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    Cognitive Dysfunction and Its Predictors in Adult Patients With Cancer Receiving Chemotherapy: A Cross-Sectional Correlational Study. Wazqar Dhuha Youssef The journal of nursing research : JNR BACKGROUND:Chemotherapy-related cognitive dysfunction, one of the most frequently reported symptoms in patients with cancer, has a negative impact on the daily lives of patients. No research has examined cognitive dysfunction and its potential predictors in adult patients with cancer receiving chemotherapy in Saudi Arabia. PURPOSE:The purpose of this study was to examine the sociodemographic, clinical, and psychological factors associated with cognitive dysfunction in adult patients with cancer receiving chemotherapy. METHODS:A cross-sectional correlational study was carried out with a convenience sample of 100 adult patients with cancer receiving chemotherapy at a university teaching hospital in Saudi Arabia. The Montreal Cognitive Assessment, the Hospital Anxiety and Depression Scale, and sociodemographic and clinical surveys were completed by participants. Descriptive statistics and linear regression were used to analyze the data. RESULTS:The data showed that the participants experienced moderate-to-severe cognitive dysfunction. Participants performed poorly in the divided attention and memory cognitive domains. Age, educational level, and depression factors were found to be significant predictors of cognitive dysfunction. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:Cognitive dysfunction is commonly seen in patients with cancer receiving chemotherapy. Chemotherapy, age, and psychological factors increase susceptibility to cognitive dysfunction in adult patients with cancer. Oncology nurses should be aware that patients with cancer may be extremely vulnerable to cognitive dysfunction. Furthermore, age and psychological factors must be considered when developing symptom management and supportive care intervention programs to reduce the incidence of negative cognitive outcomes in this population. 10.1097/jnr.0000000000000340
    The impact of cognitive impairment on self-regulatory styles in breast cancer survivors. Becker Jacqueline H,Ezratty Charlotte,Jahan Nusrat,Goel Mita,Harris Yael Tobi,Lin Jenny J Psycho-oncology OBJECTIVE:Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS:We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS:Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS:BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes. 10.1002/pon.5633
    Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial. Yang Tong,Wang Hualou,Xiong Ying,Chen Chong,Duan Keran,Jia Jingya,Ma Fei Journal of Alzheimer's disease : JAD BACKGROUND:Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. OBJECTIVE:To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. METHODS:This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. RESULTS:Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). CONCLUSION:Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline. 10.3233/JAD-200926
    Association Between Dietary Intakes of B Vitamins in Midlife and Cognitive Impairment in Late-Life: The Singapore Chinese Health Study. Sheng Li-Ting,Jiang Yi-Wen,Pan Xiong-Fei,Feng Lei,Yuan Jian-Min,Pan An,Koh Woon-Puay The journals of gerontology. Series A, Biological sciences and medical sciences BACKGROUND:Dietary intakes of B vitamins (eg, folate) are related to cognitive function according to epidemiological studies in western countries. But prospective studies in Asian populations are scarce. This study evaluated the relationships of dietary intakes of six B vitamins in midlife with cognitive impairment in old age in a Chinese population living in Singapore. METHODS:This study included 16,948 participants from the Singapore Chinese Health Study, a population-based prospective cohort. Baseline dietary intakes of B vitamins were assessed using a validated 165-item food frequency questionnaire when the participants were aged 45-74 years (1993-1998). After an average follow-up of 20 years, cognitive function was examined using a Singapore-modified version of Mini-Mental State Examination scale in 2014-2016, and cognitive impairment was defined using education-specific cutoffs. Logistic regression models were applied to estimate the association between B vitamins and cognitive impairment. All the six B vitamins were mutually adjusted in the final model. RESULTS:In the 2014-2016 interview, 2,443 participants were defined as cognitive impairment. Riboflavin and folate were significantly and independently associated with cognitive impairment in a dose-dependent manner: the odds ratio (95% confidence interval) comparing the highest with the lowest quartile was 0.82 (0.69, 0.97) for riboflavin and 0.83 (0.70, 0.98) for folate (both p-trend <.05). Dietary intakes of thiamine, niacin, vitamin B-6, and B-12 were not significantly associated with risk of cognitive impairment. CONCLUSIONS:Higher dietary intakes of riboflavin and folate in midlife were associated with a lower risk of cognitive impairment in late-life in the Chinese population. 10.1093/gerona/glz125
    Long-Term Cognitive Dysfunction in Cancer Survivors. Országhová Zuzana,Mego Michal,Chovanec Michal Frontiers in molecular biosciences Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality of life. Different definitions and means of evaluation have been used in available literature; hence the exact incidence of CRCI remains unknown. CRCI can be described as cognitive symptoms reported by cancer patients in self-reported questionnaires or as cognitive changes evaluated by formal neuropsychological tests. Nevertheless, association between cognitive symptoms and objectively assessed cognitive changes is relatively weak or absent. Studies have focused especially on breast cancer patients, but CRCI has been reported in multiple types of cancer, including colorectal, lung, ovarian, prostate, testicular cancer and hematological malignancies. While CRCI has been associated with various treatment modalities, including radiotherapy, chemotherapy, hormone therapy and novel systemic therapies, it has been also detected prior to cancer treatment. Therefore, the effects of cancer itself with or without the psychological distress may be involved in the pathogenesis of CRCI as a result of altered coping mechanisms after cancer diagnosis. The development of CRCI is probably multifactorial and the exact mechanisms are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age and psychological factors such as anxiety, depression or fatigue. Multiple mechanisms are suggested to be responsible for CRCI, including direct neurotoxic injury of systemic treatment and radiation while other indirect contributing mechanisms are hypothesized. Chronic neuroinflammation mediated by active innate immune system, DNA-damage or endothelial dysfunction is hypothesized to be a central mechanism of CRCI pathogenesis. There is increasing evidence of potential plasma (e.g., damage associated molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, and others), cerebrospinal fluid and radiological biomarkers of cognitive dysfunction in cancer patients. Discovery of biomarkers of cognitive impairment is crucial for early identification of cancer patients at increased risk for the development of CRCI or development of treatment strategies to lower the burden of CRCI on long-term quality of life. This review summarizes current literature on CRCI with a focus on long-term effects of different cancer treatments, possible risk factors, mechanisms and promising biomarkers. 10.3389/fmolb.2021.770413
    A cognitively enhanced online Tai Ji Quan training intervention for community-dwelling older adults with mild cognitive impairment: A feasibility trial. Li Fuzhong,Harmer Peter,Fitzgerald Kathleen,Winters-Stone Kerri BMC geriatrics BACKGROUND:This study examines the feasibility, acceptability, and safety of a newly developed cognitive-enhancing Tai Ji Quan training intervention, delivered via remote videoconferencing, for older adults with mild cognitive impairment (MCI). METHODS:In a three-arm feasibility trial, community-dwelling older adults with MCI (N = 69; mean age = 74.6 years, 57% women) were randomized to a cognitively enhanced Tai Ji Quan (n = 23), standard Tai Ji Quan (n = 22), or stretching group (n = 24) and participated in a 60-minute online exercise session via Zoom, twice weekly for 16 weeks. Participants were recruited primarily in the state of Oregon through mass mailing and word of mouth. The primary outcomes were intervention feasibility (with respect to recruitment, online intervention delivery, fidelity and compliance, and attrition and retention rates), acceptability, and safety. We also assessed feasibility of online data collection and test-retest reliability and explored preliminary trends on secondary outcomes that included global cognitive function, dual-task cost, and domain-specific cognition function. RESULTS:The study had an average recruitment rate of 55%. Feasibility was demonstrated by the overall successful online program implementation, with good fidelity, acceptable compliance (76%), and excellent retention (94%). The cognitively enhanced Tai Ji Quan intervention was shown to be acceptable to participants as well as safe, with no major intervention-related moderate/severe events. At week 16, the group receiving cognitively enhanced Tai Ji Quan training showed a positive trend in the cognitive function and dual-task outcome measures whereas the group receiving standard Tai Ji Quan training exhibited positive trends on global and domain-specific cognitive measures. CONCLUSIONS:Preliminary findings of this pilot study indicate the feasibility, acceptability, and safety of a tailored, cognitively enhanced Tai Ji Quan training intervention delivered remotely to home settings via videoconferencing for community-dwelling older adults with MCI. TRIAL REGISTRATION:Clinicaltrials.gov identifier NCT04070703. 10.1186/s12877-021-02747-0
    Cancer and cancer-therapy related cognitive dysfunction: an international perspective from the Venice cognitive workshop. Vardy J,Wefel J S,Ahles T,Tannock I F,Schagen S B Annals of oncology : official journal of the European Society for Medical Oncology A subset of survivors has cognitive impairment after cancer treatment. This is generally subtle, but may be sustained. In October 2006, the second international cognitive workshop was held in Venice. The workshop included neuropsychologists, clinical and experimental psychologists, medical oncologists, imaging experts, and patient advocates. The main developments since the first Cognitive Workshop in 2003 have been the following. (i) studies evaluating cognitive function in patients receiving chemotherapy for cancers other than breast cancer, and in patients receiving hormonal therapy for cancer. (ii) The publication of longitudinal prospective studies which have shown that some patients already exhibit cognitive impairment on neuropsychological testing before receiving chemotherapy, and some patients have deterioration in cognitive functioning from pre- to postchemotherapy. (iii) Studies of the underlying mechanisms of cognitive impairment both in patients and in animal models. (iv) Use of structural and functional imaging techniques to study changes in brain morphology and activation patterns associated with chemotherapy. (v) At present cognitive research in cancer is limited by methodological challenges and the lack of standardization in neuropsychological studies. The current workshop addressed many of these issues and established an international task force to provide guidelines for future research and information on how best to manage these symptoms. 10.1093/annonc/mdm500
    Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. Wefel Jeffrey S,Kesler Shelli R,Noll Kyle R,Schagen Sanne B CA: a cancer journal for clinicians Answer questions and earn CME/CNE Over the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported-that cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case-study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed. 10.3322/caac.21258
    Effects of computerised cognitive training on cognitive impairment: a meta-analysis. Hu Mingyue,Wu Xinyin,Shu Xinhui,Hu Hengyu,Chen Qiong,Peng Linlin,Feng Hui Journal of neurology INTRODUCTION:Computerised cognitive training (CCT) has been shown to enhance cognitive function in elderly individuals with cognitive deterioration, but evidence is controversial. Additionally, whether specific CCT is most effective and which stages of cognitive impairment benefit most is unclear. METHODS:We systematically searched nine medical and technological databases to collect randomized controlled trials related to CCT primarily conducted in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). RESULTS:We identified 12 studies in patients with SCD and MCI. Pooled analysis showed that CCT could significantly improve cognitive function (g = 0.518, p = 0.000), especially related to memory. In terms of different types of cognitive training, specific CCT was more efficacious than non-specific CCT (g = 0.381, p = 0.007) or placebo (g = 0.734, p = 0.000) but not traditional CT (p = 0.628). In terms of stages of cognitive deterioration, the effect of CCT on SCD (g = 0.926, p = 0.002) was almost double that of its effect on MCI (g = 0.502, p = 0.000). CONCLUSION:CCT was most effective in cognitive rehabilitation, particularly in the subdomain of memory. Early intervention in SCD is better. 10.1007/s00415-019-09522-7
    Cognitive impairment three months after surgery is an independent predictor of survival time in glioblastoma patients. Butterbrod Elke,Synhaeve Nathalie,Rutten Geert-Jan,Schwabe Inga,Gehring Karin,Sitskoorn Margriet Journal of neuro-oncology PURPOSE:Cognitive functioning is increasingly investigated for its prognostic value in glioblastoma (GBM) patients, but the association of cognitive status during early adjuvant treatment with survival time is unclear. The aim of this study was to determine whether cognitive performance three months after surgical resection predicted survival time, while using a clinically intuitive time ratio (TR) statistic. METHODS:Newly diagnosed patients with GBM undergoing resection between November 2010 and February 2018 completed computerized cognitive assessment 3 months after surgery with the CNS Vital Signs battery (8 measures). The association of cognitive performance (continuous Z scores and dichotomous impairment status; impaired vs. unimpaired) with survival time was assessed with multivariate Accelerated Failure Time (AFT) models that also included clinical prognostic factors and covariates related to cognitive performances. RESULTS:114 patients were included in the analyses (median survival time 16.4 months). Of the clinical factors, postoperative Karnofsky Performance Status (TR 1.51), surgical (TR 2.20) and non-surgical (TR 1.94) salvage treatment, and pre-surgical tumor volume (cm, TR 1.003) were significant independent predictors of survival time. Independently of the base model factors and covariates, impairment on Stroop test I and Stroop test III estimated 23% and 26% reduction of survival time (TR 0.77, TR 0.74) respectively, as compared to unimpaired performance. CONCLUSION:These findings suggest that impaired performances on tests of executive control and processing speed in the early phase of adjuvant treatment can reflect a worse prognostic outlook rather than an early treatment effect, and their assessment might allow for early refinement of current prognostic stratification. 10.1007/s11060-020-03577-7
    Nicotinic treatment of post-chemotherapy subjective cognitive impairment: a pilot study. Vega Jennifer N,Albert Kimberly M,Mayer Ingrid A,Taylor Warren D,Newhouse Paul A Journal of cancer survivorship : research and practice PURPOSE:Persistent chemotherapy-related cognitive impairment (pCRCI) is commonly reported following cancer treatment and negatively affects quality of life; however, there is currently no pharmacological treatment indicated for pCRCI. This pilot study obtained preliminary data regarding the use of transdermal nicotine patches as a therapeutic strategy for women with pCRCI to (1) reduce subjective cognitive complaints and (2) enhance objective cognitive performance in breast, colon, lymphoma, or ovarian cancer survivors with pCRCI. METHODS:Participants were randomized to either placebo (n = 11) or transdermal nicotine (n = 11) for 6 weeks, followed by 2 weeks of treatment withdrawal for a total of 8 weeks. Participants were assessed using both subjective and objective measures of cognitive functioning at five visits before, during, and after treatment. RESULTS:Over the course of the study, women in both groups improved substantially in severity of self-reported cognitive complaints measured by Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairments regardless of treatment arm. Additionally, objective cognitive performance measures improved in both groups; however, there was no significant difference in improvement between groups. CONCLUSIONS:Due to a large placebo response, we were unable to determine if a drug effect was present. However, we did observe substantial improvement in self-reported cognitive symptoms, likely resulting from factors related to participation in the trial rather than specific drug treatment effects. TRIAL REGISTRATION:The study was registered with clinicaltrials.gov (trial registration: NCT02312943). IMPLICATIONS FOR CANCER SURVIVORS:These results suggest that women with pCRCI can exhibit improvement in subjective cognition, with attention paid to symptoms and close follow-up over a short period of time. 10.1007/s11764-019-00786-6
    Psychostimulants for cancer-related cognitive impairment in adult cancer survivors: a systematic review and meta-analysis. Miladi Nadia,Dossa Richi,Dogba Maman Joyce,Cléophat-Jolicoeur Marie Immacula Fabienne,Gagnon Bruno Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer BACKGROUND:Cognitive impairment is recognized as a common symptom experienced by cancer survivors which impacts on quality of life (QoL) and day-to-day activities. One of the treatment options is the use of psychostimulants but the evidence supporting its use remains unclear. OBJECTIVES:To identify the level of evidence of psychostimulants' effect on the management of cognitive impairment in adult cancer survivors. METHODS:Electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) and reference lists of relevant reviews were searched from inception to December 2017, with no language restrictions applied. Randomized controlled trials (RCTs), evaluating the effect of psychostimulants on cognitive impairment among cancer patients with no primary or secondary brain tumor or brain radiation, were included. The primary outcome was cognitive function changes, whereas secondary outcomes were adverse events (AEs) and QoL. RESULTS:Six RCTs were included: three studies investigating methylphenidate and three modafinil, with a total of 244 and 146 patients, respectively. Due to important differences in methodologies between studies, a meta-analysis was assumed inappropriate for the primary outcome. A narrative synthesis was performed. One study using methylphenidate and two using modafinil demonstrated improvements in some cognitive functions as measured by objective cognitive assessment tests. Psychostimulants did not improve QoL and were not associated with more AEs. CONCLUSION:To date, limited evidence is available to estimate the usefulness (or lack) of psychostimulants on cognitive function in this population. 10.1007/s00520-019-04907-w
    Neuropsychological functioning among patients with different types of cancer : Postchemotherapy cognitive impairment and implications for rehabilitation. Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater BACKGROUND:Chemotherapeutic drugs often contribute to the cognitive impairment observed in some individuals following chemotherapy treatment. Postchemotherapy cognitive impairment (PCCI) is referred to as a decline in a variety of neuropsychological measures after chemotherapy and has an acute onset. METHODS: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 6 months later (T3). RESULTS: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. CONCLUSIONS: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. 10.1007/s40211-020-00345-x
    A video-game based cognitive training for breast cancer survivors with cognitive impairment: A prospective randomized pilot trial. Bellens Anne,Roelant Ella,Sabbe Bernard,Peeters Marc,van Dam Peter A Breast (Edinburgh, Scotland) INTRODUCTION:We investigated whether a web-based cognitive training video game is an effective approach to improve cognitive decline in combination with our standard of care for rehabilitation of breast cancer (BC) patients. MATERIALS AND METHODS:Self-selected BC patients between 18 and 71 years old complaining of disturbing cognitive impairment were studied. The patients received access to a web-based internet video game and online cognitive assessments (Aquasnap, Cambridge, MyCQ™). The early intervention group (n = 23) had a training program of 6 months of at least three times a week for a minimum of 60 min of game playing per week at home in addition to standard of care rehabilitation. The delayed intervention (n = 23) received standard of care for three months, followed by three months of similar MyCQ training. Outcome measures were the MyCQ (sub)scores and Activity of Daily Life (ADL), mood, subjective cognition and functional cognitive status measured by classic neuropsychological tests. RESULTS:At baseline the means for CFQ (a measure of self-reported cognitive failure), anxiety, PSQI and self-reflectiveness were beyond normal range in both groups. CFQ improved significantly better in the intervention group (p = 0.029). Combining the evolution over time in the entire population a significant improvement was seen for overall MyCQ score, level of fear, physical and emotional role limitation, and health change (all p < 0.05), but self-reflectivess deteriorated (p < 0.05)). Significant differences in the various MyCQ subtests over time were: improved speed in choice reaction time, visual memory recognition, N back 1 and 2, coding, trail making test B, improved accuracy of N back 1 and 2 (all p < 0.05). CONCLUSION:A program of cognitive training improves cognitive functioning over time. "Aquasnap" has a beneficial effect on the perception of subjective cognitive functioning (CFQ) but the exact role of video gaming in this process remains uncertain. 10.1016/j.breast.2020.06.003
    Evaluation of a new online cognitive assessment tool in breast cancer survivors with cognitive impairment: a prospective cohort study. Bellens Anne,Roelant Ella,Sabbe Bernard,Peeters Marc,van Dam Peter A Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer INTRODUCTION:Currently cancer-related cognitive impairment (CRCI) is mainly assessed by means of questionnaires, which is very laborious for the patients and the supervising physician. We evaluated a new online cognitive assessment tool, the MyCognition Quotient (MyCQ, Cambridge) in breast cancer survivors with CRCI, and compared the results with a psychometric test measuring cognitive complaints, depression, and anxiety. MATERIALS AND METHODS:In this prospective study, 46 adult patients between 18 and 70 years old with a diagnosis of BC were studied, all complaining of disturbing cognitive impairment. They participated in a physical cognitive rehabilitation program. The patients had an online cognitive assessment (MyCQ Med by MyCognition) every 4 weeks on their home computer. In addition patients were assessed in the outpatient clinic by the principal investigator at baseline, after 3 and 6 months using the following validated neuro-psychological surveys: the Hospital Anxiety and Depression Scale (HADS), Beck Cognitive Insight Scale (BCIS), and Cognitive Failure Questionnaire (CFQ). MyCQ scores were correlated with the results of these surveys. RESULTS:Only weak correlations could be found between overall MyCQ or the MyCQ subtests with the psychometric tests (between - 0.43 and 0.458) at baseline and when combining data at time point 0, 3, and 6 months. Linear mixed models showed there was a significant association between Latency Choice Reaction Time and CFQ (continuous; p = 0.026). An AUC of 0.640 and a cut-off of 481.5 ms in Latency Choice Reaction Time were found to distinguish patients with CFQ below 44 to patients with CFQ above 44 (sensitivity 0.63 and specificity 0.73). In Latency Coding an AUC of 0.788 and a cut-off of 1316 ms were found to distinguish non-depressive patients from patients likely to present with depressive symptoms (sensitivity 0.75 and specificity 0.76). CONCLUSION:MyCQ cannot replace the various psychometric tests. However, abnormal Latency in cognitive tests, Choice Reaction Time and Coding, seems promising to be used as a screening tool to detect specific aspects of abnormal cognitive functioning in patients with cognitive complaints and depressive symptoms. 10.1007/s00520-021-06397-1
    Cancer-related cognitive impairment: a mixed methods evaluation of a standard factsheet. Lim Chloe Yi Shing,He Sharon,Shaw Joanne,Dhillon Haryana M Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:To understand the impact of cancer survivors accessing a standard factsheet regarding cancer-related cognitive impairment (CRCI), publicly available to the Australian public via Cancer Council Australia's websites. METHODS:Twenty-three cancer survivors completed a questionnaire assessing pre-factsheet knowledge of CRCI. Semi-structured interviews were conducted to explore participants' experiences of CRCI and perceptions of the factsheet. Interviews were analysed via thematic analysis using a framework approach. Finally, participants completed another questionnaire assessing post-factsheet change in knowledge of CRCI. RESULTS:Pre- and post-factsheet questionnaire change scores indicated increased knowledge and greater confidence about CRCI. Interview data resulted in five themes: generally positive perceptions of the factsheet's layout and wording; survivors, regardless of treatments received, experienced CRCI symptoms, with some having strong negative emotional responses to their symptoms; perceptions of the factsheet's strategies to manage CRCI ranged from relevant and useful, to impractical or unrealistic if symptoms were too severe; interactions with healthcare system influenced survivors' perceptions of help-seeking, with negative healthcare experiences a major barrier; and generally positive impacts of the factsheet, with survivors praising the factsheet's ability to validate the CRCI experience, increase CRCI knowledge, influence health beliefs, and prompt help-seeking. CONCLUSION:The factsheet presentation and wording were acceptable to participants. Its ability to normalise and raise awareness for CRCI validated participants' symptoms. The factsheet's potential as a first-line intervention in a stepped-care approach was identified, with participants finding the suggested self-management strategies practical. The factsheet may overcome barriers to self-reporting by encouraging patients to talk with HCPs about CRCI. 10.1007/s00520-021-06666-z
    Does my older cancer patient have cognitive impairment? Snaedal Jon Journal of geriatric oncology Cancer and impaired cognition are both frequent conditions in old age and consequently coexist to certain degree. The prevalence of impaired cognition increases sharply after the age of 65 and the more advanced form of cognitive impairment; dementia, is exceeding 30% by the age of 85years. Adequate cognition is crucial for understanding important facts and for giving consent for intervention. There are many different stages of cognitive impairment, ranging from subjective cognitive impairment to severe dementia. The mildest stages of cognitive impairment are sometimes reversible but in more severe stages, there is brain damage of some kind, most frequently caused by neurodegenerative disorder such as Alzheimer's disease. Therefore, some kind of evaluation of cognition should be offered to all older individuals with cancer and in need for intervention. In this evaluation, information should also be sought from a close relative. In the earlier stages of cognitive impairment, the individual usually retains ability to give consent and understands information given but in later stages of dementia, a surrogate decision maker is needed. In milder stages of dementia, an individual evaluation is needed for decision of capability for consent. A specific diagnosis of a disorder such as Alzheimer's disease does not in itself preclude the individual from giving consent, the degree of cognitive impairment, impaired judgement and poor insight are more decisive in this regard. It is also important to know the difference of delirium, most often a time limited condition and dementia that usually is progressive. 10.1016/j.jgo.2017.11.010
    Perceptions of a Health Care Notebook from Female Breast Cancer Survivors with Cognitive Impairment. Moyo Pamela,Walters Darrell,Siebens Hilary C,Myers Jamie,Baynes Rachel,Cook-Wiens Galen,Jo Mi-Yeoung,Asher Arash Journal of cancer education : the official journal of the American Association for Cancer Education Strengthening communication between providers and patients, especially those with cognitive impairment, is required given care complexity and fragmentation across the care continuum. Therefore, determining patient perceptions about the Siebens Health Care Notebook (SHCN), a tool to support self-management and strengthen communication and care continuity, is fundamental to understanding SHCN usability. Participants were breast cancer survivors in a study evaluating a 6-week cognitive rehabilitation program, who reported cancer-related cognitive impairment (Functional Assessment of Cancer Therapy-Cognitive Function-Perceived Cognitive Impairment (PCI) subscale < 59). Participant groups were alternately assigned to receive the SHCN (intervention) or not (control). SHCN recipients completed a 3-item qualitative perception survey at program completion. Both groups were surveyed at baseline, program completion, and 4 weeks later about communication with physicians. Scores were compared using Wilcoxon rank-sum tests. No baseline demographic or PCI score differences occurred between intervention (n = 29) and control (n = 16) groups. Of 22 (76%) who completed the SHCN perception survey, 100% endorsed it as useful in tracking health information, as helpful, and would recommend it to others. No group differences in communication activities with physicians were demonstrated. Women reporting cognitive impairment after breast cancer treatment perceived the SHCN as a beneficial self-care tool and would suggest it to others. Communication activities with physicians did not change during the study's short duration. Future research is needed to evaluate SHCN features contributing to helpfulness and details on use, including two-way communication activities between patients and physicians, across the care continuum. 10.1007/s13187-020-01753-x
    Early detection of cognitive impairment in patients with insulinoma. Dai Hongmei,Chen Hao,Hong Xiafei,Han Xianlin,Xu Qiang,Pang Haiyu,Yuan Jing,Wang Xianze,Xu Peiran,Jiang Jialin,Jiang Rui,Zhuang Zhe,Zhao Yupei,Wu Wenming Endocrine PURPOSE:Long-standing hypoglycemia can cause cognitive impairment, and whether recurrent severe hypoglycemia impacts cognitive function in patients with insulinoma has not been studied. This study focused on exploring the cognitive function in patients with insulinoma. METHODS:A prospective study was conducted to assess cognitive function in patients with insulinoma by administering the Montreal Cognitive Assessment (MoCA) questionnaire between January 2016 and July 2017, and patients with cognitive impairment were followed up to undergo the MoCA test 1 year after surgery. The MoCA scores after surgery were compared with the scores before surgery, and the associations between cognitive impairment and relevant factors were further evaluated by multiple linear regression analysis. RESULTS:Eighteen out of thirty-four patients (53%) with insulinoma were screened positive for cognitive impairment as defined by a MoCA score <26. Performance in certain cognitive domains, including visuospatial and executive functions, delayed memory, attention, language, and abstraction, was significantly worse in patients with cognitive impairment. Multivariate analysis indicated that MoCA scores correlated significantly with tumor grade and years of education. Eight patients with cognitive impairment were lost to follow-up. The remaining ten patients with cognitive impairment showed improvements 1 year postoperatively, and seven patients recovered to normal cognitive function. CONCLUSIONS:Cognitive impairment was found in patients with insulinoma and was reversible in some patients 1 year after surgery. More studies are needed to explore the underlying mechanisms of the existence and reversibility of cognitive impairment in patients with insulinoma. 10.1007/s12020-019-01994-x
    Effects of brief acceptance and commitment therapy (ACT) on subjective cognitive impairment in breast cancer patients undergoing chemotherapy. Shari Nurul Izzah,Zainal Nor Zuraida,Ng Chong Guan Journal of psychosocial oncology PURPOSE:This study examined the efficacy of a brief acceptance and commitment therapy (ACT) on subjective cognitive impairment in breast cancer patients undergoing chemotherapy. METHODS:Data collection was carried out in 3-time points: baseline (T1), screening (T2), and post-treatment (T3). Respondents who had significant subjective cognitive impairment were randomly divided into two groups: intervention (n = 30) and waitlist (n = 30). Respondents in the intervention group received 4 sessions of 1 hour of ACT therapy. FINDINGS:Respondents in the intervention group showed significant improvement in subjective cognitive impairment, depression, anxiety, and psychological inflexibility after the ACT intervention ( < 0.05). After controlling the covariates, group differences in all variables were significant except for fatigue and psychological inflexibility has the highest effect size ( = 4.69). CONCLUSION:ACT could be considered as an effective intervention to ameliorate subjective cognitive impairment, anxiety, depression, and psychological inflexibility in breast cancer patients undergoing chemotherapy. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS:This study highlights the importance of screening for subjective cognitive impairment in breast cancer patients undergoing chemotherapy and heightens their opportunity to receive proper management as earlier as possible. 10.1080/07347332.2020.1856283
    Cross sectional association between cytomegalovirus seropositivity, inflammation and cognitive impairment in elderly cancer survivors. Vivek Sithara,Nelson Heather Hammond,Prizment Anna E,Faul Jessica,Crimmins Eileen M,Thyagarajan Bharat Cancer causes & control : CCC PURPOSE:The higher prevalence of cognitive impairment/ dementia among cancer survivors is likely multifactorial. Since both exposures to cytomegalovirus (CMV) and inflammation are common among elderly cancer survivors, we evaluated their contribution towards dementia. METHODS:Data from 1387 cancer survivors and 7004 participants without cancer in the 2016 wave of the Health and Retirement Study (HRS) was used in this study. Two inflammatory biomarkers, C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR), were used to create an inflammation score. We used survey logistic regression adjusted for survey design parameters. RESULTS:CMV seropositivity was not associated with cognitive impairment among cancer survivors (p = 0.2). In addition, inflammation was associated with elevated odds of cognitive impairment (OR = 2.2, 95% CI [1.2, 4.2]). Cancer survivors who were both CMV seropositive and had increased inflammation had the highest odds of cognitive impairment compared to those who were CMV seronegative and had low inflammation (OR = 3.8, 95% CI [1.5, 9.4]). The stratified analysis among cancer survivors showed this association was seen only among cancer survivors in whom the cancer was diagnosed within three years of measurement of inflammation score and CMV serostatus (OR = 18.5; 95% CI [6.1, 56.1]). CONCLUSION:The CMV seropositivity and high inflammation was associated with higher cognitive impairment among cancer survivors. The stronger associations seen among cancer survivors diagnosed within the last three years suggest that strategies to reduce CMV activation and inflammation during or immediately after cancer treatment may be important in reducing the prevalence of cognitive impairment/ dementia among cancer survivors. 10.1007/s10552-021-01504-3
    Mice with pre-existing tumors are vulnerable to postoperative cognitive dysfunction. Wu Tong,Wang Xiaoqiang,Zhang Ruirui,Jiao Yingfu,Yu Weifeng,Su Diansan,Zhao Yanhua,Tian Jie Brain research Postoperative cognitive dysfunction (POCD) is a common long-term complication of surgery, which may have serious consequences for quality of life and may even result in irreversible cognitive deficits. With the aging of society, more patients are having surgery due to cancer. However, few studies have focused on postoperative cognitive function in cancer patients. Here, MC38 colon cancer cells (2 × 10/mouse) were injected subcutaneously into 2-month-old C57BL/6J mice 3 weeks before surgery to repair tibial fractures in order to establish a model of a tumor-bearing animal undergoing surgery. Both Morris water maze (MWM) and novel object recognition (NOR) tests indicated that cognitive impairment developed after surgery in tumor-bearing mice, whereas a single surgery or tumor alone had no effects on cognitive function in adult mice. The hippocampal expression of postsynaptic density protein 95 (PSD-95) 7 days post-operatively was consistent with the changes seen in the behavioral experiments. At 48 h post-surgery, significantly elevated levels of plasma TNF-α, IL-6 and IL-1β were detected in the tumor-bearing mice, but not in normal mice that had undergone surgery. Further analysis of the hippocampi also showed increased expression of TNF-α, IL-6 and IL-1β in tumor-bearing mice but not normal mice at the same time point, and the mRNA levels of these cytokines were consistent among the different groups. Furthermore, hippocampal microglia activation was absent and the permeability of the BBB was increased in tumor-bearing mice. These results indicate that mice with tumors develop POCD more easily. Prolonged central inflammation, which is mostly likely derived from heightened peripheral innate immunity, possibly underlies the cognitive impairment in tumor-bearing mice after surgery. 10.1016/j.brainres.2020.146650
    Neurobiological Mechanisms of Chemotherapy-induced Cognitive Impairment in a Transgenic Model of Breast Cancer. Winocur Gordon,Berman Hal,Nguyen Mary,Binns Malcolm A,Henkelman Mark,van Eede Matthijs,Piquette-Miller Micheline,Sekeres Melanie J,Wojtowicz J Martin,Yu Johnson,Zhang Haibo,Tannock Ian F Neuroscience Animal studies have reinforced clinical reports of cognitive impairment in cancer survivors following chemotherapy but, until now, all pre-clinical research in this area has been conducted on normal rodents. The present study investigated the effects of chemotherapy on cognition and underlying biological mechanisms in the FVB/N-Tg (MMTV-neu) 202 Mul/J mouse, a well-characterized transgenic model of breast cancer that has similarities to the tumorigenesis which occurs in humans. Tumor-bearing and control mice received three weekly injections of a combination of methotrexate + 5-fluorouracil, or an equal volume of saline. Different aspects of learning and memory were measured before and after treatment. The effects of tumor and chemotherapy on neurogenesis, neuro-inflammatory cytokine activity, and brain volume, as they relate to corresponding cognitive changes, were also measured. The toxic effects of chemotherapy extended to the cancerous model in which substantial cognitive impairment was also associated with the disease. Cognitive deficits were greatest in tumorigenic mice that received the anti-cancer drugs. Both tumor growth and chemotherapy caused significant changes in brain volume, including the hippocampus and frontal lobes, two structures that are directly implicated in cognitive tasks that were shown to be vulnerable. The level of hippocampal neurogenesis in adulthood was suppressed in chemotherapy-treated mice and associated with loss of hippocampus-controlled cognitive function. Dysregulation of cytokine activity was found in tumorigenic mice and associated with impaired cognitive performance. The results show that chemotherapy and tumor development independently contribute to cognitive deficits through different biological mechanisms. 10.1016/j.neuroscience.2017.10.048
    Oxidative stress and inflammatory markers in type 2 diabetic patients. Malik Aastha,Morya Rajesh Kumar,Saha Sarama,Singh Praveen Kumar,Bhadada Sanjay Kumar,Rana Satya Vati European journal of clinical investigation BACKGROUND:Type 2 diabetes mellitus (T2DM) is most demanding public health problem of 21st century. Uncontrolled diabetes may cause complications affecting any part of gut from mouth to rectum presenting as vomiting, nausea, bloating, abdominal pain, constipation and diarrhoea. The aim of this study was to compare levels of oxidative stress and inflammatory markers in small intestinal bacterial overgrowth (SIBO)-positive and negative diabetic patients. SUBJECTS AND METHODS:An observational analytical study was conducted on 300 T2DM (>5 years' duration) attending Diabetic Clinic. A total of 200 age- and sex-matched healthy individuals were enrolled as controls. Noninvasive glucose hydrogen breath test was used to diagnose SIBO. A total of 5 mL blood was taken. Plasma was used for measurement of inflammatory cytokines (TNF-α, IL-6 and IL-10) by ELISA. Hemolysate was used for measurement of lipid peroxidation, reduced GSH, superoxide dismutase and catalase. RESULTS:It was observed that constipation was present in 59.6% T2DM patients. SIBO was observed significantly higher (P < .0001) in T2DM patients than controls. Inflammatory and oxidative stress markers were significantly (P < .001) higher in diabetic and SIBO-positive patients than controls and SIBO negative. Reduced GSH was significantly (P < .05) lower whereas superoxide dismutase (SOD) and catalase antioxidant enzymes were significantly (<.05) higher in diabetic and SIBO-positive patients than controls and SIBO-negative patients. CONCLUSION:From this study, it could be concluded that SIBO in T2DM patients can cause oxidative stress and inflammation. Therefore, SIBO should be taken care to prevent further damage to intestine. 10.1111/eci.13238
    Increased serum interleukin-6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients. Tsai C-F,Chu C-J,Wang Y-P,Liu P-Y,Huang Y-H,Lin H-C,Lee F-Y,Lu C-L Alimentary pharmacology & therapeutics BACKGROUND:Sleep-wake disturbances are common in patients with cirrhosis and have a considerable effect on health-related quality of life; however, the underlying mechanism behind the phenomenon is unclear. Cytokines are involved in the mediation of signalling pathways regulating fibrogenesis, leading to cirrhosis. In addition, increased cytokines could contribute to sleep disturbances. AIM:To determine the relationship between pro-inflammatory cytokines and sleep disturbance in cirrhotic patients. METHODS:Ninety-eight nonalcoholic cirrhotic patients without overt hepatic encephalopathy were enrolled in this cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Psychometric Hepatic Encephalopathy Score (PHES) was used to examine cognitive performance and define minimal hepatic encephalopathy (MHE). The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the mood status of the patients. Pro-inflammatory cytokines that include interleukin 6 (IL-6) and tumour necrosis factor-α, as well as HBV-DNA or HCV-RNA levels were determined in patients. RESULTS:A total of 56 (57%) cirrhotic patients were identified as 'poor' sleepers (PSQI > 5). After multivariate analysis, IL-6 (P = 0.001) and HADS scores (P = 0.002) were found to be independent predictive factors of poor sleep quality. No significant relationships were observed between the sleep indices and the presence of MHE. HCV-RNA, but not HBV-DNA, viraemia was associated with sleep disturbance in cirrhotic patients. CONCLUSIONS:Sleep disturbance is found commonly in cirrhotic patients and a high serum IL-6 level is predictive of poor sleep quality. Minimal hepatic encephalopathy by itself may not contribute to sleep dysfunction in cirrhotic patients. 10.1111/apt.13765
    Cognitive decline after major oncological surgery in the elderly. Plas M,Rotteveel E,Izaks G J,Spikman J M,van der Wal-Huisman H,van Etten B,Absalom A R,Mourits M J E,de Bock G H,van Leeuwen B L European journal of cancer (Oxford, England : 1990) BACKGROUND:Elderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients. METHODS:A consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests. RESULTS:Of the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47-60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6-16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3-27). In patients with lower pre-operative Mini-Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18-57), and in patients undergoing major surgery it was 18% (95% CI: 10.6-26). Of the cognitive domains, executive function was the most vulnerable to decline. CONCLUSION:About half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation. 10.1016/j.ejca.2017.09.024
    Accelerated vascular aging and persistent cognitive impairment in older female breast cancer survivors. Carlson Barbara W,Craft Melissa A,Carlson John R,Razaq Wajeeha,Deardeuff Kelley K,Benbrook Doris M GeroScience Advances in breast cancer treatment have markedly increased survivorship over the past three decades, with over 3.1 million survivors expected to live into their 70s and 80s. Without symptom relief interventions, nearly 35% of these survivors will have life-altering and distressing cognitive symptoms. This pilot study explored associations between serum markers of vascular aging, laterality in cerebral oxygenation, and severity of cognitive impairment in women, 12-18 months after chemotherapy for stage 2/3 invasive ductal breast cancer. Fifteen women (52-84 years) underwent a brief cognitive assessment (Montreal Cognitive Assessment [MOCA]) and blood draws to assess markers of vascular aging (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], and insulin growth factor-1 [IGF-1]). All underwent a computer-based test protocol that is known to increase blood flow within the frontal lobes. Percent cerebral oxyhemoglobin saturation (rcSO) was recorded during and after testing. Laterality in rcSO was defined by ≥ 3% difference between left and right rcSO (|rcSO mean mean|). Eight participants had MOCA scores between 21 and 25 points, suggestive of mild cognitive impairment. Neither CRP (r = -.24) nor IL-6 (r = .34) nor TNF-α (r = .002) were associated with MOCA scores. Higher IL-6 was associated with greater laterality (r = .41). MOCA scores were significantly lower in subjects with laterality in rcSO than in those without laterality (F = 13.5, p = 003). Lower IGF-1 was significantly associated with greater laterality (r = - .66, p = .007) and lower cognitive function (r = .58). These findings suggest that persistent cognitive impairment is associated with phenotypical changes consistent with accelerated vascular aging. 10.1007/s11357-018-0025-z
    Replacing sedentary time with physical activity or sleep: effects on cancer-related cognitive impairment in breast cancer survivors. Ehlers Diane K,Fanning Jason,Salerno Elizabeth A,Aguiñaga Susan,Cosman Josh,Severson Joan,Kramer Arthur F,McAuley Edward BMC cancer BACKGROUND:Evidence suggests reallocating daily sedentary time to physical activity or sleep confers important health benefits in cancer survivors. Despite emerging research suggesting physical activity as a treatment for cancer-related cognitive impairment (CRCI), little is known about the interactive effects of behaviors across the 24-h period. The present purpose was to examine the cognitive effects of reallocating sedentary time to light-intensity physical activity, moderate-to-vigorous physical activity (MVPA), or sleep in breast cancer survivors. METHODS:Breast cancer survivors (N = 271, Mage = 57.81 ± 9.50 years) completed iPad-based questionnaires and cognitive tasks assessing demographics, health history, executive function, and processing speed (Task-Switch, Trail Making). Participants wore an accelerometer for seven consecutive days to measure their sedentary, physical activity, and sleep behaviors. Single effects (each behavior individually) and partition (controlling for other behaviors) models were used to examine associations among behaviors and cognitive performance. Isotemporal substitution models were used to test the cognitive effects of substituting 30 min of sedentary time with 30 min of light-intensity activity, MVPA, and sleep. RESULTS:MVPA was associated with faster Task-switch reaction time in the partition models (stay: B = - 35.31, p = 0.02; switch: B = - 48.24, p = 0.004). Replacing 30 min of sedentary time with 30 min of MVPA yielded faster reaction times on Task-Switch stay (B = - 29.37, p = 0.04) and switch (B = - 39.49, p = 0.02) trials. In Trails A single effects models, sedentary behavior was associated with faster completion (B = - 0.97, p = 0.03) and light-intensity activity with slower completion (B = 1.25, p = 0.006). No single effects were observed relative to Trails B completion (all p > 0.05). Only the effect of MVPA was significant in the partition models (Trails A: B = - 3.55, p = 0.03; Trails B: B = - 4.46, p = 0.049). Replacing sedentary time with light-intensity activity was associated with slower Trails A (B = 1.55 p = 0.002) and Trails B (B = 1.69, p = 0.02) completion. Replacing light activity with MVPA yielded faster Trails A (B = - 4.35, p = 0.02) and Trails B (B = - 5.23, p = 0.03) completion. CONCLUSIONS:Findings support previous research suggesting MVPA may be needed to improve cognitive function in breast cancer survivors. Trails findings underscore the need to dissect sedentary contexts to better understand the impact of daily behavioral patterns on CRCI. Additional research investigating the cognitive impacts of behaviors across the 24-h period is warranted. TRIAL REGISTRATION:This study is registered with United States ClinicalTrials.gov ( NCT02523677 ; 8/14/2015). 10.1186/s12885-018-4603-3
    Multi-angles of smoking and mild cognitive impairment: is the association mediated by sleep duration? Hu Mingyue,Yin Huiru,Shu Xinhui,Jia Yong,Leng Minmin,Chen Li Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology Although the association between cigarette smoking and risk of mild cognitive impairment (MCI) is controversial, most recent studies have shown that this influence is negative. However, it is unknown how multiple factors of smoking affect MCI, and the mechanisms of different smoking factors are not yet clarified. This study will examine the impact of various angles of smoking on MCI and the potential mediating effects of sleep duration on smoking MCI association in the elderly. In the case group, 109 elderly people who met the inclusion criteria were selected, and 123 were selected in the control group. Participant characteristics include sleep duration and a detailed lifetime history of smoking. After adjusting the relevant covariates, higher odds of MCI occurrence were found in ex-smokers/current smokers; moderate/heavy smokers; smokers for 30-44, 45-59 and more than 60 years; smokers with cumulative smoking duration of 30-44 or more than 60 years and smokers with cumulative dose smoking intensity of 200-399 or 400-599 cigarettes monthly. Elderly subjects who had quit smoking for 21 years or longer were found to have lower odds of MCI occurrence. The indirect effects of smoking on MCI via sleep duration were statistically significant, as the ratio of indirect effect to total effect ranged from 0.14 to 0.29. Smoking affects cognitive function through multi-angles of smoking and influences the cognitive function partly via the duration of sleep. 10.1007/s10072-019-03750-5
    Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. Shen Xue-Ning,Niu Li-Dong,Wang Yan-Jiang,Cao Xi-Peng,Liu Qiang,Tan Lan,Zhang Can,Yu Jin-Tai Journal of neurology, neurosurgery, and psychiatry OBJECTIVE:Inflammation plays a crucial role in the pathogenesis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Our study aimed to analyse previous inconsistent results of inflammatory markers in AD and MCI quantitatively. METHODS:Studies reporting concentrations of peripheral or cerebrospinal fluid (CSF) markers were included, and eligible data on AD, MCI and control were extracted. Pooled Hedges's g was adopted to illustrate comparisons, and various confounding factors were used to explore sources of heterogeneity. RESULTS:A total of 170 studies were included in the meta-analysis and systematic review, which demonstrated increased peripheral levels of high-sensitivity C reactive protein (Hedges's g 0.281, p<0.05), interleukin-6 (IL-6) (0.429, p<0.005), soluble tumour necrosis factor receptor 1 (sTNFR1) (0.763, p<0.05), soluble tumour necrosis factor receptor 2 (sTNFR2) (0.354, p<0.005), alpha1-antichymotrypsin (α1-ACT) (1.217, p<0.005), IL-1β (0.615, p<0.05) and soluble CD40 ligand (0.868, p<0.005), and CSF levels of IL-10 (0.434, p<0.05), monocyte chemoattractant protein-1 (MCP-1) (0.798, p<0.005), transforming growth factor-beta 1 (1.009, p<0.05), soluble triggering receptor expressed on myeloid cells2 (sTREM2) (0.587, p<0.001), YKL-40 (0.849, p<0.001), α1-ACT (0.638, p<0.001), nerve growth factor (5.475, p<0.005) and visinin-like protein-1 (VILIP-1) (0.677, p<0.005), in AD compared with the control. Higher levels of sTNFR2 (0.265, p<0.05), IL-6 (0.129, p<0.05) and MCP-1 (0.779, p<0.05) and lower levels of IL-8 (-1.293, p<0.05) in the periphery, as well as elevated concentrations of YKL-40 (0.373, p<0.05), VILIP-1 (0.534, p<0.005) and sTREM2 (0.695, p<0.05) in CSF, were shown in MCI compared with the control. Additionally, increased peripheral sTNFR1 (0.582, p<0.05) and sTNFR2 (0.254, p<0.05) levels were observed in AD compared with MCI. CONCLUSION:Significantly altered levels of inflammatory markers were verified in comparison between AD, MCI and control, supporting the notion that AD and MCI are accompanied by inflammatory responses in both the periphery and CSF. 10.1136/jnnp-2018-319148
    Association between patient-reported hearing and visual impairments and functional, psychological, and cognitive status among older adults with cancer. Soto-Perez-de-Celis Enrique,Sun Can-Lan,Tew William P,Mohile Supriya Gupta,Gajra Ajeet,Klepin Heidi D,Owusu Cynthia,Gross Cary Philip,Muss Hyman B,Lichtman Stuart M,Chapman Andrew E,Cohen Harvey Jay,Dale William,Kim Heeyoung,Fernandes Simone,Katheria Vani,Hurria Arti Cancer BACKGROUND:Hearing and visual impairments are common among community-dwelling older adults, and are associated with psychological, functional, and cognitive deficits. However, to the authors' knowledge, little is known regarding their prevalence among older patients with cancer. METHODS:The current study was a secondary analysis combining 2 prospective cohorts of adults aged ≥65 years with solid tumors who were receiving chemotherapy. The authors assessed the association between patient-reported hearing and/or visual impairment (defined as fair/poor grading by self-report) and physical function, instrumental activities of daily living (IADLs), anxiety, depression, and cognition. Descriptive analyses were conducted to summarize patient and treatment characteristics. One-way analysis of variance and chi-square tests were conducted as appropriate to examine differences between patients with and without sensory impairments. Logistic regression was used to analyze associations between sensory impairments and outcomes. RESULTS:Among 750 patients with a median age of 72 years who had solid tumors (29% with breast/gynecological tumors, 28% with lung tumors, and 27% with gastrointestinal tumors), approximately 18% reported hearing impairment alone, 11% reported visual impairment alone, and 7% reported dual sensory impairment. Hearing impairment was associated with IADL dependence (odds ratio [OR], 1.9), depression (OR, 1.6), and anxiety (OR, 1.6). Visual impairment was associated with IADL dependence (OR, 1.9), poor physical function (OR, 1.9), and depression (OR, 2.5). Dual impairment was associated with IADL dependence (OR, 2.8), anxiety (OR, 2.3), depression (OR, 2.5), and cognitive impairment (OR, 3.2). CONCLUSIONS:Sensory impairment is common among older adults with cancer. Patients with sensory impairment are more likely to have functional, psychological, and cognitive deficits. Interventions aimed at improving the vision and hearing of older adults with cancer should be studied. Cancer 2018. © 2018 American Cancer Society. 10.1002/cncr.31540
    Treating cancer therapy-related cognitive impairment. Gibson Erin M,Monje Michelle Nature medicine 10.1038/s41591-020-1014-1
    Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction. Wardill Hannah R,Mander Kimberley A,Van Sebille Ysabella Z A,Gibson Rachel J,Logan Richard M,Bowen Joanne M,Sonis Stephen T International journal of cancer Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. 10.1002/ijc.30252
    Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy. Dhillon Haryana M,Tannock Ian F,Pond Gregory R,Renton Corrinne,Rourke Sean B,Vardy Janette L Journal of cancer survivorship : research and practice PURPOSE:Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains. METHODS:Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL). RESULTS:Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28-0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44-0.51) in CRC patients. CONCLUSIONS:No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory. TRIAL REGISTRATION:The study was registered with clinicaltrials.gov (trial registration: NCT00188331). IMPLICATIONS FOR CANCER SURVIVORS:Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls. 10.1007/s11764-017-0656-6
    Inflammation and behavioral symptoms in preoperational glioma patients: Is depression, anxiety, and cognitive impairment related to markers of systemic inflammation? Song Li,Quan Xingyun,Su Lin,Wang Ke,Wang Haorun,Wu Lihong,Chen Chaoyi,Li Shenjie,Xiang Wei,Chen Ligang,Zhou Jie Brain and behavior PURPOSE:Behavioral symptoms, including depression, anxiety, and cognitive impairment, are common clinical symptoms of patients with glioma. However, the mechanisms underlying the behavioral symptoms of glioma patients remain unclear. In this study, we explore the correlation between markers of systemic inflammation and preoperational behavioral symptoms in glioma patients. PATIENTS AND METHODS:Patients (n = 71) who had recently undertaken imaging (i.e., CT, MRI) for suspected glioma had a face-to-face interview, completed self-report scales, and provided blood samples. Furthermore, we tested blood samples by a protein chip to select differential inflammatory cytokines and further confirm such differences using liquid-phase chip technology. RESULTS:The prevalence of depression, anxiety, and cognitive impairment in glioma patients prior to surgery in this study was 53.5%, 70.4%, and 32.4%, respectively. The increased levels of IFN-γ were positively correlated with clinical symptoms of depression in the glioma patients. Moreover, increased IL-2 levels were negatively associated with anxiety symptoms (p = .00) and positively correlated with cognitive impairment in glioma patients. CONCLUSION:This study suggests that systemic inflammation is associated with behavioral symptoms in glioma patients. This provides further evidence of the contribution of inflammatory markers to psychological symptoms in the context of physical conditions and lays the foundation for the development of further treatments of the behavioral symptoms in glioma patients. 10.1002/brb3.1771
    Cognitive Impairment in a Subset of Breast Cancer Patients After Systemic Therapy-Results From a Longitudinal Study. Menning Sanne,de Ruiter Michiel B,Kieffer Jacobien M,Agelink van Rentergem Joost,Veltman Dick J,Fruijtier Agnetha,Oldenburg Hester S A,Boven Epie,van der Meij Suzan,Lustig Vera,Bos Monique E M,Boogerd Willem,Reneman Liesbeth,Schagen Sanne B Journal of pain and symptom management CONTEXT:Studies indicate adverse effects of breast cancer (BC) and cancer treatment on cognitive function. OBJECTIVES:To investigate the effects of systemic treatment on cognitive performance in BC patients. METHODS:Participants were BC patients scheduled to receive systemic treatment (BC + SYST; n = 31), or no systemic treatment (BC; n = 24) and no-cancer (NC) controls (n = 33). Neuropsychological examinations were used to study cognitive performance on 18 tests grouped into eight cognitive domains, before adjuvant treatment (T1) and six months after chemotherapy (T2), or at similar intervals. We also assessed health-related quality of life, anxiety and depression, mood, stress, and cognitive problems. Analysis of variance was used to assess group differences of cognitive performance and multivariate normative comparison to classify impairment, comparing scores of each participant against the distribution of the scores of NC controls. RESULTS:Of BC + SYST, 16% were cognitively impaired at T2, compared to 4% in BC and 6% in NC. Although not significant, we observed moderate effect sizes for worse performance in the BC + SYST group compared to NC (Flanker congruent [effect size {ES} = 0.44] and stimulus incongruent [ES = 0.44]) and compared to BC (Controlled Oral Word Association Test [ES = 0.47], digit span [ES = 0.41], and Hopkins Verbal Learning Test immediate [ES = 0.71] and delayed recall [ES = 0.65]). Cognitively impaired patients had a significantly lower estimated premorbid intelligence, worse physical and social functioning, and more distress at T2 compared to unimpaired patients. CONCLUSION:Our findings indicate that cognitive impairment after systemic treatment occurs in a subset of BC patients. The predictive value of demographic and psychosocial factors in cognitive impairment should be further investigated in a larger sample of impaired patients. 10.1016/j.jpainsymman.2016.04.012
    TNF-α and its soluble receptors mediate the relationship between prior severe mood episodes and cognitive dysfunction in euthymic bipolar disorder. Millett C E,Harder J,Locascio J J,Shanahan M,Santone G,Fichorova R N,Corrigan A,Baecher-Allan C,Burdick K E Brain, behavior, and immunity BACKGROUND:Bipolar disorder (BD) is one of the most disabling mental health conditions in the world. Symptoms of cognitive impairment in BD contribute directly to occupational and social deficiencies and are very difficult to treat. Converging evidence suggests that BD patients have increased peripheral markers of inflammation. The hypothesis of neuroprogression in BD postulates that cognitive deficits develop over the course of the illness and are influenced by prior severe mood episodes, leading to wear-and-tear on the brain- however, there exists a paucity of data statistically testing a mediating role of immune molecules in cognitive dysfunction in BD. METHODS:This is a cross-sectional study. We measured serum levels of tumor necrosis factor alpha (TNF-α), and soluble (s) TNF receptors one and two (sTNF-R1 and sTNF-R2) in 219 euthymic BD patients and 52 Healthy Controls (HCs). Structural equation modeling (SEM) was used for the primary purpose of assessing whether TNF markers (measured by the multiple indicators TNF-α, sTNF-R1 and sTNF-R2) mediate the effect or number of prior severe mood episodes (number of prior psychiatric hospitalizations) on cognitive performance. RESULTS:BD and HC groups did not differ on circulating levels of TNF molecules in the present study. However, we found higher sTNF-R1 concentration in 'late-stage' BD illness (>1 prior psychiatric hospitalization) compared to those in early stage illness. In the subsequent SEM, we found that the model fits the data acceptably (Chi-square = 49.2, p = 0.3), and had a 'close fit' (RMSEA = 0.02, PCLOSE = 0.9). Holding covariates constant (age, sex, premorbid IQ, education, and race), we found that the standardized indirect effect was significant, p = 0.015, 90%CI [-0.07, -0.01], indicating that the estimated model was consistent with peripheral TNF markers partially mediating a causal effect of severe mood episodes on executive function. CONCLUSIONS:Our results indicate that circulating levels of TNF molecules partially mediate the relationship between prior severe mood episodes and executive function in BD. These results may implicate TNF variables in the neuroprogressive course of BD and could point to novel interventions for cognition. 10.1016/j.bbi.2020.04.003
    Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping. Saria Marlon Garzo,Courchesne Natasia,Evangelista Lorraine,Carter Joshua,MacManus Daniel A,Gorman Mary Kay,Nyamathi Adeline M,Phillips Linda R,Piccioni David,Kesari Santosh,Maliski Sally Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. METHODS:We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). RESULTS:Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. CONCLUSIONS:Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases. 10.1007/s00520-016-3517-3
    Subjective cognitive functioning and associations with psychological distress in adult brain tumour survivors. Nicol Chelsea,Ownsworth Tamara,Cubis Lee,Nguyen William,Foote Matthew,Pinkham Mark B Journal of cancer survivorship : research and practice PURPOSE:The impact of brain tumour on subjective cognitive function (SCF) has received little attention despite the implications of these perceptions for quality of life. SCF consists of two related yet distinct components, perceived cognitive impairment (PCI) and perceived cognitive abilities (PCA). This study compared the SCF of adult brain tumour survivors and healthy controls and examined demographic, illness-related, and psychological factors associated with SCF. METHOD:Sixty-five adult survivors with primary brain tumour (age, 22-75 years), and 65 age- and sex-matched controls were recruited. Participants with brain tumour completed the Brief Test of Adult Cognition by Telephone, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), ratings of physical symptoms, Depression Scale of the Depression Anxiety Stress Scales-21 (DASS-Depression), and Generalized Anxiety Disorder-7 (GAD-7) scale. Controls completed the FACT-Cog, DASS-Depression, and GAD-7. RESULTS:Adult brain tumour survivors reported significantly greater PCI and lower PCA than controls, after accounting for anxiety. Higher PCI was significantly related to fatigue, pain, treatment-related side-effects, anxiety, and depression. Lower PCA was significantly associated with fatigue, pain, poorer objective cognitive function, lower education, anxiety, and depression. Anxiety uniquely accounted for 9-14% of variance in SCF. CONCLUSIONS:Adult brain tumour survivors were found to experience poorer SCF than healthy controls after accounting for anxiety. SCF was related to multiple factors after brain tumour; however, an independent association with anxiety was identified. IMPLICATIONS FOR CANCER SURVIVORS:These findings highlight the potential value of psychological interventions targeting anxiety and cognitive effects to improve quality of survivorship after brain tumour. 10.1007/s11764-019-00784-8
    Systematic review of longitudinal studies on chemotherapy-associated subjective cognitive impairment in cancer patients. Kim Hee-Ju,Jung Sun-Ok,Kim Hyang,Abraham Ivo Psycho-oncology OBJECTIVES:This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues. METHODS:Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors). RESULTS:Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed. CONCLUSION:More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI. 10.1002/pon.5339
    A Call for a Neuroscience Approach to Cancer-Related Cognitive Impairment. Horowitz Todd S,Suls Jerry,Treviño Melissa Trends in neurosciences Cancer-related cognitive impairment (CRCI) is a widespread problem for the increasing population of cancer survivors. Our understanding of the nature, causes, and prevalence of CRCI is hampered by a reliance on clinical neuropsychological methods originally designed to detect focal lesions. Future progress will require collaboration between neuroscience and clinical neuropsychology. 10.1016/j.tins.2018.05.001
    Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors. Ren Xiaojia,Boriero Diana,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Biochimica et biophysica acta. Molecular basis of disease Increasing numbers of cancer patients survive and live longer than five years after therapy, but very often side effects of cancer treatment arise at same time. One of the side effects, chemotherapy-induced cognitive impairment (CICI), also called "chemobrain" or "chemofog" by patients, brings enormous challenges to cancer survivors following successful chemotherapeutic treatment. Decreased abilities of learning, memory, attention, executive function and processing speed in cancer survivors with CICI, are some of the challenges that greatly impair survivors' quality of life. The molecular mechanisms of CICI involve very complicated processes, which have been the subject of investigation over the past decades. Many mechanistic candidates have been studied including disruption of the blood-brain barrier (BBB), DNA damage, telomere shortening, oxidative stress and associated inflammatory response, gene polymorphism of neural repair, altered neurotransmission, and hormone changes. Oxidative stress is considered as a vital mechanism, since over 50% of FDA-approved anti-cancer drugs can generate reactive oxygen species (ROS) or reactive nitrogen species (RNS), which lead to neuronal death. In this review paper, we discuss these important candidate mechanisms, in particular oxidative stress and the cytokine, TNF-alpha and their potential roles in CICI. 10.1016/j.bbadis.2019.02.007
    Chemotherapy-related cognitive impairment in older patients with cancer. Loh Kah Poh,Janelsins Michelle C,Mohile Supriya G,Holmes Holly M,Hsu Tina,Inouye Sharon K,Karuturi Meghan S,Kimmick Gretchen G,Lichtman Stuart M,Magnuson Allison,Whitehead Mary I,Wong Melisa L,Ahles Tim A Journal of geriatric oncology 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. 10.1016/j.jgo.2016.04.008
    Identification of the predictors of cognitive impairment in patients with cancer in palliative care: a prospective longitudinal analysis. Kurita Geana Paula,Benthien Kirstine Skov,Sjøgren Per,Kaasa Stein,Hjermstad Marianne Jensen Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Studies with neuropsychological assessments in patients with cancer are sparse, and the evidence is very limited regarding their status of cognitive function over time. This study aimed at assessing the prevalence and predictors of cognitive impairment in patients with cancer in palliative care. METHODS:Prospective longitudinal investigation derived from the European Palliative Care Cancer Symptom study (2011-2013) including patients with cancer in palliative care, ≥18 years, and with at least one assessment post-inclusion. For cognitive assessment, a 4-item version of the Mini Mental State Examination was applied at inclusion and after 4 to 16 weeks. Logistic regression model with multiple imputations was applied. RESULTS:The sample consisted of 1568 patients (50% male, mean age 65.5, 42% with 10-12 years schooling, mean Karnofsky Performance Status-KPS 68%). Longitudinal analysis of the patients with complete MMSE at both assessments (n = 801) showed that 64.5% were not impaired, 12.5% remained cognitively impaired, 11.4% developed impairment, and 11.6% improved. Those who improved cognitively also reported reduced pain intensity and increased appetite. The predictive model (n = 1351) showed that those with low KPS (OR = 1.6, 95% CI 1.0-2.5) most often developed cognitive impairment, while patients with breast cancer (OR = 0.4, 95% CI 0.2-0.7) had lower odds for impairment. CONCLUSIONS:During palliative care, a substantial number of patients remained cognitively impaired or developed cognitive impairment; however, it is noteworthy that improvement was also observed. Physical performance and cancer type may predict cognitive impairment. 10.1007/s00520-016-3485-7
    Association of Fatigue Intensification with Cognitive Impairment during Radiation Therapy for Prostate Cancer. Feng Li Rebekah,Espina Alexandra,Saligan Leorey N Oncology PURPOSE:Cancer-related fatigue is a common complaint during cancer treatment and is often associated with cognitive impairment. This study examined cognitive deficits that were associated with fatigue symptoms during external-beam radiation therapy (EBRT) in men with localized prostate cancer. METHODS:A total of 36 participants were enrolled and followed up at baseline, 24 h, 7 days, 14 days after EBRT initiation, at midpoint, and at completion of EBRT. Fatigue was measured by self-report using the Functional Assessment of Cancer Therapy - Fatigue (FACT-F), and cognitive impairment by the Computer Assessment of Mild Cognitive Impairment (CAMCI®). RESULTS:Subjects with increased fatigue during EBRT reported a significant decline in cognitive function and had difficulties with CAMCI®'s route finding and item recall tasks during EBRT. Increased fatigue during EBRT was associated with perceived cognitive difficulties in executive function and recognition memory, but not with attention or verbal memory. CONCLUSIONS:Our results suggest that there might be specific cognitive domains that are associated with increased fatigue during EBRT. These findings will provide important information for targeting specific cognitive domains using pharmacotherapy or behavioral interventions. CAMCI® is a valuable tool for psycho social providers to detect subtle cognitive impairment in fatigued cancer patients in a clinical setting. 10.1159/000487081
    Diet and cognitive function in cancer survivors with cancer-related cognitive impairment: A qualitative study. Coro Daniel G,Hutchinson Amanda D,Banks Siobhan,Coates Alison M European journal of cancer care OBJECTIVE:To identify cancer survivors' perceptions of the role diet plays in their cognitive function, and how their cancer-related cognitive changes influence their diet. METHODS:Cancer survivors diagnosed with cancer in the past 5 years, not on active treatment, and with self-reported cognitive changes since diagnosis were recruited from the general population. Semi-structured interviews were conducted with 15 Australian breast (n = 13) and colorectal (n = 2) survivors (mean time since diagnosed: 27.0 months ± SD=16.8). Questions related to how their diet and cognitive changes influenced each other. Interviews were recorded, and transcripts were analysed using thematic analysis. RESULTS:Four themes related to how diet impacted cognition: (a) directly (e.g. healthy diet improves cognition), (b) indirectly (e.g. diet affects tiredness which affects cognition); (c) no impact; and (d) potentially (e.g. poorer diet quality would worsen cognition). Three themes emerged for how cognitive changes were thought to impact survivors' diets: (a) planning meals is harder; (b) cooking is more difficult and complex; and, (c) choosing healthy is more challenging. CONCLUSIONS:Many cancer survivors perceived a bidirectional influence between diet and cognition that has cognitive and behavioural consequences. Diet could be investigated as a modifiable lifestyle behaviour to improve cancer-related cognitive impairment and fatigue. Survivors may benefit from dietary guidance with meal planning and preparing. 10.1111/ecc.13303
    Association of mitochondrial DNA content in peripheral blood with cancer-related fatigue and chemotherapy-related cognitive impairment in early-stage breast cancer patients: a prospective cohort study. Chae Jung-Woo,Chua Peh Siang,Ng Terence,Yeo Angie Hui Ling,Shwe Maung,Gan Yan Xiang,Dorajoo Sreemanee,Foo Koon Mian,Loh Kiley Wei-Jen,Koo Si-Lin,Chay Wen Yee,Tan Tira Jing Ying,Beh Sok Yuen,Lim Elaine Hsuen,Lee Guek Eng,Dent Rebecca,Yap Yoon Sim,Ng Raymond,Ho Han Kiat,Chan Alexandre Breast cancer research and treatment PURPOSE:Cancer-related fatigue (CRF) and chemotherapy-related cognitive impairment (CRCI) are reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF and CRCI. This study aims to evaluate the association between peripheral blood mtDNA content reduction and severity of CRF and CRCI in patients receiving chemotherapy. METHODS:This was a prospective cohort study. Early-stage breast cancer patients receiving anthracycline- or taxane-based chemotherapy were recruited. CRF was assessed using MFSI-SF, and CRCI was assessed using FACT-Cog and CANTAB at two timepoints: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). mtDNA content was measured at both timepoints using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF and CRCI, adjusting for age, anxiety, insomnia, plasma cytokines concentrations, and other clinically important covariates. RESULTS:A total of 108 patients (age 52.0 ± 9.2 years; 82.4% Chinese; 64.8% receiving anthracycline-based chemotherapy) were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (22.2, 33.3, 55.6, and 63.0% in quartiles 1, 2, 3, and 4, respectively, p = 0.001 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF and CRCI compared to those without CRF [mean reduction (± SD): 36.5 (46.1) vs. 9.4 (34.5), p < 0.001]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increased risk for worsening of CRF (95% CI, 1-6%; p = 0.009). CONCLUSIONS:This is the first study to show that the reduction of mtDNA content in peripheral blood is associated with the onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings. 10.1007/s10549-017-4640-7
    Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group. Mayo Samantha J,Lustberg Maryam,M Dhillon Haryana,Nakamura Zev M,Allen Deborah H,Von Ah Diane,C Janelsins Michelle,Chan Alexandre,Olson Karin,Tan Chia Jie,Toh Yi Long,Oh Jeong,Grech Lisa,Cheung Yin Ting,Subbiah Ishwaria Mohan,Petranovic Duska,D'Olimpio James,Gobbo Margherita,Koeppen Susanne,Loprinzi Charles L,Pang Linda,Shinde Shivani,Ntukidem Olanipekun,Peters Katherine B Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management. 10.1007/s00520-020-05860-9
    How to assess and manage cognitive impairment induced by treatments of non-central nervous system cancer. Lange Marie,Castel Hélène,Le Fel Johan,Tron Laure,Maillet Didier,Bernaudin Myriam,Touzani Omar,Perrier Joy,Boone Mathieu,Licaj Idlir,Giffard Bénédicte,Dubois Martine,Rigal Olivier,Durand Thomas,Belin Catherine,Ricard Damien,Le Gal Rozenn,Pancré Véronique,Hardy-Léger Isabelle,Joly Florence Neuroscience and biobehavioral reviews A number of neurotoxicity associated with oncological treatments has been reported in non-central nervous system cancers. An expert group presents the state of the art and a guide to help the choice of appropriated tools to assess patient cognition in studies on oncology and neurobehavior in animal models. In addition, current cognitive rehabilitation programs currently under evaluation are also discussed. Cognitive assessments in oncology depend on the research question, study design, cognitive domains, patients' characteristics, psychometric properties of the tests, and whether the tests are supervised or not by a neuropsychologist. Batteries of electronic tests can be proposed, but several of them are characterized by weak psychometric developments. In order to improve the comprehension on the impact of cancer treatments on cognition, new animal models are in development, and would in the future include non-human primate models. By bringing together the skills and practices of oncologists, neurologists, neuropsychologists, neuroscientists, we propose a series of specific tools and tests that accompany the cognitive management of non-CNS cancer patients. 10.1016/j.neubiorev.2019.09.028
    Sex-specific effects of high-fat diet on cognitive impairment in a mouse model of VCID. Salinero Abigail E,Robison Lisa S,Gannon Olivia J,Riccio David,Mansour Febronia,Abi-Ghanem Charly,Zuloaga Kristen L FASEB journal : official publication of the Federation of American Societies for Experimental Biology Mid-life metabolic disease (ie, obesity, diabetes, and prediabetes) causes vascular dysfunction and is a risk factor for vascular contributions to cognitive impairment and dementia (VCID), particularly in women. Using middle-aged mice, we modeled metabolic disease (obesity/prediabetes) via chronic high-fat (HF) diet and modeled VCID via unilateral common carotid artery occlusion. VCID impaired spatial memory in both sexes, but episodic-like memory in females only. HF diet caused greater weight gain and glucose intolerance in middle-aged females than males. HF diet alone impaired episodic-like memory in both sexes, but spatial memory in females only. Finally, the combination of HF diet and VCID elicited cognitive impairments in all tests, in both sexes. Sex-specific correlations were found between metabolic outcomes and memory. Notably, both visceral fat and the pro-inflammatory cytokine tumor necrosis factor alpha correlated with spatial memory deficits in middle-aged females, but not males. Overall, our data show that HF diet causes greater metabolic impairment and a wider array of cognitive deficits in middle-aged females than males. The combination of HF diet with VCID elicits deficits across multiple cognitive domains in both sexes. Our data are in line with clinical data, which shows that mid-life metabolic disease increases VCID risk, particularly in females. 10.1096/fj.202000085R
    Chemotherapy-induced cognitive impairment: focus on the intersection of oxidative stress and TNFα. Rummel Nicole G,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Cellular and molecular life sciences : CMLS Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of pathways as well as inhibit pathways necessary for proper brain function. Oxidative stress triggers the activation of different proteins, one in particular is tumor necrosis factor alpha (TNFα). Following treatment with various chemotherapy agents, this pro-inflammatory cytokine binds to its receptors at the blood-brain barrier and translocates to the parenchyma via receptor-mediated endocytosis. Once in brain, TNFα initiates pathways that may eventually lead to neuronal death and ultimately cognitive impairment. TNFα activation of the c-jun N-terminal kinases (JNK) and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways may contribute to both memory decline and loss of higher executive functions reported in patients after chemotherapy treatment. Chemotherapy also affects the brain's antioxidant capacity, allowing for accumulation of ROS. This review expands on these topics to provide insights into the possible mechanisms by which the intersection of oxidative stress and TNFΑ are involved in chemotherapy-induced cognitive impairment. 10.1007/s00018-021-03925-4
    Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors. Regier Natalie G,Naik Aanand D,Mulligan Elizabeth A,Nasreddine Ziad S,Driver Jane A,Sada Yvonne H-F,Moye Jennifer Psycho-oncology OBJECTIVE:This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS:A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS:Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS:CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency. 10.1002/pon.5131
    Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study. Zeng Yingchun,Cheng Andy S K,Song Ting,Sheng Xiujie,Zhang Yang,Liu Xiangyu,Chan Chetwyn C H BMC cancer BACKGROUND:Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. METHODS:This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. RESULTS:A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values <0.001). Compared with patients who had received surgery only and non-cancer controls, patients treated with chemotherapy indicated the most altered global brain structural networks, especially in one of properties of small-worldness (p = 0.004). Reduced small-worldness was significantly associated with a lower FACT-Cog total score (r = 0.412, p = 0.024). Increased characteristic path length was also significantly associated with more subjective cognitive impairment (r = -0.388, p = 0.034). CONCLUSION:When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the specific risk factors related to subjective cognitive impairment in the gynaecological cancer population. Such knowledge could inform the development of appropriate treatment and rehabilitation efforts to ameliorate cognitive impairment in gynaecological cancer survivors. 10.1186/s12885-017-3793-4
    Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx. Wagner Lynne I,Gray Robert J,Sparano Joseph A,Whelan Timothy J,Garcia Sofia F,Yanez Betina,Tevaarwerk Amye J,Carlos Ruth C,Albain Kathy S,Olson John A,Goetz Matthew P,Pritchard Kathleen I,Hayes Daniel F,Geyer Charles E,Dees E Claire,McCaskill-Stevens Worta J,Minasian Lori M,Sledge George W,Cella David Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS:Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS:FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were nonsignificant. CONCLUSION:Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk. 10.1200/JCO.19.01866
    Factors associated with cognitive impairment during the first year of treatment for nonmetastatic breast cancer. Rodriguez Nicole,Fawcett Jonathan M,Rash Joshua A,Lester Renee,Powell Erin,MacMillan Connor D,Garland Sheila N Cancer medicine BACKGROUND:Women with breast cancer are more likely to develop cognitive impairment (CI), insomnia, fatigue, and mood disturbance than individuals with other cancers. The main objectives of this study were to establish the prevalence of CI and examine the relationships between CI, insomnia, fatigue, and mood over the first year of breast cancer treatment. METHODS:Participants were recruited after diagnosis and completed validated measures of insomnia, objective and perceived CI, fatigue, and mood disturbance at four time points during the first year of treatment. A random intercepts cross-lagged panel model assessed relationships among symptoms over time. RESULTS:The sample included 98 women. Prevalence of objective CI ranged from 3.1% to 8.2% throughout the year, whereas 36.7% demonstrated a clinically meaningful decline in perceived CI from baseline to 4 months, which remained relatively stable. Greater perceived CI was associated with more fatigue (β = -0.78, z = 17.48, p < .01) and symptoms of insomnia (β = -0.58, z = 5.24, p < .01). Short-term fluctuations in perceived CI (p < .05), but not fatigue or insomnia, predicted future perceived CI. Fatigue (p < .001) was a significant predictor of future reported symptoms of fatigue and insomnia. CONCLUSION:Subjective CI is more prevalent than objective impairments. Fatigue, insomnia, and perceived CI remain stable and are associated during the first year of treatment. Changes in insomnia and fatigue may have little effect on future perceived cognition. Women with breast cancer likely require targeted intervention for these side effects. 10.1002/cam4.3715
    Effects of Acupuncture on Cancer-Related Cognitive Impairment in Chinese Gynecological Cancer Patients: A Pilot Cohort Study. Zeng Yingchun,Cheng Andy S K,Song Ting,Sheng Xiujie,Wang Shaojing,Xie Jianfei,Chan Chetwyn C H Integrative cancer therapies BACKGROUND:Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. METHODS:This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. RESULTS:This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA ( N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture's ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. CONCLUSION:This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment. 10.1177/1534735418777109
    Cognitive Impairment in Patients with Breast Cancer before Surgery: Results from a CANTO Cohort Subgroup. Lange Marie,Hardy-Léger Isabelle,Licaj Idlir,Pistilli Barbara,Rigal Olivier,Le Fel Johan,Lévy Christelle,Capel Aurélie,Coutant Charles,Meyer Jonathan,Lerebours Florence,Petrucci Jean,Vanlemmens Laurence,Brion Marine,Campone Mario,Soulié Patrick,Blain Maxime,Vaz-Luis Ines,Giffard Bénédicte,Martin Anne-Laure,Everhard Sibille,André Fabrice,Dauchy Sarah,Joly Florence Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology BACKGROUND:Twenty to 30% of patients with breast cancer have cognitive impairment after surgery and before adjuvant treatment, but very few studies have focused on cognition before any treatment. This study used a subgroup of women with newly diagnosed breast cancer from the French cancer and toxicities (CANTO) cohort to describe cognition before any treatment in comparison with a group of healthy controls (HC). METHODS:Cognitive assessment was performed before any breast cancer treatment (surgery or neoadjuvant treatment) on women with newly diagnosed invasive stage I-III breast cancer and HCs. Objective cognitive performance, cognitive complaints, anxiety, depression, and fatigue were assessed. Objective cognitive impairment was defined according to International Cognition and Cancer Task Force recommendations. RESULTS:Of the 264 included patients with breast cancer (54 ± 11 years) and 132 age-matched HCs (53 ± 9 years), overall objective cognitive impairment was observed in 28% of patients with breast cancer and 8% of HCs ( < 0.001). Cognitive complaints were reported by 24% of patients versus 12% of HCs ( < 0.01). Patients reported significantly more anxiety and emotional and cognitive fatigue than HCs ( < 0.01). After adjustment, significantly more patients with breast cancer had overall objective cognitive impairment than HCs [OR = 3.01; 95% confidence interval (CI): 1.31-6.88] without significant difference between groups for cognitive complaints (OR = 1.38; 95% CI: 0.65-2.92). Cognitive complaints were positively associated with fatigue (OR = 1.03; 95% CI: 1.02-1.05). CONCLUSIONS:In this prospective study, compared with HCs, patients with localized breast cancer had more objective cognitive impairment before any treatment. Cognitive complaints were mostly related to fatigue. IMPACT:Baseline assessment before treatment is important to assess the impact of each cancer treatment on cognition. 10.1158/1055-9965.EPI-20-0346
    Non-pharmacological interventions for cognitive impairment in women with breast cancer post-chemotherapy: A systematic review. Floyd Ruairí,Dyer Adam H,Kennelly Seán P Journal of geriatric oncology PURPOSE:Cognitive impairment is a well-reported side-effect of chemotherapy in persons with breast cancer. Whilst non-pharmacological interventions have proven efficacious in the management of cognitive impairment in high-risk groups, their efficacy in cognitive impairment post-chemotherapy in patients with breast cancer remains unclear. METHODS:Medline, CINAHL, PsycINFO, Web of Science and Cochrane were searched for randomized controlled trials of non-pharmacological interventions for cognitive impairment post-chemotherapy in women with breast cancer. RESULTS:Of 429 results, 83 full-texts were reviewed with ten meeting inclusion criteria. Interventions included cognitive training, exercise and complementary therapies. The non-pharmacological interventions assessed displayed variable benefits in subjective and/or objective cognitive assessments, with no strong evidence for beneficial effects across included studies. No studies assessed the efficacy of multi-domain interventions. CONCLUSIONS:There is mixed evidence supporting non-pharmacological interventions for cognitive impairment post-chemotherapy in women with breast cancer. Moving forward, multidomain trials combining non-pharmacological interventions are imperative in this high risk cohort. 10.1016/j.jgo.2020.05.012
    Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers. Hshieh Tammy T,Jung Wooram F,Grande Laura J,Chen Jiaying,Stone Richard M,Soiffer Robert J,Driver Jane A,Abel Gregory A JAMA oncology Importance:As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. Objective:To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. Design, Setting, and Participants:This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. Exposures:The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Results:Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). Conclusions and Relevance:These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population. 10.1001/jamaoncol.2017.5674
    Nonpharmacological interventions for cancer-related cognitive impairment in adult cancer patients: A network meta-analysis. Zeng Yingchun,Dong Juntao,Huang Meiling,Zhang Jun-E,Zhang Xiaoming,Xie Man,Wefel Jeffrey S International journal of nursing studies BACKGROUND:Conventional meta-analyses can only provide direct comparison evidence, and the best options of nonpharmacological interventions for cancer-related cognitive impairment remain largely unknown. OBJECTIVES:To evaluate the comparative effects of all known nonpharmacological interventions for cancer-related cognitive impairment, and to rank the best intervention options for adult non- central nervous system cancer patients with cancer-related cognitive impairment. DESIGN:Systematic review with a new analytic approach of network meta-analysis. DATA SOURCES:Six electronic databases were searched for randomized controlled trials from January 2010 to July 2019. REVIEW METHODS:Literature screening, data extraction and quality appraisal was undertaken systematically by two independent reviewers. Quantitative network meta-analysis performed to analyze key study outcomes. The primary outcome was the effectiveness of interventions on subjective cognitive function, and the secondary outcome was the safety of nonpharmacological interventions for cancer-related cognitive impairment. RESULTS:There were 29 eligible randomized controlled trials searched, and a total of 10 interventions identified. All 29 randomized controlled trials that were included had no reported significant adverse events, therefore, these 10 nonpharmacological interventions are safe for cancer-related cognitive impairment management. In terms of effectiveness, the pooled overall effects were in favor of these 10 nonpharmacological interventions. The most effective interventions included meditation, cognitive training, cognitive rehabilitation, and exercise interventions, with a mean difference of effective size plus 95% confidence interval 10.26 (1.53, 19.00), 5.02 (1.41, 8.63), 4.88 (0.65, 9.11), and 3.82 (0.52, 7.13), respectively. Other treatment effects did not show statistically significant differences. CONCLUSIONS:This network meta-analysis found that meditation interventions, cognitive training, cognitive rehabilitation, and exercise were the most effective interventions for adult non-central nervous system cancer patients to manage cancer-related cognitive impairment. Results of this network meta-analysis contribute evidence-based data to inform medical decision-making. 10.1016/j.ijnurstu.2019.103514
    Cancer-related cognitive impairment (CRCI), depression and quality of life in gynecological cancer patients: a prospective study. De Rosa Nicoletta,Della Corte Luigi,Giannattasio Alessia,Giampaolino Pierluigi,Di Carlo Costantino,Bifulco Giuseppe Archives of gynecology and obstetrics PURPOSE:Cancer-related cognitive impairment (CRCI) has been reported in non-central nervous system neoplasms survivors. The purpose of this study was to evaluate the perception of cognitive decrement in patients undergoing surgical and / or medical therapy for gynecological cancers. METHODS:All women diagnosed with primary gynecological cancer and undergoing active medical treatment have been enrolled in a prospective study. Before starting treatment (T1) and 6 months after the end of treatment (T2), patients were interviewed to evaluate the effects of cancer treatment on perceived cognitive function (using FACT-Cog -version 3), on depression (using Beck Depression Inventory-II test) and on quality of life (using EORTC-QLQC-30). Age, education level, marital status, lifestyle, menopausal state at diagnosis, cancer type, cancer FIGO stage, treatment modality was also recorded. The differences between baseline and post-treatment results have been evaluated with Student's t test. The results have been stratified by the menopausal state at diagnosis, type of tumor (endometrial, cervical, ovarian, vulvar) disease stage and type of treatment (chemotherapy or radiotherapy). RESULTS:Seventy-three patients were included. A significant reduction in perceived cognitive impairments was demonstrated at T2 (CogPCI: 61.35 ± 13.83 vs 55.05 ± 16.56; p < 0.05). On the contrary, a significant improvement was shown in depression state (BDII: 21.14 ± 11.23 vs 12.82 ± 12.33, p < 0.005). The menopausal state at surgery, tumor site, stage and treatment modality seem to influence the variables analyzed. CONCLUSION:CRCI is a true risk also in gynecological cancer survivors. The cognitive impairment does not seem to be dependent on depression state after treatment or to a menopausal condition. Assessing cognitive decline in cancer survivorship is essential for ensuring the optimum quality of life and functioning. 10.1007/s00404-020-05896-6
    Determination of Cytokines and Oxidative Stress Biomarkers in Cognitive Impairment Induced by Methylmalonic Acidemia. Li Qiliang,Jin Hong,Liu Ying,Rong Yu,Yang Tana,Nie Xiaolu,Song Wenqi Neuroimmunomodulation OBJECTIVE:Methylmalonic acidemia (MMA) is the most common organic acidemia in children. Many patients with MMA suffered from cognitive impairments. The aim of this study was to identify the significance of cytokines and oxidative stress biomarkers in MMA-induced cognitive impairment. METHODS:We enrolled 64 children with combined MMA and homocystinuria and 64 age- and sex-matched healthy volunteers. Participants were subsequently classified as with or without cognitive impairments using a uniform neuropsychological assessment test. Serum samples were collected. The serum levels of cytokines and oxidative stress biomarkers were measured using the ELISA or chemical methods. RESULTS:Compared to control group, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA), and nitric oxide (NO) in the MMA patients increased markedly (p < 0.05); glutathione (GSH) and superoxide dismutase (SOD) decreased obviously (p < 0.01). The levels of IL-6, TNF-α, NO, and MDA in the serum were negatively associated with DQ or IQ scores. The levels of GSH and SOD in the serum were positively correlated with DQ or IQ scores. After receiver operating characteristic curve analysis, NO was the most useful individual marker for distinguishing the cognitive dysfunction, corresponding to the area under ROC curve (AUC) of 0.82 (95% CI, 0.74-0.91), sensitivity of 76.60%, and specificity of 80.25%. GSH and MDA were also useful for diagnosis of MMA-induced cognitive dysfunction, corresponding to the AUC of 0.80 (95% CI, 0.70-0.89), and 0.73 (95% CI, 0.63-0.82), respectively. The sensitivity and specificity of GSH were 72.34 and 80.25%, respectively. The sensitivity and specificity of MDA were 85.11 and 51.85%, respectively. CONCLUSIONS:The high-concentration methylmalonic acid in the blood induced immune cells to release pro-inflammatory cytokines such as TNF-α and IL-6. These cytokines and high-concentration methylmalonic acid stimulated the immune cells to produce reactive oxygen species (ROS) and reactive nitrogen species (RNS). The serum methylmalonic acid, cytokines, ROS, and RNS were across the blood-brain barrier and induced cognitive impairment. The small molecule substances such as serum NO, MDA, and GSH participated in the process of neuroinflammation and oxidative stress injury induced by MMA and could be useful for distinguishing the cognitive impairment. 10.1159/000511590
    Screening for cognitive impairment in older adults with hematological malignancies using the Montreal Cognitive Assessment and neuropsychological testing. Koll Thuy T,Sheese Amelia Nelson,Semin Jessica,Ernst Weston,High Robin,Wildes Tanya M,Fisher Alfred,Murman Daniel L Journal of geriatric oncology OBJECTIVES:The primary objective of the current study is to describe the prevalence and profile of cognitive domains affected in older adults with hematological malignancies evaluated for hematopoietic cell transplantation (HCT) using the Montreal Cognitive Assessment (MoCA) and neuropsychological tests. The secondary objective is to determine if a specific MoCA cut-off score would correlate with the identification of cognitive impairment detected by neuropsychological tests. This would facilitate interpretation of cognitive screening and referral of patients who would likely need further neuropsychological testing. MATERIALS AND METHODS:Fifty-one patients 60 years and older who were evaluated for HCT were assessed using a battery of standardized neuropsychological tests and MoCA. We analyzed Receiver Operating Characteristics (ROC) comparing MoCA scores and four different neuropsychological test criteria for cognitive impairment. RESULTS:The prevalence of cognitive impairment detected by neuropsychological tests was 53 to 70.6% using the criteria for patients with cancer by the International Cancer Cognition Task Force (ICCTF). The following cognitive domains were most affected: language, learning and memory, visuospatial skills, and executive function. MoCA is an appropriate screening test for cognitive impairment. Using the ICCTF criteria, 86 to 100% of patients are correctly classified as having significant cognitive impairment on neuropsychological tests using a cut-off score of 20 or less. CONCLUSION:There is a high prevalence of cognitive impairment identified by neuropsychological tests in older patients with hematological malignancies evaluated for HCT. Identification of an appropriate MoCA cut-off score in this population is important to identify patients who would benefit from further assessment. 10.1016/j.jgo.2019.11.007
    Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Lange M,Joly F,Vardy J,Ahles T,Dubois M,Tron L,Winocur G,De Ruiter M B,Castel H Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN:This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS:Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS:CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer. 10.1093/annonc/mdz410
    Mild cognitive impairment in long-term brain tumor survivors following brain irradiation. Cramer Christina K,McKee Neil,Case L Doug,Chan Michael D,Cummings Tiffany L,Lesser Glenn J,Shaw Edward G,Rapp Stephen R Journal of neuro-oncology INTRODUCTION:There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer's Association (NIA-AA). METHODS:We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md). RESULTS:One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI. CONCLUSION:Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles. 10.1007/s11060-018-03032-8
    The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α. Ren Xiaojia,Keeney Jeriel T R,Miriyala Sumitra,Noel Teresa,Powell David K,Chaiswing Luksana,Bondada Subbarao,St Clair Daret K,Butterfield D Allan Free radical biology & medicine Cancer treatments are developing fast and the number of cancer survivors could arise to 20 million in United State by 2025. However, a large fraction of cancer survivors demonstrate cognitive dysfunction and associated decreased quality of life both shortly, and often long-term, after chemotherapy treatment. The etiologies of chemotherapy induced cognitive impairment (CICI) are complicated, made more so by the fact that many anti-cancer drugs cannot cross the blood-brain barrier (BBB). Multiple related factors and confounders lead to difficulties in determining the underlying mechanisms. Chemotherapy induced, oxidative stress-mediated tumor necrosis factor-alpha (TNF-α) elevation was considered as one of the main candidate mechanisms underlying CICI. Doxorubicin (Dox) is a prototypical reactive oxygen species (ROS)-generating chemotherapeutic agent used to treat solid tumors and lymphomas as part of multi-drug chemotherapeutic regimens. We previously reported that peripheral Dox-administration leads to plasma protein damage and elevation of TNF-α in plasma and brain of mice. In the present study, we used TNF-α null (TNFKO) mice to investigate the role of TNF-α in Dox-induced, oxidative stress-mediated alterations in brain. We report that Dox-induced oxidative stress in brain is ameliorated and brain mitochondrial function assessed by the Seahorse-determined oxygen consumption rate (OCR) is preserved in brains of TNFKO mice. Further, we show that Dox-decreased the level of hippocampal choline-containing compounds and brain phospholipases activity are partially protected in TNFKO group in MRS study. Our results provide strong evidence that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as phospholipases changes decreased in the CNS are associated with oxidative stress mediated by TNF-α. These results are consistent with the notion that oxidative stress and elevated TNF-α in brain underlie the damage to mitochondria and other pathological changes that lead to CICI. The results are discussed with reference to our identifying a potential therapeutic target to protect against cognitive problems after chemotherapy. 10.1016/j.freeradbiomed.2018.12.029
    Cognitive impairment in older adults with cancer. Lloyd-Williams Mari,Mogan Caroline,Harrison Dening Karen Current opinion in supportive and palliative care PURPOSE OF REVIEW:Cognitive impairment is increasing in an ageing population and as people live longer, they are more likely to develop cancer therefore cognitive impairment and cancer are frequently co-occurring. We reviewed articles published since 2018 on cognitive impairment and cancer. RECENT FINDINGS:The current review has focused on diagnosis, treatment and palliative and end of life care. A comprehensive systematic review reported joint cancer and cognitive impairment prevalence from 0.2 to 45.6%. The review reported there was reduced likelihood of patients with co-occurring cognitive and cancer receiving information regarding cancer stage, reduced cancer treatment with curative intent and limited pain and symptom management. Further studies emphasized the role of family carers in supporting patients with cognitive impairment through cancer treatment. SUMMARY:Disappointingly in an area where the numbers of patients with cognitive impairment and cancer are increasing, there appears to be little recently published research in this area. We conclude that further research is required to determine how best to support patients with cognitive impairment and cancer and families during diagnosis of cancer, treatment and continuing care and most importantly the findings of all studies are implemented within clinical practice. 10.1097/SPC.0000000000000534
    Prevalence of cognitive impairment and change in patients with breast cancer: A systematic review of longitudinal studies. Dijkshoorn Aicha B C,van Stralen Haike E,Sloots Maurits,Schagen Sanne B,Visser-Meily Johanna M A,Schepers Vera P M Psycho-oncology OBJECTIVE:Patients with breast cancer face cognitive impairment that affects their quality of life; partially attributable to treatment. Our aim was to detail the prevalence and change of cognitive impairment during the course of treatment. We also investigated the effect of therapy (chemotherapy [CT]) vs. radiotherapy and/or endocrine therapy vs. healthy controls). METHODS:This article reviews longitudinal cohort studies published to date in Medline and Embase that (i) assess cognition before and after therapy, (ii) report prevalence cognitive impairment or change, and (iii) use standardized and valid neuropsychological tests. We used the original authors' criteria for cognitive impairment. RESULTS:The title and abstract of 891 articles were screened, resulting in the identification of 90 potentially relevant articles while applying the eligibility criteria. After full-text examination, 17 studies were included. Prevalence of cognitive impairment range from 25% before therapy, through 24% after therapy to 21% at maximal 1-year follow-up (FU). Compared to their pretreatment cognitive functioning, 24% of patients decline after treatment and 24% at 1-year FU. Some studies also reported cognitive improvement showing that 15% and 31% of patients improve, respectively. In general, patients undergoing CT have a higher chance of cognitive impairment and decline than no-CT patients and healthy controls. CONCLUSIONS:This study shows that one out of four breast cancer patients shows cognitive impairment prior to treatment administration CT and a significant number of patients decline during the course of disease, suggesting that cognitive impairment is not exclusively related to CT and/or no-CT therapies. This study shows that assessment of cognitive functioning, ideally over time, is crucial and may help the implementation of personalized rehabilitation pathways. 10.1002/pon.5623
    Mild to Moderate Cognitive Impairment Does Not Affect the Ability to Self-Report Important Symptoms in Patients With Cancer: A Prospective Longitudinal Multinational Study (EPCCS). Ekström Magnus P,Palmqvist Sebastian,Currow David C,Sjøgren Per,Kurita Geana P,Jakobsen Gunnhild,Kaasa Stein,Hjermstad Marianne Journal of pain and symptom management CONTEXT:Patients with advanced cancer commonly suffer from both distressing symptoms and cognitive impairment, but the effect of cognitive impairment on the reliability and validity of symptom self-report is unknown. OBJECTIVES:To evaluate the reliability and validity of symptom self-report in cancer outpatients with and without mild to moderate cognitive impairment. METHODS:This was an analysis of the longitudinal European Palliative Care Cancer Symptom study of adults with incurable cancer in specialized palliative care (30 centers across 12 countries). Patients who could not comply with the study because of severe cognitive impairment were excluded. Cognitive status on the Mini-Mental State Examination short version and nine symptoms (pain, tiredness, drowsiness, nausea, appetite, breathlessness, depression, anxiety, and well-being) using the revised Edmonton Symptom Assessment System were self-reported at baseline and one-month follow-up. Reliability was analyzed using intraclass correlation coefficients and validity using regression of each symptom with health-related quality of life (HrQoL) measured with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care. RESULTS:A total of 1047 patients were included: mean age of 62.9 years; 54.4% women; main cancer types were of digestive organs (26.6%), breast (21.6%), and lungs (21.2%). Cognitive impairment was present in 181 (17.3%) at baseline and associated with worse self-reported tiredness, drowsiness, appetite, and depression. Reliability (intraclass correlation coefficient) and validity (associations with HrQoL) were similar between people with/without cognitive impairment across the nine symptoms, except breathlessness, which showed a weaker relation to HrQoL in patients with cognitive impairment. Findings were robust in sensitivity analyses and after controlling for potential confounders. CONCLUSION:In advanced cancer, self-report of nine major symptoms was reliable and valid also in people with mild-to-moderate cognitive impairment. TRIAL REGISTRATION:ClinicalTrials.gov database (NCT01362816). 10.1016/j.jpainsymman.2020.03.007
    Risk Factors for Cognitive Impairment in High-Grade Glioma Patients Treated with Postoperative Radiochemotherapy. Wang Qiang,Xiao Fengxia,Qi Fei,Song Xiaopeng,Yu Yonghua Cancer research and treatment : official journal of Korean Cancer Association PURPOSE:Fractionated radiotherapy as well as concomitant and adjuvant chemotherapy such as temozolomide for postoperative high-grade glioma (HGG) patients improves progression-free survival and overall survival. Multiple factors such as chemotherapy, radiotherapy, tumor grade, residual tumor volume, and genetic modifications might play a role in the formation of cognitive impairment. The risk factors of cognitive impairment in postoperative patients with HGG receiving radiotherapy and chemotherapy remains a concern in this population. The purpose of this study was to identify risk factors for cognitive impairment in patients of postoperative HGG. MATERIALS AND METHODS:A total of 229 patients with HGG who underwent surgery were analyzed. Cognitive impairment was defined as a decrease of Cognitive Assessment Montreal (MoCA)'s score in at least two cognitive domains or any MoCA's score of less than 26 points at the time of study compared with baseline level. Multiple potential risk factors including methylated status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, glioma World Health Organization (WHO) grade, residual tumor volume, education, and sex were analyzed. Cox univariate and multivariate regression analysis was used to detect the significant risk factors for cognitive impairment. RESULTS:At the end of follow-up among the 229 patients, 147 patients (67%) developed cognitive impairment. 82 patients (36%) remained in normal cognitive condition. In multivariate analysis, unmethylated MGMT promoter (hazard ratio [HR], 1.679; 95% confidence interval [CI], 1.212 to 2.326; p=0.002), glioblastoma (HR, 1.550; 95% CI, 1.117 to 2.149; p=0.009), and residual tumor volume > 5.58 cm3 (HR, 1.454; 95% CI, 1.047 to 2.020; p=0.026) were independent risk factors for cognitive impairment. CONCLUSION:Methylated status of the MGMT promoter, glioma WHO grade, and residual tumor volume might be risk factors for the cognitive impairment in postoperative patients with HGG. 10.4143/crt.2019.242
    Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems. Gutenkunst Shannon L,Vardy Janette L,Dhillon Haryana M,Bell Melanie L Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer OBJECTIVE:Cognitive impairment negatively affects some cancer survivors who have completed chemotherapy; however, factors underlying this cognitive impairment remain poorly understood. We aimed to investigate (1) the relative importance of demographics, medical, and psychological characteristics associated with cognitive impairment and (2) the specific variables associated with cognitive impairment in adult cancer survivors who completed adjuvant chemotherapy. METHODS:We performed post hoc analyses of baseline data from early-stage cancer survivors with cognitive complaints who received adjuvant chemotherapy 0.5-5 years earlier and volunteered for a trial designed to improve cognition. The primary outcome of self-reported cognitive impairment was measured using a questionnaire; secondary outcome of objective cognitive impairment was measured using a computerized neuropsychological test battery. Hierarchical linear regression determined the relative importance of demographics, medical, and psychological characteristics in associations with both self-reported and objective cognitive impairment. RESULTS:The sample was 95% female and 89% breast cancer patients. The final model accounted for 33% of variation in self-reported cognitive impairment (n = 212, demographics 5%, medical 3%, and psychological 25%), with fatigue and stress as significant individual correlates (p values ≤ 0.0001). For the secondary analysis, the final model accounted for 19% of variation in objective cognitive impairment (n = 206, demographics 10%, medical 5%, and psychological 4%), with age, smoking history, and number of chemotherapy cycles as significant individual correlates. CONCLUSION:We found that psychological characteristics are more important than demographic and medical characteristics in self-reported cognitive impairment, whereas other characteristics are more important in objective cognitive impairment. This suggests clinicians should investigate possible psychological problems in cancer survivors who self-report cognitive impairment. 10.1007/s00520-020-05616-5
    Handgrip strength, tumor necrosis factor-α, interlukin-6, and visfatin levels in oldest elderly patients with cognitive impairment. Huang Hsien-Hao,Chang Julia Chia-Yu,Liu Hui-Chia,Yang Zhi-Yu,Yang Yu-Jie,Chen Liang-Kung,Yen David Hung-Tsang Experimental gerontology INTRODUCTION:Handgrip strength is associated with mild cognitive impairment. Tumor necrosis factor [TNF]-α and interleukin [IL]-6 were pro-inflammatory cytokines influencing the severity of initial neurological deficit. Visfatin is a novel adipokine and has a strong correlation with inflammation. The relationships of TNF-α, IL-6 and visfatin are not consistent, and no study has investigated them in the elderly patients with cognitive impairment. METHODS:This study included patients aged ≥75 years at the emergency department from August 2018 to February 2019. All patients underwent comprehensive geriatric assessment and blood tests for fasting plasma TNF-α, IL-6 and visfatin levels. RESULTS:We enrolled 106 elderly patients with a mean age of 87.3 years, including 62 (58.4%) patients in cognitive impairment group (Mini-Mental State Examination [MMSE] < 24) and 44 (41.5%) patients in the non-cognitive impairment group. Compared to the non-cognitive impairment group, the cognitive impairment group had significantly lower handgrip strength, and significantly higher TNF-α, IL-6 and visfatin levels. TNF-α positively correlated with IL-6. Both TNF-α and IL-6 negatively correlated with Barthel index and MMSE. Handgrip strength negatively correlated with TNF-α but positively correlated with Barthel index and MMSE scores. Backward and stepwise multiple logistic regression analyses showed that the independent predictor for cognitive impairment was handgrip strength and age. CONCLUSION:The cognitive impairment group had significantly higher serum TNF-α, IL-6, and visfatin levels. The independent predictors of cognitive impairment were handgrip strength and age. Handgrip strength negatively correlated with TNF-α and IL-6 but positively with Barthel index and MMSE scores. 10.1016/j.exger.2020.111138
    Neuronal autoantibodies associated with cognitive impairment in melanoma patients. Bartels F,Strönisch T,Farmer K,Rentzsch K,Kiecker F,Finke C Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Cancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction. PATIENTS AND METHODS:A total of 157 consecutive melanoma patients with a median age of 63 years were recruited at the Department of Dermatology, Charité-Universitätsmedizin Berlin and tested for neuronal autoantibodies. A comprehensive neuropsychological assessment was carried out in a selected subgroup of 84 patients after exclusion of patients with confounding factors for a cognitive dysfunction, including brain metastases, relevant medication, and neurological disorders. RESULTS:Neuronal autoantibodies were found in 22.3% of melanoma patients. The most frequent antibodies were IgA/IgM anti-NMDAR antibodies. Applying the International Cognition and Cancer Task Force criteria, 36.9% had cognitive impairment, however, with a threefold higher odds in antibody-positive compared with antibody-negative patients (57.1% versus 30.2%, OR = 3.1, 95% CI: 1.1 to 8.6; P = 0.037). In patients with anti-NMDAR antibodies, this impairment increased with higher antibody titers (P = 0.007). Antibody-positive patients had a significantly impaired overall cognitive performance (z-value: -0.38 ± 0.69 versus 0.00 ± 0.56; P = 0.014) as well as significant impairments in tests of memory, attention, and executive function. In a multiple linear regression analysis, autoantibodies were an independent risk factor for cognitive impairment (B = -0.282; 95% CI: -0.492 to -0.071; P = 0.009). Autoantibody seropositivity was associated with immune checkpoint inhibitor treatment and a history of autoimmune diseases. CONCLUSIONS:A large number of melanoma patients harbor neuronal autoantibodies that are associated with significant cognitive impairment affecting memory, attention, and executive function. Neuronal autoantibodies might represent a pathophysiological factor and possible biomarker in the development of cancer-related cognitive impairment. 10.1093/annonc/mdz083
    Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in patients with newly diagnosed prostate cancer referred to androgen-deprivation therapy. R Buskbjerg Cecilie,Zachariae Robert,Buus Simon,H Gravholt Claus,Haldbo-Classen Lene,Hosseini S M Hadi,Amidi Ali Cancer BACKGROUND:Evidence suggests that patients with prostate cancer (PCPs) receiving androgen-deprivation therapy (ADT) are at risk for cognitive impairment. Research with other populations with cancer indicates that cognitive impairment may also occur before systemic treatment. The authors assessed cognitive impairment in untreated PCPs referred to ADT and explored associations with structural brain networks, endocrine status, and selected genotypes. METHODS:Forty untreated PCPs and 27 healthy controls (HCs) who completed a questionnaire package underwent neuropsychological testing, magnetic resonance imaging, and blood sampling. Cognitive impairment was defined as a z score ≤-2 on 1 neuropsychological test or ≤-1.5 on 2 neuropsychological tests. Structural brain networks were investigated using diffusion-weighted imaging and graph theory. Associations of cognitive performance with patient-reported outcome measures (PROMs), brain networks, testosterone levels, and genotypes (apolipoprotein ε [APOE], catechol-O-methyltransferase [COMT], and brain-derived neurotrophic factor [BDNF]) were explored. RESULTS:PCPs performed poorer than HCs on 7 of 15 neuropsychological tests and exhibited a higher frequency of cognitive impairment (57.5% vs 22.2%; P ≤ .01 to .03). All neuropsychological outcomes were associated with ≥1 PROM (P ≤ .01 to .04). Compared with the HC group, the PCP group exhibited altered global network organization as well as disrupted regional network characteristics in frontal and temporal regions (P < .01). PCPs had lower testosterone levels (P < .01) than HCs, which correlated with better visuospatial performance (r = -0.33; P = .04). No effects were found of APOE, COMT, or BDNF. CONCLUSIONS:The current results suggest that untreated PCPs may demonstrate cognitive impairment and that psychological and behavioral symptoms (PROMs), as well as impairment in structural brain networks, might be the underlying mechanisms. 10.1002/cncr.33387