Inflammation at diagnosis and cognitive impairment two years later in breast cancer patients from the Canto-Cog study.

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.

Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta-analysis.

BACKGROUND: Hormone therapy, which is widely prescribed for prostate cancer, might induce cognitive impairment and affect the autonomy of elderly patients. However, previous studies provided conflicting results. The aim of this systematic review and meta-analysis was to synthesize the longitudinal impact of hormone therapy on objective (cognitive tests) and subjective (questionnaires) cognition. METHODS: A search was performed of the PubMed, Web of Science, and PsycINFO databases. Studies that longitudinally assessed cognition in patients undergoing androgen-deprivation therapy and new-generation hormone therapy were considered. To perform a meta-analysis, available scores were aggregated and classified into six objective domains and one subjective domain. Weighted mean effect sizes were computed using a random effect model. RESULTS: Twenty studies were included in the systematic review (1440 patients), and 15 could be included in the meta-analysis (1093 patients). In the systematic review, 20%-50% of patients had objective cognitive impairment before treatment initiation. The meta-analysis revealed a decline in subjective cognition (g = -0.44; p = .03) with androgen-deprivation therapy and new-generation hormone therapy. All other effect sizes were small (from g = -0.02 to g = 0.18), and none of them indicated a significant decline in objective cognition. Significant heterogeneity was observed in all domains of objective cognition. CONCLUSIONS: This synthesis presents the first meta-analytic evidence of the negative impact of androgen-deprivation therapy and new-generation hormone therapy on subjective cognition. In contrast, there was no conclusive evidence of a decline in objective cognition. The high heterogeneity underscores the need for homogeneous cognitive research on prostate cancer. PLAIN LANGUAGE SUMMARY: There is no consensus on the cognitive impairment induced by hormone therapy for prostate cancer, despite the implications for patients' care and daily life. This synthesis of published studies demonstrated an increase in perceived cognitive difficulties but did not prove a decline in cognitive performance during treatment.

COVID-19 psychological impact in general practitioners: A longitudinal study.

INTRODUCTION: COVID-19 may have negatively impacted the mental health of front-line healthcare workers, including general practitioners (GPs). This study sought to assess the psychological impact (stress, burnout and self-efficacy) of the COVID-19 outbreak in French GPs. METHODS: We carried out a postal-based survey of all GPs who worked in the French region of Normandy (departments of Calvados, Manche and Orne) from the exhaustive database of the Union Régionale des Médecins libéraux (URML Normandie) as of 15th April 2020 (one month after the first French COVID-19 sanitary lockdown). The second survey was conducted four months later. Four validated self-report questionnaires were used at both inclusion and follow-up: Perceived Stress scale (PSS), Impact of Event Scale-revised (IES-R), Maslach Burnout Inventory (MBI) and General Self-Efficacy scale (GSE). Demographic data were also collected. RESULTS: The sample consists of 351 GPs. At the follow-up, 182 answered the questionnaires (response rate: 51.8%). The mean scores of MBI significantly increased during follow-up [Emotional exhaustion (EE) and Personal accomplishment, P<0.01]. Higher burnout symptoms were found at the 4-month follow-up in 64 (35.7%) and 86 (48.0%) participants (43 and 70 participant at baseline), according respectively to EE and depersonalisation scores (P=0.01 and 0.09, respectively). CONCLUSION: This is the first longitudinal study that has shown the psychological impact of COVID-19 in French GPs. Based on validated a self-report questionnaire, burnout symptoms increased during follow-up. It is necessary to continue monitoring psychological difficulties of healthcare workers especially during consecutive waves of COVID-19 outbreak.

Posttraumatic Stress Symptoms in Patients With Cancer During the COVID-19 Pandemic: A One-Year Longitudinal Study.

BACKGROUND: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms. METHODS: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown. PTSS were measured every 3 months from April 2020 using the Impact of Event Scale-Revised. Patients also completed questionnaires on their quality of life, cognitive complaints, insomnia, and COVID-19 lockdown experience. RESULTS: Longitudinal analyses involved 386 patients with at least one PTSS assessment after baseline (median age, 63 years; 76% female). Among them, 21.5% had moderate/severe PTSS during the first lockdown. The rate of patients reporting PTSS decreased at lockdown release (13.6%), increased again at second lockdown (23.2%), and slightly declined from the second release period (22.7%) to the third lockdown (17.5%). Patients were grouped into 3 trajectories of evolution. Most patients had stable low symptoms throughout the period, 6% had high baseline symptoms slowly decreasing over time, and 17.6% had moderate symptoms worsening during the second lockdown. Female sex, feeling socially isolated, worrying about COVID-19 infection, and using psychotropic drugs were associated with PTSS. PTSS were associated with impaired quality of life, sleep, and cognition. CONCLUSIONS: Approximately one-fourth of patients with cancer experienced high and persistent PTSS over the first year of the COVID-19 pandemic and may benefit from psychological support. CLINICALTRIALS: gov identifier: NCT04366154.

Identification of seven psychedelic 2,5-dimethoxy-phenylethyl-amine-based designer drugs via benchtop 1 H nuclear magnetic resonance spectroscopy.

The dissemination of spectral information of new psychoactive substances (NPS) acquired on benchtop nuclear magnetic resonance (NMR) spectrometers is of high importance considering the emerging application of such portable and accessible instruments in forensic analyses. Seven members of the 2C-X series (2C-B, 2C-C, 2C-D, 2C-E, 2C-P, 2C-T2, and 2C-T7) of NPS were analyzed via 60 MHz 1 H benchtop NMR spectroscopy and their molecular structural relations are discussed with respect to the observed proton NMR spectra.

Impact of taxane-based chemotherapy among older women with breast cancer on cognition and quality of life: a longitudinal pooled analysis.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Cognitive assessment in patients treated by immunotherapy: the prospective Cog-Immuno trial.

BACKGROUND: The discovery of the importance of the immune system and its role in oncogenesis led to the development of immunotherapy, a treatment that represents a major advance in oncology management. Due to the recent nature of immunotherapy, little is known about its side effects and their impact on quality of life. To date, there is no published study that accurately assesses the impact of immunotherapy on cognition, mood and/or fatigue in patients treated for cancer, despite potential neurological toxicities. The purpose of this study is to prospectively assess the incidence of cognitive impairment and cognitive complaints among cancer patients naïve for immunotherapy without concomitant anti-cancer treatment. METHODS: The Cog-Immuno trial is a multicentre longitudinal study addressing patients with cancer candidate to receive immunotherapy alone (n = 100). Immunotherapy treatment will include either anti-PD1/PDL1 or anti-CTLA4 monotherapy or combination therapy. Cognitive and quality of life assessment, electrocardiogram (ECG) and biological tests will be performed at baseline, thereafter 3, and 6 months after immunotherapy initiation. The primary endpoint is the proportion of patients treated by immunotherapy who will experience a decline in cognitive performances or in Montreal Cognitive Assessment (MoCA) score within 3 months after inclusion. Secondary endpoints concern: anxiety, depression, fatigue, clinical characteristics, biological data and neurophysiological measures (heart rate variability and hemispheric lateralization). A pre-clinical study will be conducted in cancer bearing mice receiving checkpoint inhibitors (ICI) with the evaluation of cognitive functions and emotional reactivity, collection of blood samples and investigation of neurobiological mechanisms from brain slices. DISCUSSION: Assessing and understanding the incidence and the severity of cognitive impairment and its impact on quality of life in cancer patients treated by immunotherapy is a major issue. The results of this study will provide information on the impact of these treatments on cognitive functions in order to help the physicians in the choice of the treatment. TRIAL REGISTRATION: NCT03599830, registered July 26, 2018. PROTOCOL VERSION: Version 5.1 dated from 2020/10/02.

Psychological impact of the COVID-19 outbreak in community pharmacists: A longitudinal study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has negatively affected the mental health of frontline health care workers, including pharmacists. OBJECTIVES: The aim of this longitudinal study was to assess the psychological impact of the COVID-19 outbreak in French owner community pharmacists. METHODS: We conducted a postal-based survey to assess the psychological difficulties of the COVID-19 outbreak in French owner community pharmacists based on 3 psychologically validated self-report questionnaires: Perceived Stress Scale (PSS), Impact of Event Scale-revised (IES-R), and Maslach Burnout Inventory. The baseline assessment was during the first sanitary lockdown period and the second one 5 months later. RESULTS: The sample consists of 135 owner community pharmacists. At follow-up, 67 answered the questionnaires (response rate: 49.6%). The mean scores of the PSS and IES-R significantly decreased (P = 0.002). Fifteen pharmacists reported significant posttraumatic stress symptoms (23.1%) at baseline and 11 at follow-up (16.4%, P = 0.02). Age and sex were not significantly associated with persistent posttraumatic stress or burnout symptoms. CONCLUSION: This is the first longitudinal study that showed the psychological impact of owner community pharmacists as health care workers dealing with their community's COVID-19 outbreak. Based on validated self-report questionnaires, stress, posttraumatic stress, and burnout symptoms decreased during follow-up. It is necessary to continue monitoring psychological difficulties for health care workers, especially during consecutive waves of the COVID-19 outbreak.

Post-traumatic stress symptomatology and adjustment of medical oncology practice during the COVID-19 pandemic among adult patients with cancer in a day care hospital.

BACKGROUND: The COVID-19 pandemic may induce post-traumatic stress disorder (PTSD) symptoms among patients with cancer, who also face adaptations to their treatment. The authors assessed the occurrence of PTSD symptoms, investigated pandemic-induced adjustments in medical oncology practice in patients with cancer, and explored risk factors for PTSD and the association between PTSD symptoms, insomnia, and quality of life (QoL). METHODS: This prospective French study was conducted in patients with solid/hematologic tumors who were receiving medical treatment in the day care departments of 2 cancer centers during the lockdown. Adjustments to medical oncology practice were collected from medical records. PTSD (measured using the Impact of Event Scale-Revised), insomnia (measured using the Insomnia Severity Index), QoL (measured using the Functional Assessment of Cancer Therapy-General instrument), and cognitive complaints (measured using the Functional Assessment of Cancer Therapy-Cognitive Function instrument) were collected through validated questionnaires. RESULTS: Clinical data and questionnaires were available for 734 and 576 patients, respectively. The median patient age was 64 years, and 69% of patients were women. Twenty-one percent of patients had PTSD. Twenty-seven percent (95% CI, 23%-30%) had an adjustment in their medical oncology program, including adjournments (29%), treatment interruptions (16%), modified treatment plans (27%), or adapted monitoring (27%). Women and patients experiencing an adjustment in oncology practice had a higher odds of PTSD (odds ratio= 2.10 [95% CI, 1.07-4.14] and 1.65 [95% CI, 1.03-2.63]; P < .05). PTSD symptoms were correlated with worse scores for QoL, cognition, and insomnia. CONCLUSIONS: Twenty-one percent of patients with cancer experienced PTSD symptoms associated with poor QoL during the first COVID-19-induced lockdown. Medical oncology practice was adjusted in approximately one-quarter of patients and was associated with the occurrence of PTSD symptoms. Psychosocial support should be offered in cancer centers to promote emotional resilience and avoid PTSD symptoms in patients.

Differentiation of groups of patients with cognitive complaints at breast cancer diagnosis: Results from a sub-study of the French CANTO cohort.

OBJECTIVE: Cognitive complaints are more frequent in women with breast cancer (BC) than in healthy controls and can be present before any treatment. Findings regarding contributive factors remain inconsistent. This study aimed to identify different groups of patients with cognitive complaints at BC diagnosis and to determine whether these different groups were associated with demographic, medical, or psychological characteristics. METHODS: Cognitive complaints were assessed in a subset of 264 women from the French multicenter prospective CANTO cohort, at baseline before any treatment. Clustering analyzes were performed using the six-cognitive dimension Costa's scoring of the FACT-Cog V3. Univariable analyses were used to study how cognitive function (standardized neuropsychological tests, ICCTF), anxiety, depression, fatigue, and quality of life (HADS, FA12, QLQ-C30) were associated with specific cognitive complaints groups. RESULTS: Results included 263 women (54±11 years), newly diagnosed with BC (69% stages I-III). Four distinct groups emerged, ranged from "no complaints" (22.8%), "low complaints" (55.1), "mixed complaints" (14.5%), to "consistent complaints" (7.6%). No significant differences were found in terms of demographic and medical factors between the four groups. However, the groups with higher proportions of patients with complaints were found to have more impairment in executive function, higher scores of anxiety, depressive symptoms, and fatigue, and lower quality of life, than the groups with lower proportions of cognitive complaints. CONCLUSION: Using complete cognitive assessment prior to BC treatment, we identified four distinct cognitive complaints groups with specific characteristics. This work provides valuable clinical basis to further investigations for a better understanding of cognitive complaints and their associates.

Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial.

BACKGROUND: There is no treatment for cancer-related cognitive impairment, an important adverse effect that negatively impacts quality of life (QOL). We conducted a 3-arm randomized controlled trial to evaluate the impact of computer-assisted cognitive rehabilitation (CR) on cognition, QOL, anxiety, and depression among cancer patients treated with chemotherapy. METHODS: Patients who reported cognitive complaints during or after completing chemotherapy were randomly assigned to 1 of 3 12-week CR programs: computer-assisted CR with a neuropsychologist (experimental group A), home cognitive self-exercises (active control group B), or phone follow-up (active control group C). Subjective cognition was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), objective cognition was assessed by neuropsychological tests, QOL was assessed by the FACT-General, and depression and anxiety were assessed by psychological tests. The primary endpoint was the proportion of patients with a 7-point improvement in the FACT-Cog perceived cognitive impairment (PCI) score. RESULTS: Among the 167 enrolled patients (median age, 51 years), group A had the highest proportion of patients with a 7-point PCI improvement (75%), followed by groups B (59%) and C (57%), but the difference was not statistically significant (P = .13). Compared with groups B and C, the mean difference in PCI score was significantly higher in group A (P = .02), with better perceived cognitive abilities (P < .01) and a significant improvement in working memory (P = .03). Group A reported higher QOL related to cognition (FACT-Cog QOL) (P = .01) and improvement in depression symptoms (P = .03). CONCLUSIONS: These results suggest a benefit of a computer-based CR program in the management of cancer-related cognitive impairment and complaints.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

BACKGROUND: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. PATIENTS AND METHODS: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. RESULTS: The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. CONCLUSION: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy.

Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol.

BACKGROUND: Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM. METHODS: The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa. DISCUSSION: Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer. TRIAL REGISTRATION: NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

Correction to: Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol.

CORRECTION: After publication of the original article [1] the authors found that Table 2 had been formatted incorrectly, meaning that some rows in the Table did not display the correct information. An updated version of Table 2 is included with this Correction. The original article has also been updated.

Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol.

BACKGROUND: New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa. METHODS/DESIGN: The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments. DISCUSSION: Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of the treatment. TRIAL REGISTRATION: NCT02907372 , registered: July 26, 2016.

Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.

BACKGROUND: The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC). PATIENTS AND METHODS: The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index. RESULTS: Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05). CONCLUSION: This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. IMPLICATIONS FOR PRACTICE: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.

Cognitive complaints in cancer: The French version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), normative data from a healthy population.

Cancer patients often report cognitive changes after chemotherapy. The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report questionnaire that assesses these changes. The aims of the present study were (1) to establish normative data, and (2) to compare the scores of patients and healthy controls to assess whether or not the questionnaire is able to discriminate between these populations. The normative sample included 213 healthy participants. The patient group included 63 cancer patients treated with chemotherapy, who were compared to a subsample of 63 matched healthy controls. The questionnaire had good internal consistency reliability (Cronbach's alphas = .74-.91). The oldest patients had significantly more cognitive complaints (p < .001). Cognitive complaints were significantly related with Trail Making Test scores (p < .001). Furthermore, the FACT-Cog subscales correlated significantly with anxiety and depression. Patients had more complaints than matched controls on the subscales Perceived Cognitive Impairments (p = .01), Impact on Quality of Life (p = .001) and Perceived Cognitive Abilities (p = .027). The reference values from the healthy population reported here could be used for comparison with the values measured in French-speaking cancer patients. The values provide a benchmark against which clinicians can evaluate the impact of the disease and/or the treatments on cognitive complaints and help to improve quality of life by providing appropriate care.

Digital cognitive stimulation in elderly breast cancer patients: the Cog-Tab-Age feasibility study.

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.

Cognition and Return to Work Status 2 Years After Breast Cancer Diagnosis.

Importance: Return to work after breast cancer (BC) treatment depends on several factors, including treatment-related adverse effects. While cancer-related cognitive impairment is frequently reported by patients with BC, to date, no longitudinal studies have assessed its association with return to work. Objective: To examine whether cognition, assessed using objective and subjective scores, was associated with return to work 2 years after BC diagnosis. Design, Setting, and Participants: In a case series of the French Cancer Toxicities (CANTO) cohort, a study of patients with stage I to III BC investigated cognition from April 2014 to December 2018 (2 years' follow-up). Participants included women aged 58 years or younger at BC diagnosis who were employed or looking for a job. Main Outcomes and Measures: The outcome was return to work assessed 2 years after BC diagnosis. Objective cognitive functioning (tests), cognitive symptoms, anxiety, depression, and fatigue were prospectively assessed at diagnosis (baseline), 1 year after treatment completion, and 2 years after diagnosis. Multivariable logistic regression models were used to explain return to work status at year 2 according to each cognitive measure separately, adjusted for age, occupational class, stage at diagnosis, and chemotherapy. Results: The final sample included 178 women with BC (median age: 48.7 [range, 28-58] years), including 37 (20.8%) who did not return to work at year 2. Patients who returned to work had a higher (ie, professional) occupational class and were less likely to have had a mastectomy (24.1% vs 54.1%; P < .001). Return to work at year 2 was associated with lower overall cognitive impairment (1-point unit of increased odds ratio [1-pt OR], 0.32; 95% CI, 0.13-0.79; P = .01), higher working memory (1-pt OR, 2.06; 95% CI, 1.23-3.59; P = .008), higher processing speed (1-pt OR, 1.97; 95% CI, 1.20-3.36; P = .01) and higher attention performance (1-pt OR, 1.63; 95% CI, 1.04-2.64; P = .04), higher perceived cognitive abilities (1-pt OR, 1.12; 95% CI, 1.03-1.21; P = .007), and lower depression (1-pt OR, 0.83; 95% CI, 0.74-0.93; P = .001) at year 2 assessment. Return to work at year 2 was associated with several measures assessed at baseline and year 1: higher processing speed (1-pt OR, 2.38; 95% CI, 1.37-4.31; P = .003 and 1.95; 95% CI, 1.14-3.50; P = .02), higher executive performance (1-pt OR, 2.61; 95% CI, 1.28-5.75; P = .01, and 2.88; 95% CI, 1.36-6.28; P = .006), and lower physical fatigue (10-pt OR, 0.81; 95% CI, 0.69-0.95; P = .009 and 0.84; 95% CI, 0.71-0.98; P = .02). Conclusions and Relevance: In this case series study of patients with BC, return to work 2 years after diagnosis was associated with higher cognitive speed performance before and after BC treatment. Cognitive difficulties should be assessed before return to work to propose suitable management.

How does subjective social status at school at the age of 15 affect the risk of depressive symptoms at the ages of 18, 21, and 28? A longitudinal study.

BACKGROUND: Young people's mental health is declining. Depression is a public disease which is increasing internationally, and in Denmark an increase is seen especially among young people. Objective social status is known to be associated with mental health and depression, but little is known about the association between adolescent subjective social status at school and depressive symptoms during young adulthood. The aim was to investigate the association between 15-year-old's subjective social status at school and the development of depressive symptoms at age 18, 21 and 28. METHODS: The study is a longitudinal study using questionnaire data from The West Jutland Cohort Study Denmark. The study population consisted of adolescents who at baseline, at age 15 (2004), had answered questions about their subjective social status in school using the MacArthur scale-youth version. Answers were categorised into low, medium, and high subjective social status. Outcome data about depressive symptoms was collected at age 18 (2007), age 21 (2010) and age 28 (2017) using the CES-DC and CES-D scales, dichotomised into few or many depressive symptoms. The associations between subjective social status at school at age 15 and depressive symptoms at ages 18, 21 and 28 were analysed using multiple logistic regression. RESULTS: Statistically significant associations were found between low subjective social status at school at age 15 and the odds of many depressive symptoms at all three age points in young adulthood. When adjusting for co-variates the odds ratio for many depressive symptoms at age 18 was OR 3.34 [1.84;6.08], at age 21 OR 3.31 [1.75;6.26] and at age 28 OR 2.12 [1.13;3.97]. CONCLUSIONS: The subjective social status of 15-year-olds is associated with depressive symptoms at ages 18, 21 and 28, respectively. It seems that subjective social status at age 15 is of greatest importance for the occurrence of depressive symptoms in the short run, and that the impact attenuates over time.