Chemobrain Research Articles

Abstract # 1778 Intranasal administration of mesenchymal stem cells promote recovery from cisplatin-induced neurological and cognitive impairments

Cognitive impairments are common side effects of chemotherapy treatment that may persist after the secession of intervention. Here, we tested the effects of nasal mesenchymal stem cell (MSC) administration on the neurotoxic side effects of cisplatin treatment. Adult C57Bl/6J mice were treated with saline or cisplatin (2.3 mg/kg) for two cycles. One million MSC were administered intranasally at 48 h and 96 h after the last injection of cisplatin. 14 days after the second MSC administration, novel object/place recognition (NOPR) and the Y-maze tests were performed as a parameter of cognitive function. Synaptic mitochondrial function was analyzed using the Seahorse XFe 24 Analyzer. Brains were stained for myelin basic protein (MBP) as a measure of white matter integrity and doublecortin (DCX) as a measure of neurogenesis. Two cycles of cisplatin treatment impaired cognition as tested in NOPR and Y-maze which paralleled a marked decrease in spare respiratory capacity of the synaptosomes. Furthermore, cisplatin treatment increased coherency of MBP fibers and decreased DCX staining in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, suggesting impaired neurogenesis. Administration of MSC after chemotherapy treatment promoted recovery from cisplatin-induced cognitive impairment and restored mitochondrial function as well as white matter damage and the loss of DCX+ cells. Our data suggest that treatment with MSC may represent a realistic therapeutic strategy for the prevention of chemotherapy-induced cognitive impairment.

Early manifestation of mild cognitive impairment in B-cell non-Hodgkin’s lymphoma patients receiving CHOP and rituximab-CHOP chemotherapy

Existing evidence suggests that pro-inflammatory cytokines increases during chemotherapy which plays an intermediary role in Chemotherapy related cognitive impairment (CRCI) and thyroid dysregulation. Previous studies suggest that thyroid hormones are essential for neuronal development and neurotransmitter release. CHOP regimen has been the backbone of Non-Hodgkin's lymphoma (NHL) treatment from a decade but rituximab addition to CHOP (R-CHOP) has improved cure rates. However, their adverse event profile on behavior is not well studied on patients. In this study total 68 NHL patients were enrolled and divided equally in 2 groups as CHOP receiving (n=34) and R-CHOP receiving (n=34). Effects of R-CHOP and CHOP regimen on thyroid function, pro-inflammatory cytokines and cognitive function were determined at four time points that was from one day before 1st (TP0), 2nd (TP1), 3rd (TP2) and 4th (TP3) cycle of chemotherapy. Results indicated significant increase in levels of pro-inflammatory cytokines after each time point from TP0 to TP3of chemotherapy. Thyroid hormone levels i.e. T3, T4 were found significantly decreased and TSH was increased after each time point of both groups. MMSE score was found significantly decreased after each cycle of both groups. However, an inverse association was found between IL-1β levels with TSH by applying correlation coefficient. Cognitive function was decreased in patients with decreased T3 and T4 levels and increased TSH. To conclude, patients receiving R-CHOP regimen were found to have more increased IL-6 and IL-1β with more cognitive decline and thyroid abnormality as comparison to CHOP receiving patients.

Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer

Minocycline is purported to have neuroprotective properties in experimental models of some human neurologic diseases, and has therefore been identified as a putative neuroprotectant for chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. However, because its mechanism of action is believed to be mediated through anti-inflammatory, anti-apoptotic, and anti-oxidant pathways, co-administration of minocycline with chemotherapeutic agents has the potential to reduce the efficacy of anticancer drugs. The objective of this study is to evaluate the effect of minocycline on the activity of the AC chemotherapeutic regimen (Adriamycin [doxorubicin], Cytoxan [cyclophosphamide]) in in vitro and in vivo models of triple-negative breast cancer (TNBC). Clonogenic and methylthiazol tetrazolium (MTT) assays were used to assess survival and viability in two TNBC cell lines treated with increasing concentrations of AC in the presence or absence of minocycline. Biomarkers of apoptosis, cell stress, and DNA damage were evaluated by western blot. The in vivo effects of AC and minocycline, each alone and in combination, were assessed in a xenograft model of TNBC in female athymic nude mice by weekly tumor volume measurement, body and organ weight measurement, and histopathology. Apoptosis and proliferation were characterized by immunohistochemistry in the xenografts tumors. Brains from tumor-bearing mice were evaluated for microglial activation, glial scars, and the proportion of neural progenitor cells. Data from these in vitro and in vivo studies demonstrate that minocycline does not diminish the cytotoxic and tumor-suppressive effects of this chemotherapeutic drug combination in TNBC cells. Moreover, minocycline appeared to prevent the reduction in doublecortin-positive neural progenitor cells observed in AC-treated mice. We posit that minocycline may be useful clinically for its reported neuroprotective activity in breast cancer patients receiving AC without loss of chemotherapeutic efficacy.

Impact of Treatments to Improve Cognitive Function and Quality of Life on Cancer Patients with Carcinoma of the Testes

Testicular cancer is one of the most common and most treatable cancers in men aged 15-49 years. The high survival rates mean that it is essential to maintain quality of life and minimize adverse effects associated with treatment. Both malignant tumors and the modalities used to treatment them can have adverse effects from both a psychosocial and a neurocognitive function perspective. Recently, attention has focused on the negative impact of the disease and its treatment on the brain and on cognitive function, which can result in a form of neurocognitive dysfunction known as "chemo brain" or "chemo fog". Both cancer itself and the modalities used to treat it are associated with neurotoxicity and cognitive deficit, which are manifest in key areas of cognitive function. These problems may adversely affect both patients undergoing treatment and those in remission, with a consequent reduction in quality of life. Because many patients survive testicular cancer, it is important to understand the characteristics, range, and time course of disease symptoms, treatment, and side effects, all of which can lead to long-term physical, psychological, and social problems. Testicular cancer has a high potential for cure; therefore, patients suffer not only short-term but also long-term side effects associated with therapy. This article aims to offer a complete and concise overview of cognitive dysfunction and quality of life for patients with testicular cancer. It would be beneficial if research into testicular cancer also focused on the relationships between psychosocial factors, psychological disorders, and cognitive function. cognitive functions - quality of life - sexuality - body imageThe author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 1. 12. 2015Accepted: 20. 3. 2016.

The Feasibility of Using Metacognitive Strategy Training to Improve Cognitive Performance and Neural Connectivity in Women with Chemotherapy-Induced Cognitive Impairment

Objective: To evaluate the feasibility and preliminary effect of metacognitive strategy training (MCST) on cognitive performance and on neural connectivity in the frontoparietal network in women with chemotherapy-induced cognitive impairment (CICI) following treatment for breast cancer. Methods: A single-group pre/post study was conducted. After completing the baseline assessment battery and neuroimaging, the participants completed a 12-session MCST intervention. Following the completion of the intervention, the subjects completed the same assessment battery and neuroimaging as was completed at baseline within 4 weeks after the intervention. The key inclusion/exclusion criteria for this study were: completed chemotherapy for treatment of breast cancer, no other neurological or psychiatric diagnoses, self-reported CICI, and no contraindications to the use of MRI. Results: MCST had a small-to-large positive effect on all primary (cognitive) and secondary (quality of life and psychosocial) behavioral outcome measures (r = -0.12 to -0.88). There was also a positive change in functional connectivity in a frontoparietal cognitive control network connection in 6 of the 10 subjects, which was correlated to changes in the behavioral measures. Conclusions: This study found that MCST was associated with a positive effect on cognitive performance and neural connectivity in women with CICI following treatment for breast cancer.

Abstract 4782: Cisplatin induces mitochondrial damage and hippocampal neurotoxicity: a potential mechanism for chemotherapy-related cognitive impairment

Abstract Advances in cancer treatment, chemotherapy in particular, have substantially increased the number of long-term cancer survivors. However, these drugs often have neurotoxic effects that impair cognitive function, thereby diminishing the quality of life of millions of cancer survivors. Chemotherapy-related cognitive impairment (CRCI, chemo-brain) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. Cisplatin is used to treat breast cancer and advanced ovarian cancer among other malignancies. Notably, more than 30% of advanced ovarian cancer patients develop CRCI during and after cisplatin-based chemotherapy. A plausible explanation for CRCI is that cisplatin might impair the structure and functions of neurons in brain regions involved in learning and memory, such as the hippocampus. We have recently identified mitochondrial dysfunction and increased oxidative stress as a mechanism through which cisplatin causes hippocampal cell death, and severe dendritic damage in surviving neurons. The aims of this study were to examine the effect of the antioxidant N-acetylcysteine (NAC) in mitigating cisplatin-induced hippocampal damage and assesse the effect of cisplatin on cognitive performance in a rat model. At a high dose, cisplatin (1μM) induced ∼35% increase in caspase-9 activation in primary rat hippocampal neurons, whereas at a substantially lower dose, cisplatin (0.1μM) induced non-reversible damage to dendritic spines and branches. Both doses produced severe mitochondrial respiratory deficits and significant ROS production. Delayed treatment with NAC partially mitigated neuronal apoptosis and ameliorated cisplatin induced dendritic spine loss. When administered to adult Sprague Dawley rats, cisplatin (3 mg/kg) administered for two consecutive days caused ∼40% reduction in the number of dendritic spines in CA1 and CA3 hippocampal neurons. Lastly, cognitive testing of rats treated with a chronic cisplatin regimen, revealed significant deficits in hippocampus-dependent tasks. Rats were given weekly cisplatin (5mg/kg, i.p.) or saline injections for 4 weeks and then trained in Context-Object Discrimination, 6 weeks later (n = 7,8). Cisplatin-treated rats were impaired in discriminating between the out-of-context and in-context object. Mitochondrial dysfunction provokes free radical production, with resulting loss of dendritic spines. When administered to rats, cisplatin causes hippocampal neuronal and mitochondrial damage, as well as cognitive deficits, supporting that role of mitochondrial toxicity in the mechanisms of cisplatin-induced CRCI. Importantly the data demonstrates that these processes can be potentially mitigated with administration of the clinically available antioxidant, NAC. The effect of NAC in ameliorating cisplatin induced CRCI in rats is being evaluated. Citation Format: Naomi Lomeli, Jennifer Czerniawski, Kaijun Di, John Guzowski, Daniela Bota. Cisplatin induces mitochondrial damage and hippocampal neurotoxicity: a potential mechanism for chemotherapy-related cognitive impairment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4782.

What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research.

Cancer-related cognitive impairment (CRCI) is an important clinical problem for cancer patients and survivors. In this review, we summarize studies investigating the occurrence of impaired cognition in patients with haematological malignancies. Most published studies focus on survivors of childhood acute lymphoblastic leukaemia and primary central nervous system lymphoma. We also discuss studies conducted in acute myeloid leukaemia, myelodysplastic syndromes, chronic myeloid leukaemia, Hodgkin lymphoma (HL), non-HL and chronic lymphocytic leukaemia. Although research in this area is still emerging, it appears that a subsetof chemotherapy-treated haematological malignancy survivors experience CRCI. Future research should focus on expanding the literature reviewed here with larger studies appropriately powered to assess cognition via objective andsubjective measures in a longitudinal fashion to tease apart the impact of disease and the various forms of cancer treatment.

Chemotherapy-related cognitive impairment in older patients with cancer.

Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer.

Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin.

Chemotherapy-induced cognitive impairment, known also as “chemobrain”, is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional neurochemical and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced cognitive disorders.

Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy.

The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(-)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(-) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(-) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(-) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN.

A feasibility study exploring the role of pre-operative assessment when examining the mechanism of 'chemo-brain' in breast cancer patients.

BackgroundWomen receiving chemotherapy treatment for breast cancer may experience problems with their memory and attention (cognition), which is distressing and interferes with quality of life. It is unclear what causes or contributes to the problems they report: psychological distress, fatigue, coping style, or specific biological changes for example to pro inflammatory cytokines. Research shows however, that approximately a third of women with breast cancer perform poorly on tests of cognition before commencing chemotherapy. We aimed to examine the acceptability and relevance of pre-surgical assessments (bloods, brain imaging, cognitive tests and self-report questionnaires) when investigating the phenomenon of ‘chemo-brain’ and investigate whether inflammatory markers mediate chemotherapy-induced neuropsychological impairments in women treated for breast cancer.MethodsWomen with early stage breast cancer completed neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post-surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were measured at the same time points and brain imaging was performed at T1 and T3.ResultsIn total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy). Prior to the start of chemotherapy a decline in cognitive performance compared to baseline was observed in one participant. At T3 women who received chemotherapy reported poorer quality of life and greater fatigue. Increases in soluble tumour necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were inversely correlated with grey matter volume (GMV) of the right posterior insula in both groups. At T3, the chemotherapy group displayed a greater reduction in GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal gyrus.ConclusionsPre-operative recruitment to the study was challenging; however, the lack of significant changes in blood cytokine levels and neuropsychological tests at T2 implies that post surgery may be a valid baseline assessment, but this needs further investigation in a larger study. The preliminary results support the hypothesis that chemotherapy induced fatigue is mediated by a change in peripheral cytokine levels which could explain some symptoms of ‘chemo brain’ experienced by patients.

Sex-specific effects of cytotoxic chemotherapy agents cyclophosphamide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus - an aging connection.

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis.

Metformin Prevents Cisplatin-Induced Cognitive Impairment and Brain Damage in Mice.

RationaleChemotherapy-induced cognitive impairment, also known as ‘chemobrain’, is now widely recognized as a frequent adverse side effect of cancer treatment that often persists into survivorship. There are no drugs available to prevent or treat chemotherapy-induced cognitive deficits. The aim of this study was to establish a mouse model of cisplatin-induced cognitive deficits and to determine the potential preventive effects of the anti-diabetic drug metformin.ResultsTreatment of C57/BL6J mice with cisplatin (cumulative dose 34.5mg/kg) impaired performance in the novel object and place recognition task as well as in the social discrimination task indicating cognitive deficits. Co-administration of metformin prevented these cisplatin-induced cognitive impairments. At the structural level, we demonstrate that cisplatin reduces coherency of white matter fibers in the cingulate cortex. Moreover, the number of dendritic spines and neuronal arborizations as quantified on Golgi-stained brains was reduced after cisplatin treatment. Co-administration of metformin prevented all of these structural abnormalities in cisplatin-treated mice. In contrast to what has been reported in other models of chemobrain, we do not have evidence for persistent microglial or astrocyte activation in the brains of cisplatin-treated mice. Finally, we show that co-administration of metformin also protects against cisplatin-induced peripheral neuropathy.ConclusionIn summary, we show here for the first time that treatment of mice with cisplatin induces cognitive deficits that are associated with structural abnormalities in the brain. Moreover, we present the first evidence that the widely used and safe anti-diabetic drug metformin protects against these deleterious effects of cancer treatment. In view of the ongoing clinical trials to examine the potential efficacy of metformin as add-on therapy in patients treated for cancer, these findings should allow rapid clinical translation.

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

Prevalence of cognitive impairment in patients with hematologic cancers preceding stem cell transplantation: Program for healthy aging.

32 Background: Older adults, 65 years of age and older, with hematologic cancers may be at higher risk for cognitive impairment. It is postulated that the etiology of cognitive impairment in cancer may a combination of age-related and chemotherapy related cognitive impairment. Methods: We conducted a retrospective cohort analysis, of older adult patients 65 years and older evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through March 31, 2015. Cognitive assessment was evaluated through personal interview, and the Montreal cognitive assessment, functional assessment utilizing ADLs and IADLs. Screening for depression was conducted with the PHQ-9. Patients were interviewed regarding risk factors for dementia including depression, concussions, alcohol abuse, and family history of dementia. Level of education was assessed. Patients were euthymic. Cognitive impairment was defined as an abnormal MOCA without functional impairment, dementia was defined as an abnormal MOCA with functional impairment. Imaging and assessment for reversible factors of memory loss was conducted. SAS 9.4 (SAS Institute INC, Cary, NC) was used for data analysis. Results: The majority of these 62 patients had received chemotherapy for more than 2 years. Cognitive impairment and/or dementia were identified in 50 (80.6%) patients. Types of dementia included Alzheimer’s disease (n = 4, 8%), vascular dementia (n = 5, 10 %), and mixed dementia (n = 15, 30%).Mild cognitive impairment was evidenced in 14 cases (28%) The majority of cases of dementia with known stage were early stage dementia (n = 13, 72.2%), moderate stage dementia (n = 3, 16.7%), and advanced or severe dementia (n = 2, 11.1%). Brain imaging was performed identifying white matter microischemic changes, cerebrovascular accidents and brain atrophy in some cases. No significant thyroid abnormalities, B12 deficiency or other reversible causes were identified. Conclusions: Cognitive impairment and dementia are prevalent in older patients with hematologic malignancies. Identification and management of this condition may prevent delirium and hospital complications during stem cell transplantation.

The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain".

Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis.

Chemotherapy-related Cognitive Impairment and Quality of Life in People with Colon Cancer: The Mediating Effect of Psychological Distress

The purpose of this study was to test the mediating effect of psychological distress in the relationship between chemotherapy related cognitive impairment (CRCI) and quality of life (QOL) in people with cancer. A purposive sample of 130 patients undergoing chemotherapy was recruited for the cross-sectional survey design. Data were collected from November 2014 to June 2015. The instruments were K-MMSE (Korean Mini-Mental State Examination), Everyday Cognition (ECog), Hospital Anxiety Depression Scale (HADS), and Functional Assessment of Cancer Therapy-General (FACT-G). Data were analyzed using descriptive statistics, correlation, and multiple regression using Baron and Kenny steps for mediation. The mean score for objective cognitive function was 27.95 and 69.32 for perceived cognitive decline. Overall quality of life was 91.74. The mean score was 17.52 for psychological distress. The prevalence was 56.2% for anxiety and 63.1% for depression, and 20.0% for CRCI. There were significant correlations among the variables, objective cognitive function and self-reported cognitive decline, psychological distress, and quality of life. Psychological distress was directly affected by CRCI. (R²=29%). QOL was directly affected by CRCI. Psychological distress and CRCI effected QOL (R²=43%). Psychological distress had a partial mediating effect (β=-.56, p<.001) in the relationship between self-reported cognitive decline and quality of life (Sobel test: Z=-5.08, p<.001). Based on the findings of this study, nursing intervention programs focusing on managing cognitive decline, and decreasing psychological distress are highly recommended to improve quality of life in cancer patients.

Effect of Cancer Symptoms and Fatigue on Chemotherapy-related Cognitive Impairment and Depression in People with Gastrointestinal Cancer

The purpose of this study was to test a hypothetical model of chemotherapy-related cognitive impairment (CRCI) and depression in people with gastrointestinal cancer. A purposive sample of 198 patients undergoing chemotherapy was recruited from November 2014 to July 2015. The instruments were Everyday Cognition (ECog), Hospital Anxiety Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and M. D. Anderson Symptom Inventory-Gastrointestinal Cancer Module. Data were analyzed using descriptive statistics, correlation, and path analysis. CRCI was directly affected by cancer symptoms (β=.19, p=.004) and fatigue (β=.56, p<.001)(R²=47.2%). Depression was directly affected by fatigue (β=.48, p<.001) and CRCI (β=.27, p<.001). However, The impact of cancer symptoms on depression was confirmed through the mediating effect of CRCI. Results indicate that in patients with gastrointestinal cancer undergoing chemotherapy along with the direct physiologic effects (fatigue, symptoms) of cancer treatment may have altered cognitive function leading to depression.

Environmental enrichment protects against cognitive impairment following chemotherapy in an animal model.

Clinical studies indicate that up to 70% of cancer patients who receive chemotherapy experience cognitive impairment. The present study investigated environmental enrichment as a protective factor against the adverse effects of anticancer drugs on cognitive and biological processes in an animal model. Adult rats were housed in group cages with environmental stimulation or in standard cages for 3 months, before receiving 3 weekly injections of methotrexate + 5-fluorouracil, or equal volumes of saline. Rats were then administered tests of learning and memory that are sensitive to hippocampal or frontal lobe dysfunction. The relationship between cognitive performance and hippocampal neurogenesis was examined through sensitive time-dependent measures of neuronal maturation. Chemotherapy-treated rats in the standard environment were impaired on tests of spatial memory, nonmatching-to-sample (NMTS) rule learning, and delayed-NMTS. Chemotherapy-treated rats in the enriched environment performed at or near normal levels. The performance of the chemotherapy groups on the hippocampus-sensitive, spatial memory and delayed-NMTS tests correlated with neurogenesis levels. The results show that environmental enrichment can reduce the risk of chemotherapy-induced cognitive impairment, in part by promoting neuronal differentiation and growth during cell maturation. As well, they point to the importance of lifestyle factors in treating or preventing adverse effects of anticancer drugs on cognitive function. (PsycINFO Database Record

What is “chemo brain”?

What is “chemo brain”?