subjective cognition in breast cancer patients. Secondary outcomes explore cognitive improvement's impact on psychosocial variables. The research will contribute to testing efficacious approaches for detecting and addressing cognitive dysfunction in breast cancer patients.

ClinicalTrials.gov, NCT06103318. Registered 26 October 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06103318?term=serra-blasco&draw=2&rank=4.

Childhood is recognised as a period of immense physical and emotional development, and this, in part, is driven by underlying neurophysiological transformations. These neurodevelopmental processes are unique to the paediatric brain and are facilitated by augmented rates of neuroplasticity and expanded neural stem cell populations within neurogenic niches. However, given the immaturity of the developing central nervous system, innate protective mechanisms such as neuroimmune and antioxidant responses are functionally naïve which results in periods of heightened sensitivity to neurotoxic insult. This is highly relevant in the context of paediatric cancer, and in particular, the neurocognitive symptoms associated with treatment, such as surgery, radio- and chemotherapy. The vulnerability of the developing brain may increase susceptibility to damage and persistent symptomology, aligning with reports of more severe neurocognitive dysfunction in children compared to adults. It is therefore surprising, given this intensified neurocognitive burden, that most of the pre-clinical, mechanistic research focuses exclusively on adult populations and extrapolates findings to paediatric cohorts. Given this dearth of age-specific research, throughout this review we will draw comparisons with neurodevelopmental disorders which share comparable pathways to cancer treatment related side-effects. Furthermore, we will examine the unique nuances of the paediatric brain along with the somatic systems which influence neurological function. In doing so, we will highlight the importance of developing in vitro and in vivo paediatric disease models to produce age-specific discovery and clinically translatable research.

Sorafenib, an FDA-approved standard chemotherapy for advanced hepatocellular carcinoma, is associated with numerous adverse effects that significantly impact patients' physiological well-being. Consequently, identifying agents that mitigate these side effects while enhancing efficacy is crucial. Hesperetin, a flavone present in fruits and vegetables, possesses antioxidant, anti-inflammatory, and anti-cancer properties. This study aimed to investigate the hepatotoxic and neurotoxic effects of sorafenib and the potential protective role of hesperetin.

Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days. Behavioral assessments for anxiety and depressive-like behaviors were conducted. Additionally, evaluations encompassed apoptotic activity, mitochondrial integrity, liver enzyme levels, proliferation rates, and histopathological changes.

Combining hesperetin with sorafenib showed improvements in behavioral alterations, liver damage, brain mitochondrial dysfunction, and liver apoptosis compared to the sorafenib-only group in mice.

Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.

Many cancer patients experience serious cognitive problems related to their treatment, which can greatly affect their quality of life. The molecular mechanisms of this cancer chemotherapy-induced cognitive impairment (CICI) are unknown, thus slowing the development of preventative approaches. We hypothesized that cancer chemotherapies could induce cellular senescence in the brain, creating a pro-inflammatory environment and damaging normal brain communication. We tested this hypothesis using the common chemotherapeutic agent doxorubicin in two independent mouse models. In the first model, we used mice that express tdTomato under the pdkn2a (p16) promoter; p16 is a regulator of cellular senescence, and its upregulation is denoted by the presence of fluorescently tagged cells. Two weeks after exposure to three doses of 5 mg/kg doxorubicin, the number of tdTomato positive cells were increased nearly three-fold in both the cerebral cortex and the hippocampus. tdTomato staining co-localized with neurons, microglia, oligodendrocyte precursor cells, and endothelial cells, but not astrocytes. In the second model, we used APOE knock-in mice, since the APOE4 allele is a risk factor for CICI in humans and mouse models. We isolated RNA from the cerebral cortex of APOE3 and APOE4 mice from one to 21 days after a single dose of 10 mg/kg doxorubicin. Using NanoString analysis of over 700 genes related to neuroinflammation and RT-qPCR analysis of cerebral cortex transcripts, we found two-fold induction of four senescence-related genes at three weeks in the APOE4 mice compared to the APOE3 control mice: p21(cdkn1a), p16, Gadd45a, and Egr1. We conclude that doxorubicin promotes cellular senescence pathways in the brain, supporting the hypothesis that drugs to eliminate senescent cells could be useful in preventing CICI.

Chemotherapy-induced cognitive impairment (CICI) is a subject that requires critical solutions in neuroscience and oncology. However, its potential mechanism of action remains ambiguous. The aim of this study was to investigate the vital role of HuR in the neuroprotection of cyclosporin A (CsA) during methotrexate (MTX)-induced cognitive impairment. A series of Hu-antigen R (HuR) gain and loss experiments were used to examine cyclosporin A (CsA)-mediated translocation of HuR's ability to improve MTX-induced cognitive impairment through NCOA4-mediated ferritinophagy in vitro and in vivo. Obtained results show that the administration of CsA alleviated MTX-induced cognitive impairment in mice. The presence of MTX promoted the shuttling of HuR from the cytoplasm to the nucleus, whereas treatment with CsA increased cytoplasmic HuR expression levels and the levels of ferritinophagy-related proteins, such as NCOA4 and LC3II, compared to the MTX group. However, applying KH-3, an inhibitor of HuR, reversed CsA's impact on the expression of ferritinophagy-related proteins in the hippocampus and in vitro. Also, treatment with CsA attenuated microglial activation by altering Iba-1 expression and decreased TNF-α and IL-1β levels in mice hippocampi. Moreover, KH-3 neutralized CsA's effects on the expression of both Iba-1 and HuR in vivo and in vitro. In summary, CsA was confirmed to have a neuroprotective role in CICI. Its possible underlying mechanisms may be involved in the translocation of HuR. Mediating the translocation of HuR during CICI could mitigate neruoinflammation and neuronal apoptosis via NCOA4-mediated ferritinophagy and, thus, alleviate cognitive impairment in mice with CICI.

Cladribine is a purine nucleoside found to enhance toxic amyloid protein and cause memory impairment. Patients following chemotherapy treatment commonly suffer from cognitive deficits more prevalent in the elderly than adults. A previous research study revealed that cladribine has a high affinity to the brain, increases the level of amyloid precursor protein, and results in learning deficits. The study was designed to validate an animal model of cladribine administration to rats through mitochondrial oxidative stress, inflammation, apoptosis, tau phosphorylation, and amyloid-β (1-42) accumulation. In this study, all rats were orally given cladribine (0.5 and 1 mg/kg) for 28 days, resulting in impaired spatial memory confirmed by behavioural activity. On day 29, all rats were euthanized, and the hippocampal tissues were isolated and used for the estimation of neuroinflammatory markers, biochemicals parameters (glutathione, catalase, lipid peroxidation, and nitrite), amyloid-β (1-42) level, neurotransmitters, and nuclear factor kappa B analysis. Cladribine administration significantly elevated cytokines release, dysbalanced neurotransmitter concentration, and promoted the Aβ accumulation and hyperphosphorylation of tau protein. Our study outcome confirmed that cladribine produces cognitive impairment via activation of Nuclear factor kappa B, mitochondrial oxidative stress and dysbalanced of the endogenous antioxidant defence system.

Cyclophosphamide (CPA) is a chemotherapeutic drug used for various types of cancers. However, patients receiving CPA for long periods suffer cognitive impairment associated with difficulties in learning, decreased concentration, and impaired memory. Chemotherapy-induced cognitive impairment, known as chemobrain, has been attributed to enhanced oxidative stress and inflammatory response. The current study aimed to identify the phytoconstituents of Callistemon subulatus extract (CSE) using HPLC-ESI/MS-MS analysis and evaluate its neuroprotective activity against CPA-induced chemobrain in rats. Fourteen compounds were identified following HPLC analysis including, five phlorglucinols, four flavonol glycosides, a triterpene, and a phenolic acid. Forty rats were divided into five groups treated for ten days as follows; group I (control group), group II received CPA (200 mg/kg, i.p.) on the 7th day, groups III and IV received CSE (200 and 400 mg/kg respectively, orally) for ten days and CPA (200 mg/kg, i.p.) on the 7th day, and group V received only CSE (400 mg/kg, orally) for ten days. The administration of CSE effectively ameliorated the deleterious effects of CPA on spatial and short-term memories, as evidenced by behavioral tests, Y-maze and passive avoidance. Such findings were further confirmed by histological examination. In addition, CSE counteracted the effect of CPA on hippocampal acetylcholinesterase (AChE) activity enhancing the level of acetylcholine. Owing to the CSE antioxidant properties, it hindered the CPA-induced redox imbalance, which is represented by decreased catalase and reduced glutathione levels, as well as enhanced lipid peroxidation. Therefore, CSE may be a promising natural candidate for protection against CPA-induced chemobrain in cancer patients.

Chemotherapy-induced cognitive impairment (CICI) is a general term describing cognitive dysfunction during/after treatment with chemotherapeutic agents. CICI represents a significant medical problem due to its increasing prevalence with the lack of robust therapeutic approaches. This study aimed at investigating the effects of chronic treatment with amisulpride (5 mg/kg/day) in the management of 5-fluorouracil (5-FU)-induced cognitive deficits in Wistar rats. Rats received 5 intraperitoneal injections of 5-FU (25 mg/kg every 3 days). 5-FU treatment induced impairments in spatial learning (reduction in object location discrimination ratio) and non-spatial learning (reduction in novel object recognition discrimination ratio). Moreover, 5-FU induced a decrease in the activity of the Wnt/GSK-3β/β-catenin pathway with a decrease in brain-derived neurotrophic factor (BDNF) level in the hippocampus. These changes were associated with an increase in the expression of the pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in hippocampal tissue sections accompanied by a decrease in the number of Ki-67 positive cells (indicating a decrease in proliferative capacity), a decrease in the Nissl's granules optical density (denoting neurodegeneration), a decrease in the number of viable intact neurons with an increase in the expression of β-amyloid and caspase-3. Amisulpride enhanced Wnt/GSK-3β/β-catenin signaling, increased BDNF levels, and abrogated 5-FU-induced neuroinflammation, apoptosis, β-amyloid accumulation, and neurodegenerative changes with an improvement of cognitive performance. This study draws attention to the pro-cognitive effects of amisulpride in 5-FU-exposed rats that could be attributed to enhancing hippocampal Wnt/GSK-3β/β-catenin signaling pathway, and this could offer a promising therapeutic option for subjects with CICI.

Chemotherapy is one of the most widely used treatments for breast cancer (BC). However, there is evidence of side effects like cognitive changes related to the chemotherapy treatment. The aim of the study was not only to summarize the existing evidence on the relationship between chemotherapy and cognitive performance in women with BC but also to identify additional consequences and aspects associated with these impairments. We conducted a systematic review with meta-analysis and meta-regression to present updated information on the matter. We retrieved data from the databases PubMed, Web of Science, PsycINFO, CINAHL, and Scopus. Twenty studies comprising over 2,500 women were examined and the results indicated that chemotherapy can compromise cognition in women with BC (-1.10 OR [95%CI: -1.81 to -0.74], P<0.01), with working memory (-0.49 OR [95%CI: -0.85 to -0.13], P=0.03) being the most affected among the domains. Furthermore, additional data indicated that cognitive impairment is most likely amid women with BC having a lower education level (Q=4.85, P=0.02). Our results suggested that chemotherapy affects cognitive functions in women with BC, and certain characteristics can worsen the deterioration. A comprehensive study of women with breast cancer and existing predictors contributes to optimized personal journeys, elevated life prospects, and advanced care that can also aid prognosis and therapeutic approaches.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.

Anthracyclines, chemotherapeutic agents used to treat common forms of cancer, increase cardiovascular (CV) complications, thereby necessitating research regarding interventions to improve the health of cancer survivors. Vascular dysfunction, which is induced by anthracycline chemotherapy, is an established antecedent to overt CV diseases. Potential treatment options for ameliorating vascular dysfunction have largely been understudied. Furthermore, patients treated with anthracyclines have impaired cognitive function and vascular dysfunction is an independent risk factor for the development of mild cognitive impairment. Here, we will focus on: anthracycline chemotherapy associated CV diseases risk; how targeting mechanisms underlying vascular dysfunction may be a means to improve both CV and cognitive health; and research gaps and potential future directions for the field of cardio-oncology.

To compare subjective and objective cognitive functions among patients at the following three stages of treatment for colorectal cancer (CRC): new diagnosis (Group A), ≤2 years since chemotherapy completion (Group B), and >2 years since chemotherapy completion (Group C).

A comparative cross-sectional approach was used in this study. The Functional Assessment of Cancer Therapy-Cognitive Function questionnaire and neuropsychological assessments were used to assess patients' subjective cognitive function, attention, memory, and executive functions. A total of 63 patients with stage I to III CRC were recruited from a medical center in northern Taiwan. We performed one-to-one-to-one propensity score matching to identify 36 individuals as eligible for this study. A generalized estimating equation was used to compare subjective and objective cognitive functions.

We observed no significant between-group differences in subjective cognitive function and objective performance in overall cognition and memory. Group B had significantly longer reaction time in attention and processing speed than did Group A. Adjuvant chemotherapy had significantly deleterious effects on attention and processing speed in patients with CRC. These cognitive symptoms last for approximately 2 years after the completion of chemotherapy.

The early detection of cancer-related cognitive impairment is necessary for managing symptom distress. Future studies with a large sample size and longitudinal design may elucidate the trajectory of specific cognitive functions. Developing nursing interventions aimed at improving attention and executive function in patients with CRC are needed.

Despite the importance of chemotherapy-associated adverse events in oncology practice and the broad range of interventions available to mitigate them, limited systematic efforts have been made to identify, critically appraise and summarize the totality of evidence on the effectiveness of these interventions. Herein, we review the most common long-term (continued beyond treatment) and late or delayed (following treatment) adverse events associated with chemotherapy and other anticancer treatments that pose major threats in terms of survival, quality of life and continuation of optimal therapy. These adverse effects often emerge during and continue beyond the course of therapy or arise among survivors in the months and years following treatment. For each of these adverse effects, we discuss and critically evaluate their underlying biological mechanisms, the most commonly used pharmacological and non-pharmacological treatment strategies, and evidence-based clinical practice guidelines for their appropriate management. Furthermore, we discuss risk factors and validated risk-assessment tools for identifying patients most likely to be harmed by chemotherapy and potentially benefit from effective interventions. Finally, we highlight promising emerging supportive-care opportunities for the ever-increasing number of cancer survivors at continuing risk of adverse treatment effects.