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Background: Apolipoprotein Ɛ4 genotype (APOE4) has been associated with cancer-related cognitive impairment, but its interaction with treatments remains unclear. This longitudinal study aims to evaluate the association between APOE4 and cognitive impairment in women with breast cancer (BC) undergoing chemotherapy (CT) or endocrine therapy (ET)., Findings: Patients with stage I-III breast cancer completed cognitive tests at diagnosis (before surgery), then at year-1, year-2, and year-4 post-diagnosis. APOE4 status (APOE4+ [carriers] vs. APOE4- [non-carriers]) was genotyped from blood sample. Cognitive outcomes included episodic memory, working memory, attention, processing speed, and executive functions. Patients were defined as having overall cognitive impairment if ≥ 2 domains were impaired. We fitted logistic and linear mixed models to assess associations of APOE4 status with cognitive impairment over time and interactions of APOE4 with CT and ET. Among 334 patients, 64 (19%) were APOE4+, 117 (35%) patients were treated with CT, 41 (12%) with ET, and 162 (49%) with CT+ET. There were no significant association between overall cognitive impairment and APOE4, nor interactions with CT or ET. At year-4, APOE4+ patients treated with ET had lower attention performance than APOE4- patients not treated with ET, and APOE4+ patients not treated with ET had lower episodic memory performance than APOE4- patients not treated with ET., Conclusions: This study suggests APOE4 genotyping is ineffective for detecting cognitive impairment in BC. New genotypes should be identified to predict cognitive decline in BC., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided written informed consent and the study was approved by the ethics committee (ID-RCB:2011-A01095-36,11-039). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Cancer-related cognitive impairment (CRCI) is under-addressed by healthcare professionals owing to a lack of clinical management guidelines. This European Delphi study proposes recommendations to healthcare professionals for the management of CRCI in patients with non-central nervous system (non-CNS) cancers., Methods: Twenty-two recommendations were developed based on a literature review and authors' clinical experience, split into three categories: screening, cognitive assessment, intervention. The survey included European professionals, experts in CRCI. The Delphi method was used: experts rated the clinical relevancy of recommendations on a 9-point Likert scale in three rounds. A recommendation was accepted if all votes were between 7 and 9. Recommendations not accepted in round 1 and round 2 were deleted, or modified and rated in round 3., Results: Eighteen professionals (psychologists, physicians, researchers) voted and accepted 15 recommendations. Experts recommended the systematic screening of CRCI, followed by a short objective cognitive assessment, if complaints screened. A comprehensive evaluation is recommended if CRCI persists 6 months post-treatment. Cognitive rehabilitation, physical activity, meditative-movement therapy, and multimodal intervention should be offered. Recommendations about frequency and duration of interventions, the professional to administer cognitive rehabilitation and the use of meditation and cognitive training without psychoeducation were not accepted., Conclusions: This survey provides 15 recommendations to assist healthcare professionals in detecting, assessing and offering interventions for CRCI., Implications for Cancer Survivors: These recommendations should be included in supportive care to help healthcare professionals to detect CRCI and propose the best available intervention for patients with cognitive complaints. Developing CRCI management in clinical settings would improve patients' quality of life., (© 2023. The Author(s).)

Background: Inflammation could be related to cancer-related cognitive impairment (CRCI) and might be used as a predictive marker of long-term CRCI. We evaluated associations between inflammatory markers assessed at diagnosis of breast cancer and CRCI two years afterwards., Methods: Newly diagnosed stage I-III patients with breast cancer from the French CANTO-Cog (Cognitive sub-study of CANTO, NCT01993498) were included at diagnosis (baseline). Serum inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, CRP) were assessed at baseline. Outcomes at year 2 post-baseline included overall cognitive impairment (≥ 2 impaired domains) and the following domains: episodic memory, working memory, attention, processing speed, and executive functions. Multivariable logistic regression models evaluated associations between markers and outcomes, controlling for age, education, and baseline cognitive impairment., Results: Among 200 patients, the mean age was 54 ± 11 years, with 127 (64%) receiving chemotherapy. Fifty-three (27%) patients had overall cognitive impairment at both timepoints. Overall cognitive impairment at year 2 was associated with high (> 3 mg/L) baseline CRP (OR = 2.84, 95%CI: 1.06-7.64, p = 0.037). In addition, associations were found between high CRP and processing speed impairment (OR = 2.47, 95%CI:1.05-5.87, p = 0.039), and between high IL-6 and episodic memory impairment (OR = 5.50, 95%CI:1.43-36.6, p = 0.010)., Conclusions: In this cohort, high levels of CRP and IL-6 assessed at diagnosis were associated with overall CRCI, processing speed and episodic memory impairments two years later. These findings suggest a potential inflammatory basis for long-term CRCI. CRP may represent an easily measurable marker in clinical settings and be potentially used to screen patients at greater risk of persistent CRCI., (© 2024. The Author(s).)

Background: Elderly cancer patients often experience cognitive difficulties that can affect their quality of life and autonomy. However, they are rarely included in clinical trials, and only one study has explored the feasibility of cognitive training in this population. While digital cognitive training has been successful in improving cognition in younger patients, its feasibility in elderly patients requires evaluation., Objectives: This feasibility study primarily focused on evaluating patients' ability to use digital cognitive stimulation (usability). Secondary objectives were to evaluate acceptability, adherence, and satisfaction with regard to digital cognitive stimulation in elderly breast cancer patients., Methods: Elderly breast cancer patients at least 70 years old who were receiving cancer treatment (chemotherapy, targeted therapy, and/or radiotherapy) were recruited. Cognitive complaints were evaluated at baseline using the Functional Assessment of Cancer Therapy-Cognitive Function scale (FACT-Cog). Participants were invited to attend three 20-minute sessions of digital cognitive stimulation using HappyNeuron PRESCO software App on tablets, with the first session being supervised by a neuropsychologist and the two others being performed independently either at home or at the cancer center. We hypothesized that participants would spend 10 of the 20 min of the given time with the tablet completing exercises (training time). Thus, the usability of digital cognitive stimulation was defined as completing at least three exercises during the training time (10 min) of one of the two training sessions in autonomy. The proportion of patients who agreed to participate (acceptability) and completion of planned sessions (adherence) were also estimated. Satisfaction was evaluated post-intervention through a self-report questionnaire., Results: 240 patients were initially screened, 60% (n = 145) were eligible and 38% agreed to participate in the study. Included patients (n = 55) had a mean age of 73 ± 3 years, 96% an ECOG score of 0-1 and were undergoing radiotherapy (64%), and/or chemotherapy (47%) and/or targeted therapy (36%) for stage I-II breast cancer (79%). Most patients reported significant cognitive complaints (82%) and 55% had previous experience with digital tools (n = 30). The usability rate was 92%, with 46 out of 50 evaluable participants completing at least three exercises during the training time. The adherence rate was 88%, with 43/50 participants completing all planned sessions. Participants were largely satisfied with the cognitive intervention format (87%). They preferred to complete sessions at the cancer center under the supervision of the neuropsychologist than alone at home (90%)., Conclusions: The high level of usability, adherence and satisfaction in this study shows for the first time the feasibility of digital cognitive stimulation in cancer patients older than 70 years. However, the intervention should be proposed only to patients reporting cognitive complaints and should be structured and supervised to improve acceptability and adherence., Trial Registration: ClinicalTrials identifier: NCT04261153, registered on 07/02/2020., (© 2024. The Author(s).)

Introduction: Cancer-related cognitive decline (CRCD) is often reported by patients with non-central nervous system (non-CNS) cancers. Since it can affect by the patient's quality of life and can last for several years after cancer treatment, interventions seeking to alleviate this decline should be developed. Despite research studies on this topic, interventions for CRCD in clinical practice are scarce., Areas Covered: This narrative review provides the state of the art on non-pharmacological interventions for CRCD in patients with non-CNS cancers., Expert Opinion: Non-pharmacological interventions, such as cognitive, physical and mind-body interventions seem effective in reducing CRCD. Future research should not only evaluate the efficacy of interventions but also the barriers and facilitators affecting the implementation of interventions in clinical settings. In particular, the acceptability of the intervention, its feasibility, adherence and fidelity to the initial protocol should be evaluated. Agreement is also required regarding the length and intensity of the intervention. Moreover, future studies should compare the efficacy of interventions with active control groups, rather than using only a waitlist control group. Finally, multimodal interventions focused on the multidimensionality of CRCD and associated factors such as psychological factors, fatigue and quality of sleep would pave the way for more holistic forms of patient management.

Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs., Competing Interests: Conflict of interest None of the authors has conflict of interest related to the content of this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Previous studies have revealed both sleep alterations and prospective memory (PM) impairments in breast cancer (BC) patients. PM refers to memory of intended actions and is crucial for daily living tasks and treatment compliance. As sleep is known to favor memory consolidation, one may expect that changes in sleep quality related to BC would have an impact on PM performance. This study aimed at assessing sleep-dependent consolidation of intentions using an ecological, virtual reality-based PM task in BC patients not treated with chemotherapy., Materials and Methods: Thirty-seven early stages BC patients and 21 healthy controls (HC) participated in this study. PM was assessed using a virtual reality task, during which participants learnt a list of intentions and recalled them after a retention interval filled with a day awake or a night of sleep monitored by polysomnography. Sleep spindles and slow waves, brain oscillations involved in sleep-dependent memory consolidation, were quantified automatically using the Aseega software (Physip). Subjective sleep disturbances and markers of quality of life (psychological distress, fatigue, and well-being) were assessed by questionnaires., Results: Greater PM performance was observed after sleep than after an equivalent period of daytime wakefulness for both groups (HC and BC). PM performance after sleep did not differ significantly between groups. Yet, BC patients reported greater sleep disturbances than HC which were related with poorer intentions retrieval, greater psychological distress, fatigue and poorer well-being. The frequency of spindles was higher and the amplitude of slow waves lower in BC patients compared to HC. However, no significant association was observed between polysomnography parameters and PM scores in the whole sample of participants., Conclusion: Although subtle changes in brain oscillations involved in sleep-dependent memory consolidation were observed, these changes did not significantly impair overnight PM consolidation in BC patients. Nevertheless, poorer PM performance was associated with greater sleep complaints which in turn were related to poorer quality of life. Overall, these data suggest that sleep-dependent PM consolidation mechanisms are not altered in early stages BC patients not treated with chemotherapy. Further investigations are needed to understand the association between markers of quality of life and sleep-dependent memory consolidation., Competing Interests: CB has ownership/directorship and was employed by Physip, who owns Aseega. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duivon, Perrier, Segura-Djezzar, Joly, Rehel, Berthomier, Grellard, Clarisse, Geffrelot, Emile, Lévy, Viader, Eustache, Desgranges, Rauchs and Giffard.)

Patients with non-central nervous system (CNS) cancer frequently report cognitive complaints, that are recurrent and affect their quality of life. In order to improve supportive care of these cognitive difficulties, it is important to identify associated factors. Sleep disturbance is a good candidate to study, as patients with non-CNS cancer frequently report sleep disorders, and sleep plays a key role in cognitive functioning. The objective of the present systematic review was to summarize the results of studies evaluating the relationship between cognition and sleep in non-CNS cancer, and to highlight the need for further studies. PubMed [Medline] and Scopus databases were screened from April to November 2020 for studies published in English evaluating the association between cognition and sleep in adults with non-CNS cancer. The characteristics and risk of bias for each of the 30 included studies have been reported. Greater cognitive complaints in patients with non-CNS cancer were related to poorer self-reported sleep quality in almost all studies (n = 22/24). By contrast, around half of the studies reported a significant association between poorer neuropsychological performances and sleep complaints (n = 5/11). The studies were found to have several limitations, such as the lack of a control group, which would have shed the light on the period of occurrence of this association (e.g. after cancer diagnosis or after cancer treatments). Our review also identified factors that may influence the relationship between cognition and sleep. Recommendations are given for improving the methodology of future studies and extending the impact of their results., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rest-activity rhythm (RAR) disruptions are frequently associated with chemotherapy in breast cancer (BC), but they are less known in BC with endocrine therapy (ET). The aim of this ancillary study was to characterize the RAR and estimated sleep characteristics from actigraphy in BC patients either treated (ET+) or untreated with ET (ET-), compared to healthy controls (HC) and using a cross-sectional design. Eighteen ET+, 18 ET-, and 16 HC completed questionnaires and wore wrist actigraphs at home for 2 weeks. Parametric and nonparametric RAR, sleep parameters, and quality of life were compared between groups (p < .05). BC groups presented lower daytime activity than HC according to RAR analysis (mesor and M10 parameters). Compared to HC, ET- had lower inter-daily stability and ET+ had greater sleep complaints. Compared to ET-, ET+ had lower sleep efficiency, more time awake, and higher activity levels at night, as assessed with actigraphy. Our results suggest an effect of cancer independent of treatment on RAR in BC, highlighting the need for further investigation of this topic. In contrast, sleep as assessed with actigraphy seems modified only during ET which matches with patients' sleep complaints. Further longitudinal studies would aid in confirming the latter hypothesis., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT., Methods: PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography., Discussion: This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy., Trial Registration: NCT03420105 , registered: January 10, 2018.