Mediation of Psychological Capital in Youth Experiencing Homelessness.

BACKGROUND: Youth who experience homelessness engage in behaviors that place them at high risk for disease and injury. Despite their health risk behaviors, these youth display psychological capital, positive attributes of hope, efficacy, resilience, and optimism that motivate them to engage in health-promoting behaviors such as safer sex. However, this array of positive psychological attributes has not been studied in this vulnerable population. OBJECTIVES: The specific aim of this analysis was to determine whether factors of psychological capital mediated the relationship between background risk factors (e.g., race/ethnicity, educational attainment, reason for being homeless, sexual abuse history, and HIV status) and outcomes of condom intention, safer sex behaviors, and life satisfaction among youth who participated in a longitudinal intervention study. METHODS: Using a Solomon four-group design, 602 youth were recruited from drop-in centers in two large cities (Columbus, Ohio, and Austin, Texas) to participate in a brief intervention that included outcomes of enhanced communication skills, goal setting, safer sex behaviors, drug refusal skills, and life satisfaction. Using an autoregressive, cross-lagged, longitudinal mediation model, we tested the direct and indirect effects of background factors, psychological capital, and intervention outcomes. Models were tested for the intervention group alone and the total sample. RESULTS: There were no significant direct or indirect effects of background factors on intervention outcomes among the intervention group, and the model fit was poor. There were also no significant mediating paths via factors of psychological capital and poor model fit for the combined group. DISCUSSION: Findings provide important information about intrinsic strengths of youth experiencing homelessness and psychological capital as a significant construct for understanding health behaviors among disadvantaged and underserved youth. The lack of significant mediation effects may have been due, in part, to the lack of a robust measure of psychological capital. Further study with various background factors and outcomes would contribute further to our understanding of how best to support this population.

Symptom Clusters Seen in Adult COVID-19 Recovery Clinic Care Seekers.

BACKGROUND: COVID-19 symptom reports describe varying levels of disease severity with differing periods of recovery and symptom trajectories. Thus, there are a multitude of disease and symptom characteristics clinicians must navigate and interpret to guide care. OBJECTIVE: To find natural groups of patients with similar constellations of post-acute sequelae of COVID-19 (PASC) symptoms. DESIGN: Cohort SETTING: Outpatient COVID-19 recovery clinic with patient referrals from 160 primary care clinics serving 36 counties in Texas. PATIENTS: Adult patients seeking COVID-19 recovery clinic care between November 15, 2020, and July 31, 2021, with laboratory-confirmed mild (not hospitalized), moderate (hospitalized), or severe (hospitalized with critical care) COVID-19. MAIN MEASURES: Demographics, COVID illness onset, and duration of persistent PASC symptoms via semi-structured medical assessments. KEY RESULTS: Four hundred forty-one patients (mean age 51.5 years; 295 [66.9%] women; 99 [22%] Hispanic, and 170 [38.5%] non-White, racial minority) met inclusion criteria. Using a k-medoids algorithm, we found that PASC symptoms cluster into two distinct groups: neuropsychiatric (N = 186) (e.g., subjective cognitive dysfunction) and pulmonary (N = 255) (e.g., dyspnea, cough). The neuropsychiatric cluster had significantly higher incidences of otolaryngologic (X2 = 14.3, p < 0.001), gastrointestinal (X2 = 6.90, p = 0.009), neurologic (X2 = 441, p < 0.001), and psychiatric sequelae (X2 = 40.6, p < 0.001) with more female (X2 = 5.44, p = 0.020) and younger age (t = 2.39, p = 0.017) patients experiencing longer durations of PASC symptoms before seeking care (t = 2.44, p = 0.015). Patients in the pulmonary cluster were more often hospitalized for COVID-19 (X2 = 3.98, p = 0.046) and had significantly higher comorbidity burden (U = 20800, p = 0.019) and pulmonary sequelae (X2 = 13.2, p < 0.001). CONCLUSIONS: Health services clinic data from a large integrated health system offers insights into the post-COVID symptoms associated with care seeking for sequelae that are not adequately managed by usual care pathways (self-management and primary care clinic visits). These findings can inform machine learning algorithms, primary care management, and selection of patients for earlier COVID-19 recovery referral. TRIAL REGISTRATION: N/A.

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.

Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults.

Answer questions and earn CME/CNE Over the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported-that cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case-study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed.

Health Promotion, Functional Abilities, and Quality of Life Before and During COVID-19 in People With Multiple Sclerosis.

BACKGROUND: Because multiple sclerosis (MS) is an autoimmune disease and many individuals with MS take disease-modifying drugs that suppress immune response, serious concerns have been expressed about the potential effect of COVID-19 on those with this chronic condition. OBJECTIVES: The purpose of this research was to utilize the most recent 5 years of data from an ongoing longitudinal study of health promotion and quality of life (QoL) among people with long-standing MS to investigate changes across time in functional limitations, health promotion, and health-related QoL. METHODS: Participants are mailed an annual survey to complete about their health promotion, depressive symptoms, health status, social support, MS-related functional limitations, and QoL. Differences across time were analyzed with repeated measures of analysis of variances and planned contrasts. RESULTS: In 2021, the 141 participants had a mean age of 69 years and had been diagnosed with MS for 34 years, on average. Most had attended college, were married/partnered women, and reported adequate economic resources. Thirty-seven percent reported they were in poor to fair health. Physical activity and health responsibility scores decreased significantly during 2020-2021 compared with 2017-2019. Significant changes in depressive symptoms, social support, and functional limitation scores followed a different pattern, with the largest changes occurring between 2018 and 2019. QoL and other health promotion scores did not change significantly across time. DISCUSSION: The relatively small changes in health indicators revealed here suggest that older people with long-standing MS may have generally been able to maintain their health promotion, functional abilities, and QoL from before to during the COVID-19 pandemic. However, nurses and other providers should support them to resume their physical activity and regular provider contact as COVID-19 restrictions are eased. The patterns observed here demonstrate the importance of examining changes across an extended period, rather than simply looking at 1 year before and 1 year after a major event, such as COVID-19. These findings can help nurses understand how to help their patients with chronic health conditions maximize their health as they move forward.

Correlates of mental health problems among students in Texas alternative high schools and school-level efforts to address mental health.

Students in alternative high schools (AHSs) are an understudied population who experience disproportionate levels of risk factors that contribute to mental health problems. Using logistic regression, we explored associations between mental health problems and risk and protective factors among students in Texas AHSs (n = 515; mean age 17.1 years; 51% female, 78% youth of color, 64% eligible for free/reduced lunch). Principals (n = 14) and lead health educators (n = 14) reported on school-level efforts to address mental health. Students reported, on average, 1.55 of 4 mental health problems in the past year. Logistic regression indicated that greater number of adverse childhood experiences, lower self-esteem, female gender, and sleep disruption (getting <8 h of sleep per night) were common contributors to symptoms of depression, anxiety, suicidal ideation, and PTSD with models showing medium-to-large effects (AUC: 0.73-0.81). We assessed school-level efforts to address mental health using descriptive statistics. At the school level, most (>50%) principals reported having policies and services to support student mental health, with the exception of having mental health/social services staff represented on school health councils (36%) and having Gay-Straight Alliances (21%). Most lead health educators (86%) reported educating AHS students about mental health, and many (57%) reported receiving professional development in mental health. Future research with a larger number of schools is needed to analyze whether school policies are statistically associated with student-level mental health outcomes. Such multi-level research can inform policies and practices for AHS student mental health.

Headache outcomes of a sleep behavioral intervention in breast cancer survivors: Secondary analysis of a randomized clinical trial.

BACKGROUND: Breast cancer survivors often have persisting headache. In a secondary analysis of the Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) clinical trial (ClinicalTrials.gov identifier NCT02165839), the authors examined the effects of BBT-CI on headache outcomes in patients with breast cancer. METHODS: Patients with breast cancer who were receiving chemotherapy were randomly assigned to receive either the BBT-CI intervention or the Healthy EAting Education Learning for healthy sleep (HEAL) control intervention, and both were delivered over 6 weeks by trained staff. Headache outcomes and heart rate variability (HRV) were measured at baseline, 6 weeks, 6 months, and 12 months. Mixed-effects models were used to examine longitudinal headache outcomes in the groups according to the intention to treat. Principal component analysis and agglomerative hierarchical clustering were conducted to reduce 16 variables for data-driven phenotyping. RESULTS: Patients in the BBT-CI arm (n = 73) exhibited a significant reduction in headache burden over time (P = .02; effect size [Cohen d] = 0.43), whereas the reduction was not significant among those in the HEAL arm (n = 66). The first principal component was positively loaded by headache, sleep, fatigue, and nausea/vomiting and was negatively loaded by cognitive, physical, and emotional functioning. Agglomerative hierarchical clustering revealed 3 natural clusters. Cluster I (n = 58) featured the highest burden of headache, insomnia, and nausea/vomiting; cluster II (n = 50) featured the lowest HRV despite a low burden of headache and insomnia; and cluster III (n = 31) showed an inverse relation between HRV and headache-insomnia, signifying autonomic dysfunction. CONCLUSIONS: BBT-CI is efficacious in reducing headache burden in breast cancer survivors. Patient phenotyping demonstrates a headache type featuring sleep disturbance, nausea/vomiting, and low physical functioning-revealing similarities to migraine. LAY SUMMARY: Breast cancer survivors often have persisting headache symptoms. In patients with cancer, treatment of chronic headache disorders using daily medications may be challenging because of drug interactions with chemotherapy and other cancer therapies as well as patients' reluctance to add more drugs to their medicine list. Headache and sleep disorders are closely related to each other. This study demonstrates that a sleep behavioral therapy reduced headache burden in breast cancer survivors. In addition, the majority of headache sufferers had a headache type with similarities to migraine-featuring sleep disturbance, nausea/vomiting, and low physical functioning.

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.

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.

Biomarkers panels can predict fatigue, depression and pain in persons living with HIV: A pilot study.

BACKGROUND: Persons living with HIV experience high symptom burden that can negatively impact medication adherence, work productivity, and quality of life. Symptoms are highly subjective, which can lead to under- or improper treatment. The purpose of this exploratory study was to examine relationships between circulating biomarkers representative of inflammatory, coagulation, and vascular function pathways and prevalent HIV symptoms. SETTING AND SAMPLE: Adults >18 years who were diagnosed with HIV and spoke English for this cross-sectional study were recruited from community clinics and organizations. METHODS: Symptom burden was measured with the HIV Symptom Index; depression with the Patient Health Questionnaire. Human multiplex kits were used to determine serum concentrations of select biomarkers representing inflammatory, coagulation, and vascular function pathways. The biomarkers were included as features in machine learning models to determine which biomarkers predicted the most prevalent HIV symptoms (fatigue and muscle/joint pain) and the symptom of depression. RESULTS: Participants (N = 32) were representative of the local population of people with HIV, being mostly Black (54.4%) and male (60.6%). Depression was predicted by age, gender, glucose, hemoglobin A1c, and inflammation. Muscle/joint pain was predicted by adiponectin, C-reactive protein, and serum amyloid A (SAA). Fatigue was predicted by adiponectin, SAA, and soluble interleukin-1 receptor type II (sIL-1RII). CONCLUSION: Biomarker clusters can be a tool to monitor symptoms. Adding an objective measure to subjective patient experiences could improve management and monitoring of symptoms. Defining a biomarker cluster for the objective assessment of HIV symptoms warrants further investigation; however, the presence of comorbid conditions needs to be controlled.

Neurocognitive dysfunction in adult cerebellar medulloblastoma.

OBJECTIVE: Impaired neurocognitive function (NCF) is a well-established consequence of pediatric medulloblastoma (MB) and its treatments. However, the frequency and features of neurocognitive dysfunction in adult-onset MB patients are largely unknown. METHODS: Adult patients (≥ 18 years) with MB who had received formal neurocognitive evaluation (N = 27) were identified. Demographic, medical, and treatment histories were extracted from the medical record. Lesion properties on MRI were analyzed and used to evaluate lesion-symptom mapping further. Demographically adjusted z-scores were calculated for each neurocognitive test and used to assess impairment frequency. Regression analyses were conducted to identify clinical and paraclinical factors associated with impaired NCF. RESULTS: Mean age of the patient sample was 33 years (SD = 11) at the time of MB diagnosis. Prior therapy included surgical resection (89%), radiation (70%), and chemotherapy (26%). A significant proportion of patients were impaired on tests of verbal learning and memory (32%), executive function (29%), and naming (18%). Age, education, lesion size, time from surgery, and number of chemotherapy cycles had the greatest contribution to test performance in random-forest regression models. CONCLUSION: This study identifies frequent impairment of NCF in adult patients with MB, particularly in the domains of learning and memory and executive function. Neurocognitive impairment is influenced by patients' demographic, disease, and treatment history. Further study is warranted to characterize the clinical impact of adult MB more fully.

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-ß-cyclodextrin (HPßCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general.

Feasibility and acceptability of brief behavioral therapy for cancer-related insomnia: effects on insomnia and circadian rhythm during chemotherapy: a phase II randomised multicentre controlled trial.

BACKGROUND: This phase II RCT was conducted to determine the feasibility and acceptability of brief behavioral therapy for cancer-related insomnia (BBT-CI) in breast cancer patients undergoing chemotherapy. We also assessed the preliminary effects of BBT-CI on insomnia and circadian rhythm in comparison to a Healthy Eating Education Learning control condition (HEAL). METHODS: Of the 71 participants recruited, 34 were randomised to receive BBT-CI and 37 to receive HEAL. Oncology staff was trained to deliver the intervention in four community clinics affiliated with the NCI. Insomnia was assessed with the Insomnia Severity Index (ISI), and circadian rhythm was assessed using a wrist-worn actiwatch. RESULTS: Community staff interveners delivered 72% of the intervention components, with a recruitment rate of 77% and an adherence rate of 73%, meeting acceptability and feasibility benchmarks. Those randomised to BBT-CI improved their ISI scores by 6.3 points compared to a 2.5-point improvement in those randomised to HEAL (P = 0.041). Actigraphy data indicated that circadian functioning improved in the BBT-CI arm as compared to the HEAL arm at post-intervention (all P-values <0.05). CONCLUSIONS: BBT-CI is an acceptable and feasible intervention that can be delivered directly in the community oncology setting by trained staff. The BBT-CI arm experienced significant improvements in insomnia and circadian rhythm as compared to the control condition.

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.

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

PURPOSE: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. METHODS: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. RESULTS: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). CONCLUSIONS: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. TRIAL REGISTRATION: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Management of side effects during and post-treatment in breast cancer survivors.

Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are commonly experienced symptoms that share psychological and physical manifestations. One or more of these symptoms will affect nearly all patients at some point during their course of treatment or survivorship. These side effects are burdensome and reduce patients' quality of life well beyond their cancer diagnosis and associated care treatments. Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are likely to have multiple etiologies that make it difficult to identify the most effective method to manage them. In this review, we summarized the information on cancer-related fatigue, insomnia, and cancer-related cognitive impairment incidence and prevalence among breast cancer patients and survivors as well as recent research findings on pharmaceutical, psychological, and exercise interventions that have shown effectiveness in the treatment of these side effects. Our review revealed that most current pharmaceutical interventions tend to ameliorate symptoms only temporarily without addressing the underlying causes. Exercise and behavioral interventions are consistently more effective at managing chronic symptoms and possibly address an underlying etiology. Future research is needed to investigate effective interventions that can be delivered directly in clinic to a large portion of patients and survivors.

The effect of IDH1 mutation on the structural connectome in malignant astrocytoma.

Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p < 0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p = 0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p < 0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing.

Task-based neurofeedback training: A novel approach toward training executive functions.

Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100min total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions.

The impact of executive function on response to cognitive behavioral therapy in late-life depression.

OBJECTIVE: Late-life depression (LLD) is a common and debilitating condition among older adults. Cognitive behavioral therapy (CBT) has strong empirical support for the treatment of depression in all ages, including in LLD. In teaching patients to identify, monitor, and challenge negative patterns in their thinking, CBT for LLD relies heavily on cognitive processes and, in particular, executive functioning, such as planning, sequencing, organizing, and selectively inhibiting information. It may be that the effectiveness of CBT lies in its ability to train these cognitive areas. METHODS: Participants with LLD completed a comprehensive neuropsychological battery before enrolling in CBT. The current study examined the relationship between neuropsychological function prior to treatment and response to CBT. RESULTS: When using three baseline measures of executive functioning that quantify set shifting, cognitive flexibility, and response inhibition to predict treatment response, only baseline Wisconsin Card Sort Task performance was associated with a significant drop in depression symptoms after CBT. Specifically, worse performance on the Wisconsin Card Sort Task was associated with better treatment response. CONCLUSIONS: These results suggest that CBT, which teaches cognitive techniques for improving psychiatric symptoms, may be especially beneficial in LLD if relative weaknesses in specific areas of executive functioning are present.

Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls.

Breast cancer (BC) chemotherapy is associated with cognitive changes including persistent deficits in some individuals. We tested the accuracy of default mode network (DMN) resting state functional connectivity patterns in discriminating chemotherapy treated (C+) from non-chemotherapy (C-) treated BC survivors and healthy controls (HC). We also examined the relationship between DMN connectivity patterns and cognitive function. Multivariate pattern analysis was used to classify 30 C+, 27 C-, and 24 HC, which showed significant accuracy for discriminating C+ from C- (91.23%, P < 0.0001) and C+ from HC (90.74%, P < 0.0001). The C- group did not differ significantly from HC (47.06%, P = 0.60). Lower subjective memory function was correlated (P < 0.002) with greater hyperplane distance (distance from the linear decision function that optimally separates the groups). Disrupted DMN connectivity may help explain long-term cognitive difficulties following BC chemotherapy.