Cancer-related cognitive impairment: updates to treatment, the need for more evidence, and impact on quality of life-a narrative review.

BACKGROUND AND OBJECTIVE: Due to advances in early detection and treatment options, non-central nervous system (non-CNS) cancer survivors are living longer, even those with metastatic disease. Many of these survivors will experience enduring symptoms of breast cancer, such as cancer-related cognitive impairment (CRCI). Although CRCI is bothersome and, in some cases, potentially debilitating, little research has been done to address this symptom. Thus, the overarching goal of this narrative review is to provide both an overview of the problem of CRCI and its impact and focus on the latest research aimed at addressing CRCI in non-CNS cancer survivors. METHODS: A MEDLINE database (PubMed) search was conducted for terms related to non-CNS cancer, cognition, impacts of CRCI, and interventions. The English-language articles published until April 8th, 2024, were included in the search. KEY CONTENT AND FINDINGS: CRCI includes self-reported cognitive complaints and/or impaired performance in multiple cognitive domains, including memory, processing speed, attention, and executive function. CRCI, in turn, can have a significant impact on everyday functioning, work ability, work engagement and productivity, and overall quality of life (QoL) of cancer survivors. While some researchers have examined pharmacological approaches, the vast majority of the interventional studies to date to address CRCI has focused on non-pharmacological approaches. Three of the most common non-pharmacological approaches are physical activity or exercise, mind-body approaches [e.g., mindfulness-based stress reduction (MBSR)], and cognitive rehabilitative approaches [e.g., cognitive training (CT) and cognitive behavioral therapy (CBT)]. CONCLUSIONS: Addressing the cognitive health of cancer survivors is imperative but has only recently been the focus of interventional research. More research in larger and more diverse samples of non-CNS cancer survivors is needed to identify effective ways to manage CRCI for all cancer survivors. Overall, maintaining cognitive health, especially in cancer survivors who are at increased risk for deficits, is a national health care priority that should not be ignored.

It's about time: mitigating cancer-related cognitive impairments through findings from computational models of the Wisconsin Card Sorting Task.

BACKGROUND: Many cancer survivors experience cancer-related cognitive impairment (CRCI), often with significant negative consequences across various life domains. Emerging evidence suggests that allowing additional time to process information before acting may be a useful strategy for those with CRCI to mitigate some of its impacts. The Wisconsin Card Sorting Task (WCST), a measure of general cognition, has shown that for some cancer survivors, longer task completion time facilitates similar task performance outcomes to control populations concerning perseveration errors; a key performance metric of the WCST. However, assessing if this strategy may be useful, as well as determining for whom it may be useful, with regard to strengths and weaknesses among select cognitive domains, is challenging due to factors such as the problem of task impurity. Accordingly, this study provides an initial computational and experimental assessment of whether additional time to process information before acting is a useful strategy for those with CRCI. METHODS: We simulated individual cognitive differences observed in humans by varying contributions of executive functioning components (updating, shifting, inhibition) to yield 48 distinct computational models of the WCST. Our main manipulation was then to provide these models with more or less time (at three levels of 20, 40 and 60 cycles) before models executed an action to sort a given card. We compared the number of perseveration errors on the WCST produced by the computational models. Additionally, we determined models that simulated the performance of cancer survivors on the WCST by comparing the number of perseveration errors produced by the models to human data. RESULTS: Additional processing time resulted in the models producing significantly fewer perseveration errors, supporting our hypothesis. In addition, 8 unique models simulated the performance of cancer survivors on the WCST. Additional time appeared to have a positive influence on performance primarily by mitigating the impacts of severe inhibition impairments. For more severe global executive function impairments, a substantial amount of additional time was required to mitigate the impacts of the impairments. For the most severe impairments, additional time was unable to adequately mitigate the impact on performance. CONCLUSION: Additional processing time may be a useful strategy to rectify perseveration errors among cancer survivors with CRCI. Our findings have implications for the development of practical strategies, such as workload and deadline management in occupational settings, which may mitigate the negative effects of CRCI.

Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice.

Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with 20 Gy or 30 Gy to induce subclinical or clinical dermatitis, respectively. Mice were euthanized at 6 h, 24 h, 5 days, 12 days, and 25 days post irradiation, and the brain, thoracic spinal cord, and skin were collected. The brains were harvested for spatial proteomics, immunohistochemistry, Nanostring nCounter® glial profiling, and neuroinflammation gene panels. The thoracic spinal cords were evaluated by immunohistochemistry. Radiation injury to the skin was evaluated by histology. The genes associated with neurotransmission, glial cell activation, innate immune signaling, cell signal transduction, and cancer were differentially expressed in the brains from mice treated with ECRT compared to the controls. Dose-dependent increases in neuroinflammatory-associated and neurodegenerative-disease-associated proteins were measured in the brains from ECRT-treated mice. Histologic changes in the ECRT-treated mice included acute dermatitis within the irradiated skin of the hindlimb and astrocyte activation within the thoracic spinal cord. Collectively, these findings highlight indirect neuronal transmission and glial cell activation in the pathogenesis of ECRT-related CRCI, providing possible signaling pathways for mitigation strategies.

Cancer related cognitive impairment: a downside of cancer treatment.

Cancer treatment is associated with long lasting cognitive impairment in cancer survivors. This cognitive impairment is often termed cancer related cognitive impairment (CRCI). Cancer survivors treated for tumors outside the central nervous system are increasingly diagnosed with CRCI. The development of strategies to mitigate the negative effects of cancer treatment on the brain are crucial. Although neuroimaging research has proposed several candidate mechanisms, the pathogenic underpinnings of CRCI remain uncertain. As such, preventative and treatment strategies have not been identified. To fill these gaps, animal models play a vital role in isolating underlying contributing mechanisms that promote CRCI and in testing new therapeutic approaches.

Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity.

Cancer-related cognitive impairments (CRCI) are neurological complications associated with cancer treatment, and greatly affect cancer survivors' quality of life. Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis, learning and memory. The reduction of BDNF is associated with the decrease in cognitive function in various neurological disorders. Few pre-clinical studies have reported on the effects of chemotherapy and medical stress on BDNF levels and cognition. The present study aimed to compare the effects of medical stress and cisplatin on serum BDNF levels and cognitive function in 9-month-old female Sprague Dawley rats to age-matched controls. Serum BDNF levels were collected longitudinally during cisplatin treatment, and cognitive function was assessed by novel object recognition (NOR) 14 weeks post-cisplatin initiation. Terminal BDNF levels were collected 24 weeks after cisplatin initiation. In cultured hippocampal neurons, we screened three neuroprotective agents, riluzole (an approved treatment for amyotrophic lateral sclerosis), as well as the ampakines CX546 and CX1739. We assessed dendritic arborization by Sholl analysis and dendritic spine density by quantifying postsynaptic density-95 (PSD-95) puncta. Cisplatin and exposure to medical stress reduced serum BDNF levels and impaired object discrimination in NOR compared to age-matched controls. Pharmacological BDNF augmentation protected neurons against cisplatin-induced reductions in dendritic branching and PSD-95. Ampakines (CX546 and CX1739) and riluzole did not affect the antitumor efficacy of cisplatin in vitro. In conclusion, we established the first middle-aged rat model of cisplatin-induced CRCI, assessing the contribution of medical stress and longitudinal changes in BDNF levels on cognitive function, although future studies are warranted to assess the efficacy of BDNF enhancement in vivo on synaptic plasticity. Collectively, our results indicate that cancer treatment exerts long-lasting changes in BDNF levels, and support BDNF enhancement as a potential preventative approach to target CRCI with therapeutics that are FDA approved and/or in clinical study for other indications.

Elucidating the relationship between breast cancer and brain cortical structure: a Mendelian randomization study.

Cancer-associated cognitive impairment is a significant challenge for individuals who have survived breast cancer, affecting their quality of life. In this study, we conducted an inaugural comprehensive Mendelian randomization analysis discerning the causal relationship between breast cancer, including its two subtypes, and the cerebral cortical structure. Our analysis indicated that estrogen receptor-negative breast cancer significantly decreased surface area (ß = -593.01 mm2, 95% CI: -1134.9 to -51.1 mm2, P = 0.032). At the regional level, estrogen receptor-negative breast cancer showed a significant association with surface area and thickness in 17 cortical regions. These regions included the insula, posterior cingulate, superior frontal, precuneus, fusiform, lateral occipital, and rostral middle frontal. Specifically, estrogen receptor-negative breast cancer had a significant impact on decreasing the surface area of the insula without considering global weight (ß = -14.09 mm2, 95% CI: -22.91 to -5.27 mm2, P = 0.0017). The results from meta-analysis and LD Score Regression provide support for our findings. This investigation unveils the correlations between breast cancer, its various subcategories, and the cerebral cortical structure. Notably, breast cancer of the estrogen receptor-negative variety may elicit more widespread cerebral atrophy.

Effects of exercise on cancer-related cognitive impairment in breast cancer survivors: a scoping review.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is one of the major long-term concerns reported by breast cancer survivors after overcoming the disease. The present study undertakes a scoping review of relevant research publications to explore the effect of increasing physical activity (PA) levels or the use of exercise (EX)-based programs on CRCI in female breast cancer survivors; who have completed neo/adjuvant chemotherapy treatment and are awaiting or receiving hormonal therapy. METHODS: An electronic search of Pubmed, Embase, Scopus, WOS, and Cochrane databases has been conducted to identify published literature from January 2000 to December 2021. RESULTS: Of 1129 articles, twenty met the inclusion criteria. The majority of the included observational studies (90%) reported cross-sectional design; meanwhile, 72% of experimental research reported randomized controlled trials (RCTs) or randomized crossover trials. 15 neuropsychological batteries and tests, and 5 self-reported validated questionnaires were employed. Only 27% of the included articles used a combination of the previously mentioned methods. The recorder of moderate-vigorous PA (MVPA), defined as more than 3 METs, or represented as average daily minutes spent (≥ 1952 counts/min) was the most analyzed variable in cross-sectional studies, and EX programs based on aerobic training (AT) were the most proposed by RCTs. CONCLUSIONS: The exploratory approach of this review demonstrates modest but increasingly promising evidence regarding exercise's potential to improve brain health among breast cancer survivors although these findings highlight the importance of addressing methodological heterogeneity in the same direction with the view of using exercise within the clinic area.

Managing Cancer and Living Meaningfully (CALM) alleviates chemotherapy related cognitive impairment (CRCI) in breast cancer survivors: A pilot study based on resting-state fMRI.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) is a type of memory and cognitive impairment induced by chemotherapy and has become a growing clinical problem. Breast cancer survivors (BCs) refer to patients from the moment of breast cancer diagnosis to the end of their lives. Managing Cancer and Living Meaningfully (CALM) is a convenient and easy-to-apply psychological intervention that has been proven to improve quality of life and alleviate CRCI in BCs. However, the underlying neurobiological mechanisms remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) has become an effective method for understanding the neurobiological mechanisms of brain networks in CRCI. The fractional amplitude of low-frequency fluctuations (fALFF) and ALFF have often been used in analyzing the power and intensity of spontaneous regional resting state neural activity. METHODS: The recruited BCs were randomly divided into the CALM group and the care as usual (CAU) group. All BCs were evaluated by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) before and after CALM or CAU. The rs-fMRI imaging was acquired before and after CALM intervention in CALM group BCs. The BCs were defined as before CALM intervention (BCI) group and after CALM intervention (ACI) group. RESULTS: There were 32 BCs in CALM group and 35 BCs in CAU group completed the overall study. There were significant differences between the BCI group and the ACI group in the FACT-Cog-PCI scores. Compared with the BCI group, the ACI group showed lower fALFF signal in the left medial frontal gyrus and right sub-gyral and higher fALFF in the left occipital_sup and middle occipital gyrus. There was a significant positive correlation between hippocampal ALFF value and FACT-Cog-PCI scores. CONCLUSIONS: CALM intervention may have an effective function in alleviating CRCI of BCs. The altered local synchronization and regional brain activity may be correlated with the improved cognitive function of BCs who received the CALM intervention. The ALFF value of hippocampus seems to be an important factor in reflect cognitive function in BCs with CRCI and the neural network mechanism of CALM intervention deserves further exploration to promote its application.

Advances of neuroimaging in chemotherapy related cognitive impairment (CRCI) of patients with breast cancer.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) has seriously affected the quality of life (QOL) of patients with breast cancer (BCs), thus the neurobiological mechanism of CRCI attracted widespread attention. Previous studies have found that chemotherapy causes CRCI through affecting brain structure, function, metabolism, and blood perfusion. FINDINGS: A variety of neuroimaging techniques such as functional magnetic resonance imaging (fMRI), event-related potential (ERP), near-infrared spectroscopy (NIRS) have been widely applied to explore the neurobiological mechanism of CRCI. CONCLUSION: This review summarized the progress of neuroimaging research in BCs with CRCI, which provides a theoretical basis for further exploration of CRCI mechanism, disease diagnosis and symptom intervention in the future. Multiple neuroimaging techniques for CRCI research.

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

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

Brain network deficits in breast cancer patients after early neoadjuvant chemotherapy: A longitudinal MRI study.

Breast cancer (BC) patients who undergo chemotherapy are likely to develop chemotherapy-related cognitive impairment (CRCI). Recent studies of BC patients after chemotherapy have used graph theory to investigate the topological properties of the brain functional connectome. However, little is known about structural morphological networks in BC patients after early neoadjuvant chemotherapy (NAC). Brain morphological network organization in 47 female participants with BC was investigated before and after NAC. Topological properties of brain networks were ascertained based on morphological similarities in regional gray matter using a graph theory approach based on 3D T1-weighted MRI data. Nonparametric permutation testing was used to assess longitudinal-group differences in topological metrics. Compared with BC patients before NAC, BC patients after early NAC showed significantly increased global efficiency (p = .048), decreased path length (p = .033), and abnormal nodal properties and connectivity, mainly located in the central executive network (CEN). The change in the network efficiency of the right caudate was negatively correlated with the change in the Self-Rating Anxiety Scale score (r = -.435, p = .008), and the change in the nodal degree of the left superior frontal gyrus (dorsolateral part) was positively correlated with the change in the Functional Assessment of Cancer Therapy score (r = .547, p = .002). BC participants showed randomization in global properties and dysconnectivity in the CEN after early NAC. NAC may disrupt the cognitive balance of the brain morphological network in individuals with BC.

The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

BACKGROUND: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated. METHODS: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values. RESULTS: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training. CONCLUSION: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy-related cognitive impairment in patients with breast cancer who receive chemotherapy.

BACKGROUND: Chemotherapy-related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI. METHODS: This study enrolled one hundred and twenty-four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single-nucleotide polymorphisms (SNP) to explore these. The mini-mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT). RESULTS: We found that patients with ALDH2 gene genotypes of rs671_GG, rs886205_GG, rs4648328_CC, and rs4767944_TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671_GG of DST (z = 2.769, p = 0.006), VFT (t = 4.624, P<0.001); rs886205_GG of DST (z = 3.663, P<0.001); rs4648328_CC of DST (z = 2.850, p = 0.004), VFT (t = 3.477, p = 0.001); and rs4767944_TT of DST (z = 2.967, p = 0.003), VFT (t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious. CONCLUSION: Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single-nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians.

The Distant Molecular Effects on the Brain by Cancer Treatment.

Cancer survivors experience cancer-related cognitive impairment (CRCI) secondary to treatment. Chemotherapy and radiation therapy independently contribute to cognitive dysfunction; however, the underlying mechanisms leading to dysfunction remain unclear. We characterized brain gene expression changes in a mouse model of CRCI to identify the mechanistic underpinnings. Eleven-to-twelve-week-old SKH1 mice were treated with doxorubicin (DOX), hindlimb radiation (RT), concurrent hindlimb radiation and doxorubicin (DOX-RT), or no treatment (control). Sixteen days following treatment, gene expression was measured from murine brains using the NanoString nCounter® glial profiling panel. Gene expression was normalized and compared between groups. No two groups shared the same expression pattern, and only Gnb1 and Srpr were upregulated in multiple treatment groups. Brains from DOX-treated mice had upregulated Atf2, Atp5b, Gnb1, Rad23b, and Srpr and downregulated Sirt5 expression compared to control brains. Brains from RT-treated mice demonstrated increased Abcg2 and Fgf2 and decreased C1qa and C1qb expression compared to control brains. Brains from DOX-RT-treated mice had upregulated Adar, E2f3, Erlec1, Gnb1, Srpr, Vim, and Pdgfra expression and downregulated Rock2 and Inpp5f expression compared to control brains. The gene expression changes demonstrated here highlight roles for neuronal transmission and oxidative stress in the pathogenesis of doxorubicin-related CRCI and inflammation in RT-related CRCI.

The Managing Cancer and Living Meaningfully (CALM) Intervention Alleviates Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer by Modulating Pan-Immune-Inflammation Values.

BACKGROUND: The number of patients with breast cancer is increasing worldwide, resulting in a growing number of patients with chemotherapy-related cognitive impairment (CRCI), which seriously affects their quality of life. CRCI is associated with inflammatory factors and systemic inflammatory markers such as pan-immune-inflammation value (PIV) and monocyte-to-lymphocyte ratio (MLR), which can reflect the level of inflammation in the body. While the Managing Cancer and Living Meaningfully (CALM) intervention has been demonstrated to alleviate CRCI in patients with breast cancer, the specific mechanism remains unclear. OBJECTIVE: This study evaluated the impact of the CALM intervention on systemic inflammation. METHODS: Ninety patients with breast cancer with CRCI were enrolled and randomized into care as usual (CAU) and CALM intervention groups. All patients were assessed using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Mini-Mental State Exam (MMSE), and Functional Assessment of Cancer Therapy-Breast (FACT-B) before and after the CAU/CALM intervention. The blood levels of inflammatory markers were also analyzed before and after the intervention. RESULTS: Compared to the CAU group, the CALM group showed significantly improved cognitive function and significantly decreased PIV (P < .05). PIV was significantly negatively correlated with FACT-Cog (P < .05). The levels of other inflammatory markers, including MLR, neutrophil-to-lymphocyte ratio (NLR), granulocyte-to-lymphocyte ratio (GLR), and systemic immune-inflammation index (SII), were also reduced in the CALM group. CONCLUSION: PIV is an important marker of inflammation. The CALM intervention may improve the cognitive function of patients by regulating the systemic inflammation marker PIV through the neuroimmune axis.

Cancer-related cognitive impairment in non-CNS cancer patients: Targeted review and future action plans in Europe.

Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs.

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

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

Mini-review: Aplastic myelin following chemotherapy.

The contribution of chemotherapy to improved outcomes for cancer patients is unquestionable. Yet as its applications broaden, so do the concerns for the long-term implications of chemotherapy on the health of cancer survivors, with chemotherapy-related cognitive impairment as a cause for particular urgency. In this mini review, we explore myelin aplasticity following chemotherapy, discussing the role of myelin plasticity in healthy cognition and failure of myelin plasticity chiefly due microenvironmental aberrations in chemotherapy-related cognitive impairment. Possible therapeutic strategies to mitigate chemotherapy-induced myelin dysfunction are also discussed.

Establishing construct validity of neuropsychological tests in cancer survivors.

OBJECTIVE: Cancer-related cognitive impairments (CRCI) are frequently reported among cancer survivors, and attention is the most frequently assessed cognitive domain in CRCI. However, there is no consensus as to whether attention is impaired. We suggest that a major reason for this lack of agreement is a lack of construct validity for neuropsychological attention tests. We propose to assess the construct validity of neuropsychological attention tests with respect to experimental paradigms from cognitive psychology. METHODS: Self-reported cancer survivors (N = 314) completed an online battery comprising six experimental attention paradigms and eight neuropsychological tests. Confirmatory factor analysis was used to evaluate the fit of five models derived from a general population sample (N = 636) in a previous study (M. Treviño, Cogn Res Princ Implic, in press). We then subjected the best-fitting model to a measurement invariance analysis. RESULTS: The best-fitting model was a six intercorrelated factor structure, comprising Capacity, Search, Digit Span, Arithmetic, Sustained Attention, and Flanker Interference factors. Configural and weak invariance held, indicating that the factor loadings were invariant across groups. Strong invariance, indicating that intercepts were also invariant, held except for the Approximate Number Sense test. CONCLUSIONS: According to our factor model, Spatial Span and Digit Symbol Coding measure attentional capacity, while the Trail Making Test (A&B) and Letter Cancellation tests measure visual search ability. However, Digit Span and Arithmetic tests do not measure attention. We hope that these results will lead to better scientific models, better patient education, and, ultimately, improved outcomes for survivors.