Protocol for the Development and Initial Validation of the COG-IMPACT Tool: A Purpose-Built Unmet Needs Assessment for Cancer-Related Cognitive Impairment.

(1) Background: A significant proportion of cancer survivors report experiencing a cognitive 'fog' that affects their ability to think coherently and quickly, and reason with clarity. This has been referred to as cancer-related cognitive impairment (CRCI). CRCI has extensive impacts on the daily lives of people living with or beyond cancer, including occupational, social, and psychological functioning. Oncology health professionals report feeling under-resourced to effectively assess the needs of an individual with CRCI and then provide optimal care and referral. (2) Methods: The objective of this project is to develop and provide an initial validation of the first purpose-built unmet needs assessment for CRCI: the Unmet Needs Assessment of Cancer-Related Cognitive Impairment Impact (COG-IMPACT). We will use a multiple-stage, co-design, mixed-methods approach to develop and provide an initial validation of the COG-IMPACT. (3) Results: The primary anticipated result of this research is the production of the COG-IMPACT, the first purpose-built unmet needs assessment for CRCI. The assessment could be used by health professionals to understand the unmet needs and facilitate optimal care and referral for cancer survivors, by survivors to elucidate their supportive needs and advocate for their care, and by researchers to examine the correlates of unmet needs relating to CRCI, as well as how best to support people with CRCI.

Cancer-related cognitive impairment as a key contributor to psychopathology in cancer survivors: implications for prevention, treatment and supportive care.

A significant proportion of cancer survivors will experience some form of mental health compromise across domains including mood, anxiety, psychosis, eating disorders, and substance use. This psychopathology within cancer survivors is related to a range of negative outcomes and can also have a substantial negative impact on quality of life. Along with psychopathology, cognitive impairments are also commonly experienced, resulting in deficits in memory, reasoning, decision-making, speed of processing, and concentration, collectively referred to as cancer-related cognitive impairment (CRCI). Within the non-oncology literature, cognitive deficits are consistently demonstrated to be a key transdiagnostic aetiological feature of psychopathology, functionally contributing to the development and perpetuation of symptoms. Whilst there is an acknowledgement of the role mental health concerns might play in the development of and perception of CRCI, there has been limited acknowledgement and research exploring the potential for CRCI to functionally contribute toward the development of transdiagnostic psychopathology in cancer survivors beyond simply psychosocial distress. Given the theoretical and empirical evidence suggesting cognitive deficits to be an aetiological factor in psychopathology, we provide a rationale for the potential for CRCI to be a factor in the development and perpetuation of transdiagnostic psychopathology in cancer survivors. This potential functional association has significant implications for risk identification, prevention, treatment, and supportive cancer care approaches regarding psychopathology in cancer survivorship. We conclude by providing directions for future research in this area.

Neuroimaging based biotypes for precision diagnosis and prognosis in cancer-related cognitive impairment.

Cancer related cognitive impairment (CRCI) is commonly associated with cancer and its treatments, yet the present binary diagnostic approach fails to capture the full spectrum of this syndrome. Cognitive function is highly complex and exists on a continuum that is poorly characterized by dichotomous categories. Advanced statistical methodologies applied to symptom assessments have demonstrated that there are multiple subclasses of CRCI. However, studies suggest that relying on symptom assessments alone may fail to account for significant differences in the neural mechanisms that underlie a specific cognitive phenotype. Treatment plans that address the specific physiologic mechanisms involved in an individual patient's condition is the heart of precision medicine. In this narrative review, we discuss how biotyping, a precision medicine framework being utilized in other mental disorders, could be applied to CRCI. Specifically, we discuss how neuroimaging can be used to determine biotypes of CRCI, which allow for increased precision in prediction and diagnosis of CRCI via biologic mechanistic data. Biotypes may also provide more precise clinical endpoints for intervention trials. Biotyping could be made more feasible with proxy imaging technologies or liquid biomarkers. Large cross-sectional phenotyping studies are needed in addition to evaluation of longitudinal trajectories, and data sharing/pooling is highly feasible with currently available digital infrastructures.

Assessing cancer-related cognitive function in the context of everyday life using ecological mobile cognitive testing: A protocol for a prospective quantitative study.

Objective: Millions of cancer survivors are at risk for cancer-related cognitive impairment (CRCI), yet accurate and accessible assessments of cognitive functioning remain limited. Ecological mobile cognitive testing (EMCT) could offer a solution. This paper presents the protocol for a study that aims to (1) establish the reliability and validity of EMCT to assess CRCI in breast cancer survivors, and (2) prospectively evaluate within-person processes (and interactions) among context, mood, and behavior that explain cognitive variability, everyday functioning, and quality of life of cancer survivors. Methods: Participants will include breast cancer survivors (>21 years old) who are within 5 years of completing chemotherapy treatment. Participants will complete two virtual visits (baseline, follow-up) 2 months apart to assess self-reported cognitive symptoms and cognitive performance, sociodemographic characteristics, clinical history, everyday functioning, and quality of life. Between virtual visits, EMCT will be used to sample cognitive functioning every other day (28 times total). We will use linear mixed-effect regressions and single-level multiple regression models to analyze the data. Results: We anticipate a minimum of 124 breast cancer survivors enrolling and completing data collection. Study results will be published in peer-reviewed scientific journals. Conclusions: Our findings will have broad implications for assessing CRCI in an ecologically valid and person-centered way using EMCT. We aim to provide this protocol to aid researchers who would like to apply this approach to their studies.

Validating the PROMIS cognitive function short form in cancer survivors.

PURPOSE: The Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a  (PROMIS Cog) could provide a shorter, useful alternative to the often used Functional Assessment of Cancer Therapy - Cognition (FACT-Cog) in research and clinical care. This study aimed to determine the convergent validity and internal reliability of the PROMIS Cog in 3 separate samples of breast cancer survivors and to explore clinical cut points. METHODS: Data from three samples of breast cancer survivors were used for this secondary analysis. Convergent validity was determined by evaluating correlation strength among the derived PROMIS Cog and measures of depression, anxiety, stress, fatigue, sleep, loneliness, the FACT-Cog . Clinical cut-points for the PROMIS Cog were determined by plotting the receiver operating characteristic curves. RESULTS: 3 samples of breast cancer survivors (N = 471, N = 132, N = 90) were included. Absolute values of correlations demonstrating convergent validity ranged from 0.21 to 0.82, p's < 0.001, and were comparable to correlations with the full FACT-Cog 18 item perceived cognitive impairments (PCI) scale. ROC curve plots indicated a clinical cut off < 34 for the combined sample. CONCLUSION: The 8-item PROMIS Cog demonstrated good convergent validity and internal reliability in breast cancer survivors, comparable to the 18-item FACT-Cog PCI. The PROMIS Cog 8a is a brief self-report measure that can be easily incorporated into cancer-related cognitive impairment research designs or used in clinical settings.

Clinical, psychosocial, and sociodemographic factors of sexual and gender minority groups with cancer: A systematic review.

PURPOSE: Psychosocial health varies depending on demographic and clinical factors and the social context in which individuals grow and live. Sexual and gender minority (SGM) populations experience health disparities due to systemic factors that privilege cisgender and heterosexual identities. We reviewed the literature on the psychosocial, sociodemographic, and clinical factors in SGM groups with cancer and described the associations among these factors. METHODS: We conducted a systematic review according to Fink's methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in the PubMed, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, and LGBTQ+ Life databases. Quantitative articles published in English or Spanish were included. Grey literature and studies with participants in hospice care were excluded. The quality of the publications was assessed with the Joanna Briggs Institute criticalappraisal tools. RESULTS: The review included 25 publications. In SGM groups, systemic cancer treatment was associated with worse psychosocial outcomes; and older age, employment, and higher income were associated with better psychosocial outcomes. CONCLUSIONS: SGM groups with cancer are different from their heterosexual cisgender peers in sociodemographic, psychosocial, and clinical factors. Clinical and sociodemographic factors are associated with psychosocial outcomes among SGM individuals with cancer.

Cisheteronormativity and its influence on the psychosocial experience of LGBTQ+ people with cancer: A qualitative systematic review.

OBJECTIVE: Cisheteronormativity refers to the relationship of heterosexual and cisgender privilege stemming from patriarchy. Although studies have shown that cisheteronormativity can impact health outcomes for lesbian, gay, bisexual, transgender, queer and other sexual, gender diverse, and gender nonconforming (LGBTQ+) people, the specific impact on cancer care has not been described. We synthesized the qualitative evidence on how cisheteronormativity impacts the psychosocial experience of LGBTQ+ people with cancer. METHODS: We conducted a historic search in the CINAHL, LGBT+ Health, PsycInfo, and PubMed databases. Qualitative studies that described the psychosocial experience of LGBTQ+ people with cancer were included. After appraising the quality of the publications, 11 articles were included. Then, we conducted inductive nominal coding, taxonomic analysis, and thematic synthesis. RESULTS: Two main themes emerged, (1) Cisheteronormativity as a social determinant of health, and (2) Cancer, sexual orientation, and gender: Associations and introjections. The themes comprise four categories and 13 subcategories that describe the impact of cisheteronormativity on the cancer experience of LGBTQ+ people. CONCLUSION: Cisheteronormativity within the healthcare system impacts the psychosocial experience of LGBTQ+ people with cancer. Understanding how these gender biases, norms, and social expectations impact the cancer experience is necessary to transform social norms and promote health equity.

Subjective cancer-related cognitive impairments and salience network connectivity in breast cancer survivors.

PURPOSE: Little is known about the neural basis of subjective cancer-related cognitive changes. The purpose of this study was to explore salience network connectivity in relation to subjective executive and memory dysfunction in breast cancer survivors compared to controls. METHODS: A retrospective cross-sectional analysis of neuroimaging, subjective cognitive, clinical, and demographic data in chemotherapy-treated primary breast cancer survivors compared to frequency matched controls was used. Functional connectivity within salience network hubs (anterior cingulate, bilateral insula) was determined using resting state functional MRI. Mann-Whitney U tests were used to evaluate group differences and Spearman's rho correlations were examined among the behavioral measures and salience network connectivity. RESULTS: We included 65 breast cancer survivors and 71 controls. Survivors demonstrated greater subjective executive dysfunction and memory complaints (p < .001) and lower salience network connectivity (p < .05) than controls. Executive functioning correlated with bilateral insula and left anterior cingulate connectivity (rho > - 0.29, p < .05). Distress did not correlate with salience network connectivity. CONCLUSION: These findings suggest that salience network connectivity may represent a biomarker of subjective cancer-related cognitive changes. IMPLICATIONS FOR CANCER SURVIVORS: Subjective cancer-related cognitive changes are common following treatment and associated with objective changes in brain connectivity.

Identifying Themes for Assessing Cancer-Related Cognitive Impairment: Topic Modeling and Qualitative Content Analysis of Public Online Comments.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is a common and significant adverse effect of cancer and its therapies. However, its definition and assessment remain difficult due to limitations of currently available measurement tools. OBJECTIVE: This study aims to evaluate qualitative themes related to the cognitive effects of cancer to help guide development of assessments that are more specific than what is currently available. METHODS: We applied topic modeling and inductive qualitative content analysis to 145 public online comments related to cognitive effects of cancer. RESULTS: Topic modeling revealed 2 latent topics that we interpreted as representing internal and external factors related to cognitive effects. These findings lead us to hypothesize regarding the potential contribution of locus of control to CRCI. Content analysis suggested several major themes including symptoms, emotional/psychological impacts, coping, "chemobrain" is real, change over time, and function. There was some conceptual overlap between the 2 methods regarding internal and external factors related to patient experiences of cognitive effects. CONCLUSIONS: Our findings indicate that coping mechanisms and locus of control may be important themes to include in assessments of CRCI. Future directions in this field include prospective acquisition of free-text responses to guide development of assessments that are more sensitive and specific to cognitive function in patients with cancer.

Comparing Fatigue, Loneliness, Daytime Sleepiness, and Stress in Younger and Older Breast Cancer Survivors: A Cross-Sectional Analysis.

BACKGROUND: Breast cancer treatment can negatively affect psychosocial outcomes for breast cancer survivors (BCS), but these outcomes present differently for younger and older survivors. OBJECTIVES: The objective of this study was to compare psychosocial outcomes between younger and older BCS and identify predictors of loneliness in younger BCS. METHODS: This cross-sectional descriptive study of 90 BCS evaluated data on sociodemographic and clinical characteristics and self-reported measures of psychosocial outcomes (fatigue, depressive symptoms, anxiety, loneliness, daytime sleepiness, and stress). Participants were dichotomized into two groups by age (aged less than 50 years and aged 50 years or older). Descriptive statistics, bivariate correlations, and multiple regression were also examined. FINDINGS: Younger BCS reported greater fatigue, loneliness, daytime sleepiness, and stress than older BCS. No between-group differences were found in depressive symptoms or anxiety. Having children and less time since chemotherapy completion were significant predictors of less loneliness in younger BCS.

Effects of meditation compared to music listening on biomarkers in breast cancer survivors with cognitive complaints: secondary outcomes of a pilot randomized control trial.

CONTEXT: We previously reported positive behavioral effects of both daily mantra meditation and classical music listening interventions in breast cancer survivors with cancer related cognitive complaints. OBJECTIVE: The objective of this pilot study was to compare the effects of the meditation intervention to a music listening intervention on biomarkers of inflammation and cellular aging (secondary outcomes) in breast cancer survivors. DESIGN: Randomized control trial, baseline data collection (time 1), post intervention data collection (time 2) SETTING: Community-based, Central Texas PARTICIPANTS: 25 breast cancer survivors (BCS) who were 3 months to 6 years post chemotherapy completion and reported cognitive changes. INTERVENTION(S): Kirtan Kriya meditation (KK) or classical music listening (ML), 8 weeks, 12 min a day MAIN OUTCOME: Telomerase activity [TA], c-reactive protein [CRP], soluble IL-2 receptor alpha [sIL-2Rα], soluble IL-4 receptor [sIL-4R], soluble IL-6 receptor [sIL-6R], soluble tumor necrosis factor receptor II [sTNF-RII], VEGF receptor 2 [sVEGF-R2], and VEGF receptor 3 [sVEGF-R3] RESULTS: Repeated measures analysis of variance models were analyzed from time 1 to time 2 by group for each biomarker. A pattern of greater telomerase activity across time in both groups (F (1,15) = 3.98, p = .06, ω2 = 0.04); significant decreases in sIL-4R across time for both groups (F (1,22) = 6.28, p = .02, ω2 = .003); group*time effect was nominally different but not statistically different for sIL-4R (F(1,22) = 3.82, p = .06, ω2 = .001); and a pattern for a group*time effect with ML group showing higher levels of sVEGF-R3 at time 2 (F (1,20) = 2.59, p = .12, ω2 = .009). No significant effects were found for CRP, sIL-2Rα, sIL-6R, sTNF-RII, or sVEGF-R2.

Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function.

Objective: We aimed to characterize local brain network connectivity in long-term breast cancer survivors compared to newly diagnosed patients. Methods: Functional magnetic resonance imaging (fMRI) and subjective cognitive and psychological function data were obtained from a group of 76 newly diagnosed, pre-treatment female patients with breast cancer (mean age 57 ± 7 years) and a separate group of 80, post-treatment, female breast cancer survivors (mean age 58 ± 8; mean time since treatment 44 ± 43 months). The network-based statistic (NBS) was used to compare connectivity of local brain edges between groups. Hubs were defined as nodes with connectivity indices one standard deviation or more above network mean and were further classified as provincial (higher intra-subnetwork connectivity) or connector (higher inter-subnetwork connectivity) using the participation coefficient. We determined the hub status of nodes encompassing significantly different edges and correlated the centralities of edges with behavioral measures. Results: The post-treatment group demonstrated significantly lower subjective cognitive function (W = 3,856, p = 0.004) but there were no group differences in psychological distress (W = 2,866, p = 0.627). NBS indicated significantly altered connectivity (p < 0.042, corrected) in the post-treatment group compared to the pre-treatment group largely in temporal, frontal-temporal and temporal-parietal areas. The majority of the regions projecting these connections (78%) met criteria for hub status and significantly less of these hubs were connectors in the post-treatment group (z = 1.85, p = 0.031). Subjective cognitive function and psychological distress were correlated with largely non-overlapping edges in the post-treatment group (p < 0.05). Conclusion: Widespread functional network alterations are evident in long-term survivors of breast cancer compared to newly diagnosed patients. We also demonstrated that there are both overlapping and unique brain network signatures for subjective cognitive function vs. psychological distress.

Sustained effects of mantra meditation compared to music listening on neurocognitive outcomes of breast cancer survivors: A brief report of a randomized control trial.

OBJECTIVE: Cancer-related cognitive impairment is common following the end of adjuvant treatment and there are limited treatment options for it. We compared the sustained cognitive (primary) and psychological (secondary) effects of mantra meditation to classical music listening 8 weeks after interventions ended (Time 3) compared to baseline (Time 1). METHODS: A two-group parallel random assignment experimental design was used in a community setting. Thirty one breast cancer survivors (ages 21 to 75, received chemotherapy, and reported cognitive complaints) were randomly assigned to practice mantra meditation (n = 16) or listen to classical music (n = 15) 12 min a day for 8 weeks. No blinding was used. Repeated measures analysis of variance models were used to compare Time 1 and Time 3 data for the 26 survivors (13 per group) who completed the interventions and Time 3 data collection. RESULTS: Verbal fluency (p < .001, ηp2 = 0.58), attention (p = .002, ηp2 = 0.33), immediate memory recall (p < .001, ηp2 = 0.38), perceived cognitive impairment (p < .001, ηp2 = 0.39), and quality of life (p = .001, ηp2 = 0.35) improved significantly across time for both groups. The two conditions did not differ significantly in changes across time. There were no adverse effects. CONCLUSION: Daily mantra meditation or classical music listening may be beneficial for cognitive outcomes and quality of life of breast cancer survivors with cancer-related cognitive impairment. The cognitive benefits appear to be sustained beyond the initial intervention period. Clinical Trials Registration number: NCT03696056, recruitment status completed. The study details can be accessed at: https://clinicaltrials.gov/ct2/show/NCT03696056 KEY MESSAGE: There are limited treatment options for managing cancer-related cognitive impairments. Daily mantra meditation or classical music listening for 12 min a day may improve cognitive outcomes and quality of life for cancer survivors, with no negative side effects.

Neurocognitive Impairment After Hematopoietic Stem Cell Transplant for Hematologic Malignancies: Phenotype and Mechanisms.

Hematopoietic stem cell transplant (HSCT) plays a central role in the treatment of hematologic cancers. With the increasing survival of patients after HSCT, survivorship issues experienced by this population have become an important outcome. Cognitive impairment is an established sequela of HSCT, with studies to date establishing its presence, associated risk factors, and clinical phenotype. There are multiple potential contributors to cognitive impairment after HSCT. Efforts are ongoing to further characterize its clinical phenotype, associated biomarkers, and biologic underpinnings. A fundamental knowledge of post-HSCT cognitive impairment is of value for all clinicians who interface with this population, and further academic efforts are needed to more fully understand the impact of this cancer treatment on brain health. IMPLICATIONS FOR PRACTICE: As survival outcomes after hematopoietic stem cell transplant (HSCT) improve, an awareness of the post-treatment challenges faced by this population has become central to its care. HSCT can have a sustained and broad impact on brain health, causing cognitive dysfunction, fatigue, disturbed mood, and sleep. In affected patients, autonomy, return to work, relationships, and quality of life may all be affected. A fundamental fluency in this area is important for clinicians interfacing with HSCT survivors, facilitating the identification and management of cognitive dysfunction and concurrent symptom clusters, and stimulating interest in these sequelae as areas for future clinical research.

Measuring Self-Reported Cancer-Related Cognitive Impairment: Recommendations From the Cancer Neuroscience Initiative Working Group.

Cancer and its treatments are associated with increased risk for cancer-related cognitive impairment (CRCI). Methods and measures used to study and assess self-reported CRCI (sr-CRCI), however, remain diverse, resulting in heterogeneity across studies. The Patient-Reported Outcomes Working Group has been formed to promote homogeneity in the methods used to study sr-CRCI. In this report, using a psychometric taxonomy, we inventory and appraise instruments used in research to measure sr-CRCI, and we consider advances in patient-reported outcome methodology. Given its psychometric properties, we recommend the Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a for measurement of sr-CRCI in cancer patients and survivors, at a minimum, to increase scientific rigor and progress in addressing CRCI.

A randomized control trial of meditation compared to music listening to improve cognitive function for breast cancer survivors: Feasibility and acceptability.

BACKGROUND: and Purpose: Many breast cancer survivors (BCS) experience persistent cognitive and psychological changes associated with their cancer and/or treatment and that have limited treatment options. Therefore, the purpose of this study was to explore the feasibility and effects of a Kirtan Kriya meditation (KK) intervention on cognitive and psychological symptoms compared to an attention control condition, classical music listening (ML), in BCS. MATERIALS AND METHODS: A randomized control trial design was used. Participants completed eight-week interventions. Cognitive function and psychological symptoms were measured at baseline and post-intervention. Mixed analysis of variance models were examined for all cognitive and psychological outcomes. RESULTS: 27 BCS completed the study. Intervention adherence was 88%. Both groups improved in perceived cognitive impairments, cognition related quality of life, verbal memory, and verbal fluency (p's < 0.01). There were no significant group by time effects for cognitive and psychological outcomes, except stress. The ML group reported lower stress at time 2 (p < 0.05). CONCLUSION: KK and ML are feasible, acceptable, and cost-effective interventions that may be beneficial for survivors' cognition and psychological symptoms. Both interventions were easy to learn, low cost, and required just 12 min/day. Meditation or music listening could offer providers evidence-based suggestions to BCS experiencing cognitive symptoms. CLINICAL TRIALS REGISTRATION NUMBER: NCT03696056.

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects.

Identifying cytokine predictors of cognitive functioning in breast cancer survivors up to 10 years post chemotherapy using machine learning.

INTRODUCTION: The purpose of this study is to explore 13 cytokine predictors of chemotherapy-related cognitive impairment (CRCI) in breast cancer survivors (BCS) 6 months to 10 years after chemotherapy completion using a multivariate, non-parametric approach. METHODS: Cross sectional data collection included completion of a survey, cognitive testing, and non-fasting blood from 66 participants. Data were analyzed using random forest regression to identify the most significant predictors for each of the cognitive test scores. RESULTS: A different cytokine profile predicted each cognitive test. Adjusted R2 for each model ranged from 0.71-0.77 (p's < 9.50-10). The relationships between all the cytokine predictors and cognitive test scores were non-linear. CONCLUSIONS: Our findings are unique to the field of CRCI and suggest non-linear cytokine specificity to neural networks underlying cognitive functions assessed in this study.

Relationships between self-reported sleep quality components and cognitive functioning in breast cancer survivors up to 10 years following chemotherapy.

OBJECTIVE: Links have been made between aspects of sleep quality and cognitive function in breast cancer survivors (BCS), but findings are heterogeneous. The objective of this study is to examine relationships between specific sleep quality components (latency, duration, efficiency, daytime sleepiness, sleep disturbance, use of sleep aids) and cognitive impairment (performance and perceived), and determine which sleep quality components are the most significant contributors to cognitive impairments in BCS 6 months to 10 years post chemotherapy. METHODS: Women 21 to 65 years old with a history of non-metastatic breast cancer following chemotherapy completion were recruited. Data collection included surveys to evaluate sleep quality and perceived cognitive impairments, and neuropsychological testing to evaluate verbal fluency and memory. Descriptive statistics, bivariate correlations, and hierarchical multiple regression were calculated. RESULTS: Ninety women (mean age 49) completed data collection. Moderate significant correlations were found between daytime dysfunction, sleep efficiency, sleep latency, and sleep disturbance and perceived cognitive impairment (Rs = -0.37 to -0.49, Ps < .00049), but not objective cognitive performance of verbal fluency, memory, or attention. After accounting for individual and clinical characteristics, the strongest predictors of perceived cognitive impairments were daytime dysfunction, sleep efficiency, and sleep disturbance. CONCLUSIONS: Findings support links between sleep quality and perceived cognitive impairments in BCS and suggest specific components of sleep quality (daytime dysfunction, sleep efficiency, and sleep disturbance) are associated with perceived cognitive functioning in this population. Findings can assist clinicians in guiding survivors to manage sleep and cognitive problems and aid in the design of interventional research.

Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

INTRODUCTION: Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. METHODS: Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. RESULTS: Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p = .005). CONCLUSIONS: Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.