Chemobrain Research Articles

Neuroprotective effect of Mulmina™ against chemotherapy-induced cognitive decline in normal mice.

The aim of the present study was to evaluate a marketed formulation against chemotherapy-induced cognitive dysfunction. The formulation, Mulmina™, contains natural compounds which are known to help in improving function as well as in preventing cognitive decline. All of the phytoconstituents in the formulation have been tested individually but this is the first study where such a formulation has been evaluated against chemotherapy-induced cognitive decline (CICD) in a mouse model. CICD was induced by cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and 5-fluorouracil (5 mg/kg) (CMF), administered intraperitonially. CMF was administered in three cycles, with one injection per week for three weeks. The decline in cognition of the mice was evaluated by a test of locomotor activity (Open Field Test) followed by a test for spatial memory (Morris Water Maze). Biochemical parameters evaluated include brain cytokine levels and BDNF levels via ELISA. Hematological counts were also performed to evaluate any changes in blood profile using a veterinary blood cell counter. Levels of oxidative stress markers with respect to catalase activity and lipid peroxidation were also evaluated in the brain using UV-spectrophotometric analysis. Mulmina™ was able to show significant improvement in cognitive function post chemotherapy when compared to the untreated animals. Apart from improvement in spatial memory, there was also an improvement in biochemical parameters. The particular combination of phytochemicals in Mulmina™ proved themselves successful in alleviating the CICD in this preliminary study and pave a path for future studies which can establish the solid grounds with respect to molecular and pharmacological basis for the mechanism of action of Mulmina™.

Cognitive Dysfunction and Neurophysiologic Mechanism of Breast Cancer Patients Undergoing Chemotherapy Based on Resting State Functional Magnetic Resonance Imaging

We studied chemotherapy-related cognitive impairment via resting state (RS)-functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 19 cases of patients with early breast cancer. White matter neuropsychological test treatment were carried out before and after chemotherapy, RS-fMRI, and DTI evaluation. In RS-fMRI with regional homogeneity (ReHo) reflects brain activity. In the DTI with fractional anisotropy (FA) reflect the integrity of the white matter. Determining the region of interest by image analysis, we calculated the neuropsychologic test score using the paired t-test and FA change ReHo values of regions of interest. Finally after the test treatment, in the chemotherapy group for pairing correlation analysis t-test scores change in meaningful inspection and change ReHo and FA. Chemotherapy after chemotherapy than before chemotherapy difference memory test and self-evaluation of cognitive (P < 0.05). ReHo value increases occurred in the right orbitofrontal region and the left dorsolateral prefrontal cortex. Declines in brain regions were the anterior inferior cerebellar lobe, cerebellar lobe, right middle temporal gyrus and the superior temporal gyrus, the lower right of the center area, and the central gyrus. This prospective study on resting state and RS-fMRI functional magnetic resonance DTI study DTI sequence combination chemotherapy for breast cancer-related cognitive disorders supports the "chemo brain" point of view. Chemotherapy can cause memory decline, accompanied by a partial area of the brain and white matter integrity in brain activity changes. Prompt clinical treatment RS-fMRI and DTI have potential applications in assessing chemotherapy-related cognitive impairment.

Network-level functional connectivity alterations in chemotherapy treated breast cancer patients: a longitudinal resting state functional MRI study

BackgroundPrevious studies have found abnormal structural and functional brain alterations in breast cancer survivors undergoing chemotherapy. However, the network-level brain changes following chemotherapy remain unknown. The purpose of this study was to investigate the dynamic changes of large-scale within- and between-network functional connectivity in chemotherapy-treated breast cancer patients.MethodsSeventeen breast cancer patients were evaluated with resting state functional MRI (rs-fMRI), neuropsychological tests and blood examination before postoperative chemotherapy (t0), one week after completing chemotherapy (t1) and six months after completing chemotherapy (t2). Nineteen age- and education level-matched healthy controls (HC) were also recruited. Independent components analysis (ICA) was performed to assess network component using rs-fMRI data. The functional network changes were then correlated with cognitive assessment scores and blood biochemical indexes.ResultsOne-way repeated measures ANOVA revealed significantly changed within-network functional connectivity in the anterior and posterior default mode network (ADMN and PDMN), left and right frontoparietal network (LFPN and RFPN), visual network and self-referential network. Post-hoc test showed that decreased within-network functional connectivity in ADMN, PDMN, LFPN, RFPN, SRN and central network one week after chemotherapy and increased six months after chemotherapy (all P < 0.05). As for the between-network functional connectivity, the PDMN- sensorimotor network connectivity showed the same tendency. Most of these within- and between-network functional connectivity changes were negatively associated with blood biochemical indexes and cognitive assessment scores (all P < 0.05).ConclusionsThese results indicated that chemotherapy may induce widespread abnormalities in resting state networks, which may serve as a potential biomarker of chemotherapy related cognitive impairment, providing insights for further functional recovery treatment.

Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: Emphasis on the modulation of oxidative stress and neuroinflammation

Chemotherapy-induced cognitive dysfunction (chemobrain) is one of the major complaints for cancer patients treated with chemotherapy such as Doxorubicin (DOX). The induction of oxidative stress and neuroinflammation were identified as major contributors to such adverse effect. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound, that exhibits unique context-dependent antioxidant activity. It exhibits pro-oxidant effects in cancer cells, while it is a potent antioxidant and cytoprotective in normal cells. The present study was designed to investigate the potential neuroprotective effects of CAPE against DOX-induced cognitive impairment. Chemobrain was induced in Sprague Dawley rats via systemic DOX administration once per week for 4 weeks (2 mg/kg/week, i.p.). CAPE was administered at 10 or 20 μmol/kg/day, i.p., 5 days per week for 4 weeks. Morris water maze (MWM) and passive avoidance tests were used to assess learning and memory functions. Oxidative stress was evaluated via the colorimetric determination of GSH and MDA levels in both hippocampal and prefrontal cortex brain regions. However, inflammatory markers, acetylcholine levels, and neuronal cell apoptosis were assessed in the same brain areas using immunoassays including either ELISA, western blotting or immunohistochemistry. DOX produced significant impairment in learning and memory as indicated by the data generated from MWM and step-through passive avoidance tests. Additionally DOX-triggered oxidative stress as evidenced from the reduction in GSH levels and increased lipid peroxidation. Treatment with DOX resulted in neuroinflammation as indicated by the increase in NF-kB (p65) nuclear translocation in addition to boosting the levels of pro-inflammatory mediators (COX-II/TNF-α) along with the increased levels of glial fibrillary acid protein (GFAP) in the tested tissues. Moreover, DOX reduced acetylcholine levels and augmented neuronal cell apoptosis as supported by the increased active caspase-3 levels. Co-treatment with CAPE significantly counteracted DOX-induced behavioral and molecular abnormalities in rat brain tissues. Our results provide the first preclinical evidence for CAPE promising neuroprotective activity against DOX-induced neurodegeneration and memory deficits.

An Overview on Chemotherapy-induced Cognitive Impairment and Potential Role of Antidepressants.

Background Cognitive impairment is an adverse reaction of cancer chemotherapy and is likely to affect up to 75% of patients during the treatment and 35% of patients experience it for several months after the chemotherapy. Patients manifest symptoms like alteration in working ability, awareness, concentration, visual-verbal memory, attention, executive functions, processing speed, fatigue and behavioural dysfunctions. Post-chemotherapy, cancer survivors have a reduced quality of life due to the symptoms of chemobrain. Apart from this, there are clinical reports which also associate mood disorders, vascular complications, and seizures in some cases. Therefore, the quality of lifestyle of cancer patients/ survivors is severely affected and only worsens due to the absence of any efficacious treatments. With the increase in survivorship, it’s vital to identify effective strategies, until then only symptomatic relief for chemobrain can be provided. The depressive symptoms were causally linked to the pathophysiological imbalance between the pro and anti-inflammatory cytokines.Conclusion The common causative factor, cytokines can be targeted for the amelioration of an associated symptom of both depression and chemotherapy. Thus, antidepressants can have a beneficial effect on chemotherapy-induced inflammation and cognitive dysfunction via cytokine balance. Also, neurogenesis property of certain antidepressant drugs rationalises their evaluation against CICI. This review briefly glances upon chemotherapy-induced cognitive impairment (CICI), and the modulatory effect of antidepressants on CICI pathomechanisms.

Altered Functional Connectivity Density in Young Survivors of Acute Lymphoblastic Leukemia Using Resting-State fMRI.

ObjectiveUsing functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients.MethodsTwenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients.ResultsThe group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A.ConclusionOur results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.

Effects of a mindfulness‐based intervention on cancer‐related cognitive impairment: Results of a randomized controlled functional magnetic resonance imaging pilot study

Many breast cancer survivors suffer from cognitive complaints after cancer treatment, affecting their quality of life. The objective of this pilot study was to investigate the effect of a blended-care mindfulness-based intervention (MBI) on chemotherapy-related cognitive impairment and functional brain changes. Furthermore, correlations between changes in cognitive functioning and self-reported behavioral factors were investigated. Breast cancer survivors (n=33) who reported cognitive impairment were randomly allocated to a mindfulness condition (n=18) or a waitlist control condition (n=15). Patients completed questionnaires on cognitive impairment, emotional distress, and fatigue; neuropsychological tests; and resting-state functional magnetic resonance imaging before the start of MBI (time 1 [T1]), immediately after the completion of an 8-week MBI program (T2), and 3 months postintervention (T3). Resting-state functional connectivity was estimated in the default mode network, the dorsal and salience attention networks, and the frontoparietal network. Mixed model repeated-measures analysis was performed to test the intervention effect. Patients in the mindfulness condition exhibited significantly higher connectivity between the dorsal and salience attention networks after the mindfulness intervention compared with those in the control condition. MBI participants also had reduced subjective cognitive impairment, emotional distress, and fatigue. No intervention effect was observed on neurocognitive tests. MBI may induce functional brain changes in networks related to attention and may have a positive effect on subjective measures of cognitive impairment in breast cancer survivors. Therefore, MBI could be a suitable intervention to improve quality of life in this population and deserves further study in this context.

Pathogenesis, Assessments, and Management of Chemotherapy-Related Cognitive Impairment (CRCI): An Updated Literature Review.

There are various cancer treatments at present, and chemotherapy is one of the main methods. Chemotherapy-related cognitive impairment (CRCI), as one of the side effects of chemotherapy, has gradually attracted the attention of more and more researchers. CRCI has been verified by subjective reports and objective neuropsychological tests so far. But oncologists' understanding of it and its treatments are still incomplete. In this review, we mainly give a comprehensive overview of the mechanism of CRCI, then describe a variety of evaluation methods, and finally summarize the treatment approaches under current medical conditions and compare it with an excellent article published in 2015 with the aim of providing directions for future research and better understanding of CRCI for clinicians.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Polydatin ameliorates chemotherapy-induced cognitive impairment (chemobrain) by inhibiting oxidative stress, inflammatory response, and apoptosis in rats.

Most breast cancer survivors receiving chemotherapy have severe cognitive impairment, often referred to as "chemobrain." Polydatin (PLD) is known to have many biological activities. Thus, this study aimed to determine whether symptoms of chemobrain can be prevented or relieved by PLD. The chemobrain models were established by intraperitoneal injection of doxorubicin (DOX, 2 mg/kg) in rats once a week for 4 weeks (DOX group and DOX+PLD group). In the PLD group and DOX+PLD group, PLD (50 mg/kg) was administered orally to rats every day. We found that PLD treatment significantly protected against DOX-induced learning and memory impairment, restored hippocampal histopathological architecture. Furthermore, PLD suppressed DOX-induced oxidative stress through up-regulating Nrf2, inhibited inflammatory response by activating the NF-κB pathway, and reduced hippocampal apoptosis. Therefore, the present study indicated that PLD offered neuroprotection against DOX-induced chemobrain. PLD may assist in preventing chemobrain after chemotherapy in patients with cancers.

Stem cell therapies as a therapeutic option to counter chemo brain: a negative effect of cancer treatment.

Chemo brain, a constellation of cognitive deficiencies followed by chemotherapy drugs, used to treat different types of cancers and adversely impacts the quality of life of a cancer survivor. The underlying mechanism of chemo brain remains vague, thus delaying the advancement of efficient treatments. Unfortunately, there is no US FDA approved medicine for chemo brain and often medicines considered for chemo brain are already the ones approved for other diseases. Nevertheless, researches exploring stem cell transplantation in different neurodegenerative diseases demonstrate that cellular transplantation could reverse chemotherapy-induced chemo brain. This review talks about the mechanism behind the cognitive impairments instigated by different chemotherapy drugs used in cancer treatment, and how stem cell therapy could be advantageous to overcome this disease.

Dexmedetomidine attenuates cisplatin-induced cognitive impairment by modulating miR-429-3p expression in rats

Chemotherapy-induced cognitive impairment (CICI) is widely recognized as a frequent adverse side effect following the administration of chemotherapeutic agents. This study aimed to explore the neuroprotective functions and mechanisms of microRNAs (miRNAs) mediated by dexmedetomidine (Dex) on cisplatin-induced CICI. The model rats received 5mg/kg cisplatin injections once per week for 4weeks. Dex (30μg/kg) was administered before cisplatin treatment. The protective effects of Dex were evaluated using Morris water maze, Nissl staining, and transmission electron microscopy. Dex-mediated miRNAs were screened via miRNA sequencing. The effects of Dex and key miRNAs on mitochondrial DNA gene mt-ND1 and caspase-9 expression were tested. Dex exhibited a protective effect against decreased learning memory ability, hippocampal neuronal damage, and mitochondrial damage in CICI rats. Thirty-nine differentially expressed (DE) miRNAs were screened, 13 of which responded positively to Dex treatment. Gene Ontology annotation identified that DE miRNAs were mainly involved in transcription, DNA-templated. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DE miRNAs were mainly involved in neuronal function and brain development-related pathways, such as axon guidance and calcium signaling pathways. Compared to cisplatin treatment, the expression of miR-429-3p responded more strongly to Dex treatment. In cisplatin-treated cultured hippocampal neurons, Dex treatment and miR-429-3p overexpression significantly increased mitochondrial DNA gene mt-ND1expression and decreased caspase-9 expression. Our study suggests that Dex alleviates CICI by modulating miR-429-3p expression in rats. Thus, Dex may be effective in preventing the side effects of cisplatin.

Connectome analysis of brain functional network alterations in breast cancer survivors with and without chemotherapy

PurposeTreatment modalities for breast cancer, the leading cause of cancer-related deaths in women worldwide, include surgery, radiotherapy, adjuvant chemotherapy, targeted therapy, and hormonal therapy. The advancement in medical technology has facilitated substantial reduction in breast cancer mortality. However, patients may experience cognitive impairment after chemotherapy. This phenomenon called chemotherapy-induced cognitive impairment (i.e., “chemobrain”) is common among breast cancer survivors. However, cognitive function deficits may exist before chemotherapy initiation. This study examined the functional network alterations in breast survivors by using resting-state functional magnetic resonance imaging (fMRI).MethodsWe recruited 172 female participants and separated them into three groups: C+ (57 breast cancer survivors who had finished 3–12-month-long chemotherapy), C- (45 breast cancer survivors who had not undergone chemotherapy), and HC (70 participants with no breast cancer history). We analyzed mean fractional amplitudes of low-frequency fluctuation and graph theoretical topologies from resting-state fMRI and applied network-based analysis to portray functional changes among the three groups.ResultsAmong the three groups, the C- group demonstrated hyperactivity in the prefrontal cortex, bilateral middle temporal gyrus, right inferior temporal gyrus and right angular gyrus. Only the left caudate demonstrated significantly more hypoactivity in the C- group than in the C+ group. Graph theoretical analysis demonstrated that the brains of the C+ group became inclined toward regular networks and the brains of the C- group became inclined toward random networks.ConclusionSubtle alterations were noted in the brain activity and networks of our cancer survivors. Moreover, functional network disruptions occurred regardless of chemotherapeutic agent administration.

Therapies for cognitive impairment in breast cancer survivors treated with chemotherapy: A protocol for systematic review.

Objective:The aim of this systematic review was to evaluate the effect of therapies for cognitive impairment on patients’ perceived cognitive function in breast cancer survivors with chemotherapy-related cognitive impairment.Method:A literature search of PubMed, Embase, and the Cochrane Library was conducted up to April 2019. Search terms included breast cancer, chemotherapy, and cognitive impairment.Result:Six randomized controlled trials with a total of 305 patients were included in this review. A total of 6 randomized controlled trials using various treatments (Tibetan sound meditation, donepezil, memory and attention adaptation training, aerobic exercise, acupuncture, Qigong) for chemotherapy-related cognitive impairment met the eligibility criteria and were included. This review showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may partially improve some aspects of patients’ perceived (self-reported) cognitive functioning, particularly patients’ perceived cognitive impairment and ability.Conclusion:In this systematic review, the results showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may be optional therapies. We hope to have more randomized controlled trials to support this result in the future.

Chemotherapy-related cognitive impairment in patients with breast cancer based on MRS and DTI analysis.

The purpose of this study is to investigate chemotherapy-related cognitive impairment (CRCI) in breast cancer patients, analyze absolute concentration and structural changes of metabolites in different brain regions by multimodal neuroimaging technology, and explore correlation between them. Breast cancer patients with chemotherapy treatment group (Ctx+, N = 24) and control group without treatment (Ctx-, N = 20) underwent neuropsychological tests, multivoxel magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before and after chemotherapy. Regions of interest (ROls) in magnetic resonance scan include bilateral posterior cingulate gyrus (PCG), bilateral dorsal thalamus (DT), bilateral lenticular nucleus (LN), bilateral posterior horn of the lateral ventricle paratrigonal white matter (PWM). In MRS, absolute concentrations of N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), total creatine (tCr), glutamine + glutamate (Glx) were quantified using LC Model and SAGE software. In DTI, we used fractional anisotropy (FA) and mean diffusivity (MD) to reflect white matter integrity. In Ctx+ patients, scores of functional assessment of cancer treatment cognition test (FACT-Cog), perceived cognitive impairments (PCI), impact of perceived impairments on quality of life (QOL), perceived cognitive abilities (PCA), auditory-verbal learning test (AVLT) recognition and clock drawing test (CDT) were lower than those before chemotherapy (p < 0.05). In MRS, Ctx+ patients had significantly lower NAA values in bilateral PCG, DT, respectively. The concentrations of tCr were observed to decline in bilateral PCG and right DT. Glx values decreased in right DT. Cho values decreased significantly in bilateral DT. In DTI, Ctx+ patients had lower FA values in bilateral PCG compared with patients before chemotherapy. Among imaging metrics and cognitive scores, positive correlations were observed between changes in AVLT recognition scores and changes in NAA values in bilateral PCG (left PCG: r = 0.470, p < 0.01; right PCG: r = 0.500, p < 0.01). Positive correlations were also found between changes in AVLT recognition and changes in FA values in bilateral PCG (left PCG: r = 0.513, p < 0.01; right PCG: r = 0.563, p < 0.01). Chemotherapy can lead to a decrease in memory function, accompanied by changes in brain metabolite concentration and white matter integrity in some parts of brain.

Electroacupuncture trigeminal nerve stimulation plus body acupuncture for chemotherapy-induced cognitive impairment in breast cancer patients: An assessor-participant blinded, randomized controlled trial

Chemotherapy causes various side effects, including cognitive impairment, known as ‘chemobrain’. In this study, we determined whether a novel acupuncture mode called electroacupuncture trigeminal nerve stimulation plus body acupuncture (EA/TNS + BA) could produce better outcomes than minimum acupuncture stimulation (MAS) as controls in treating chemobrain and other symptoms in breast cancer patients. In this assessor- and participant-blinded, randomized controlled trial, 93 breast cancer patients under or post chemotherapy were randomly assigned to EA/TNS + BA (n = 46) and MAS (n = 47) for 2 sessions per week over 8 weeks. The Montreal Cognitive Assessment (MoCA) served as the primary outcome. Digit span test was the secondary outcomes for attentional function and working memory. The quality of life and multiple functional assessments were also evaluated. EA/TNS + BA treated group had much better performance than MAS-treated group on reverse digit span test at Week 2 and Week 8, with medium effect sizes of 0.53 and 0.48, respectively, although no significant differences were observed in MoCA score and prevalence of chemobrain between the two groups. EA/TNS + BA also markedly reduced incidences of diarrhoea, poor appetite, headache, anxiety, and irritation, and improved social/family and emotional wellbeing compared to MAS. These results suggest that EA/TNS + BA may have particular benefits in reducing chemotherapy-induced working memory impairment and the incidence of certain digestive, neurological, and distress-related symptoms. It could serve as an effective intervention for breast cancer patients under and post chemotherapy (trial registration: https://www.clinicaltrials.gov: NCT02457039).

Falls and Cancer

Falls among older people are common and are associated with substantial morbidity, mortality and healthcare costs. Increasingly cancer is becoming a disease of older people and fall rates are higher in elders living with cancer. Cancer and its treatments potentiate important risk factors for falls, including muscle weakness, poor balance, proprioception, cognitive impairment and functional disability. Sarcopenia refers to the progressive deterioration in muscle strength, mass and quality with ageing. Chronic conditions and cancer amplify this decline and are associated with a greater negative effect on function. Age-related impairments of lower limb neurological function are commonly exacerbated by neurotoxic chemotherapy, resulting in gait and balance deficits. Postural instability and falls erode confidence and result in a negative cycle of diminishing activity levels, further deconditioning and a higher risk of further falls. Cancer-related fatigue, sleep and mood disturbances compound this progressive frailty, further worsening treatment tolerance and outcomes. Cognitive impairment is a potent risk factor for falling and is frequently associated with gait abnormalities. The well-recognised effects of cancer treatment on working memory, attention, processing speed and executive function are often apparent (when their presence is sought) before treatment and may be as much the result of the cancer itself as they are ‘chemo brain’. Structured exercise programmes focusing on progressively challenging strength and balance training are of proven benefit in falls prevention. Regular aerobic exercise accrues additional benefits in improved cardiorespiratory resilience and concomitant positive effects on treatment tolerance. Increased activity levels positively influence cognition, mood and foster an improved sense of well-being. Simple, practicable clinic-based tests of physical functioning, cognition and neurological function can help to identify those at high risk of falls and functional decline. The use of such instruments can aid judicious treatment planning and identify those most likely to benefit from more detailed specialist comprehensive geriatric assessment.

Neuropsychological functioning among patients with different types of cancer : Postchemotherapy cognitive impairment and implications for rehabilitation.

Chemotherapeutic drugs often contribute to the cognitive impairment observed in some individuals following chemotherapy treatment. Postchemotherapy cognitive impairment (PCCI) is referred to as adecline in avariety of neuropsychological measures after chemotherapy and has an acute onset. The goals of the present study are to compare the manifestation of longitudinal PCCI among 182 patients with four different types of cancer (breast, colorectal, prostate and thyroid cancer) before chemotherapy (T1), immediately after chemotherapy (T2) and 6months later (T3). Although no statistically significant differences were observed between the study groups in any of the cognitive domains before chemotherapy, patients with breast cancer showed significantly lower performance on all cognitive domains compared to other patients at the postchemotherapy timepoints. Although cognitive difficulties are reported during and after chemotherapy for cancer, it seems that there are differences between different types of cancer. We conclude that it is particularly important to assess and manage these cognitive disorders. Management includes rehabilitation programs that can improve cognitive functions and contribute to changes in brain functions to facilitate this improvement.

Long-term clinically relevant rodent model of methotrexate-induced cognitive impairment.

With the enhanced use of chemotherapy and the advent of increased patient survival rates, there are an increasing number of cancer survivors living with chemotherapy-induced cognitive impairment. A growing number of clinical studies have brought to light the association of agents like methotrexate in generating these neurological sequelae, although mechanisms remain unclear. Here, we use a clinically relevant regimen of several cycles of methotrexate and leucovorin rescue to develop a model of chemotherapy-induced cognitive impairment, and investigate the in vivo long-term (16 mo) impact of high-dose systemic methotrexate on white matter cellular dynamics as assessed by stereology, animal behavior, and diffusion tensor imaging. Our results indicate that at 6 and 16 months post-chemotherapy, methotrexate-treated rats exhibit a significant and permanent decrease in the number of oligodendrocytes and their progenitors in the white matter, in corpus callosum volumes, and myelin basic protein. These findings are associated with mostly delayed deficits in performance on Morris Water Maze and Novel Object Recognition tasks. Diffusion tensor imaging demonstrates significantly decreased fractional anisotropy values in the callosum genu, body, and splenium, as well as previously unassessed areas like the fimbria. Interestingly, these white matter changes are preceded by an earlier, transient decrement in white matter microglia at 3 months, and hippocampal neural progenitors at 3 and 6 months. These results demonstrate a significant negative impact of methotrexate on the oligodendrocyte compartment and white matter, associated with cognitive impairment. The data also support the use of diffusion tensor imaging in monitoring white matter integrity in this context.

Oroxylum indicum extract prevents chemotherapy‐induced cognitive impairment in mice

Chemotherapy‐induced cognitive impairment (CICI) is an emerging concern among cancer patients undergoing chemotherapy treatment. Several mechanisms including neuronal oxidative stress and mitochondrial dysfunction have been proposed as the underlying mechanisms of CICI. While a few synthetic and natural compounds with different mechanisms of action have been proposed for targeting the CICI, their beneficial effects are outweighed by severe adverse effects including reduced efficacy of chemotherapy drugs. Therefore, search for novel and safer neuroprotective avenues to target CICI is needed. We sought to determine whether Oroxylum indicum extract (OIE, Sabroxy®) prevents CICI in a rodent model by suppressing chemotherapy induced neuronal oxidative stress and mitochondrial dysfunction. Male C57BL/6J mice were injected intraperitoneally with saline or doxorubicin (2mg/kg) and cyclophosphamide (50mg/kg) once a week for 4 weeks. While control mice received powdered rodent food alone, OIE treatment group received the powdered rodent food mixed with OIE (250 or 500mg/kg) daily for 4 weeks. After the treatment period, the mice were assessed for cognitive function using novel object recognition, Y‐maze, and Morris water maze analyses. Biochemical assays were performed using brain tissues to determine the underlying mechanisms of CICI. While the chemotherapy treatment impaired the performance of the mice in the novel object recognition, Y‐maze and Morris water maze tests, OIE significantly prevented the chemotherapy impaired performance in these tests. Additionally, OIE treatment prevented the chemotherapy‐induced changes in oxidative stress and mitochondrial dysfunction in the cortex and rest of the brain. Mechanistically, OIE enhanced mitochondrial function and counteracted chemotherapy‐increased reactive oxygen species formation and lipid peroxidation. Furthermore, OIE treatment increased the monoamine oxidase activity in the cortex and rest of the brain. Our results support the hypothesis that neuronal mitochondrial dysfunction induced by doxorubicin and cyclophosphamide treatment is an underlying cause of CICI, and that OIE may be offered as an adjuvant therapeutic strategy to treat CICI.Support or Funding InformationOIE (Sabroxy®) and funding was provided by Sabinsa Corporation.