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PurposeTo examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC).Patients and methodsSixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year).ResultsWBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood.ConclusionObjective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

PURPOSE:Robust circadian rhythms are increasingly recognized as essential to good health. Adult cancer patients with dysregulated circadian activity rhythms (CAR) experience greater fatigue, lower responsiveness to chemotherapy, and shorter time to relapse. There is scant research describing circadian rhythms and associated outcomes in children with cancer. As part of a larger study examining whether a cognitive-behavioral intervention could preserve sleep in children and adolescents with central nervous system cancers hospitalized for high-dose chemotherapy (HDCT), this study aimed to compare CAR of these children to published values and to investigate the relationship between CAR and fatigue. METHODS:Participants aged 4-19 years wore an actigraph throughout their hospitalization (5 days). From activity counts recorded by actigraphy, six CAR variables were calculated: amplitude, 24-h autocorrelation (r24), dichotomy index (I < O), interdaily stability (IS), intradaily variability (IV), and acrophase. Parent-reported child fatigue and child/adolescent self-reported fatigue measures were collected daily. RESULTS:Thirty-three participants were included. Three CAR variables (amplitude, r24, and I < O) showed dysregulation compared to published values. Older age was significantly associated with later acrophase and greater dysregulation of all other CAR variables. Controlling for age, more dysregulated amplitude (p = 0.001), r24 (p = 0.003), IS (p = 0.017), and IV (p = 0.001) were associated with higher parent-reported fatigue; more dysregulated IV (p = 0.003) was associated with higher child-reported fatigue. CONCLUSIONS:Participants demonstrated dysregulated CAR during hospitalization for HDCT. Greater dysregulation was associated with greater fatigue. Research on circadian dysregulation and its relationship to health-related outcomes in children with cancer, and interventions to support circadian rhythmicity, is urgently needed.

ObjectivesTo determine whether a sleep intervention compared with standard of care (SOC) was successful in preserving nighttime sleep in children with central nervous system cancers hospitalized for high-dose chemotherapy (HDCT) and autologous stem cell rescue, and to explore associations between sleep and fatigue during treatment.MethodsAn unblinded, randomized, controlled, multicomponent intervention (NCT00666614) including evidence-based cognitive and behavioral strategies to improve sleep was implemented in 33 children (age 4-12 years) and adolescents (age 13-19 years) during hospitalization. Children wore an actigraph to measure sleep and wake, and reported fatigue scores daily. Parents concurrently kept a sleep diary and reported fatigue scores for their children.ResultsThe mean age was 9.5 ± 3.9 years, 81.8% were white, and 60.6% were male. Sleep in all children was seriously disturbed throughout the study. Children in the intervention group maintained their longest nighttime sleep across the study, while it declined in children receiving SOC (P = 0.009 for interaction). There were few other differences in sleep between groups. Controlling for age and baseline fatigue, higher nighttime activity score, and lower percent sleep were significantly associated with higher next-day adolescent-reported fatigue (P < 0.05); longest sleep was significantly positively associated with next-day child-reported fatigue (P = 0.018).ConclusionIn this sample of children undergoing HDCT, a multicomponent sleep intervention modestly preserved nighttime sleep duration, although overall sleep was poor in both groups. Sleep is an integral component of health, and may influence outcomes of children receiving HDCT. Further investigation into methods of preserving sleep in children undergoing intensive cancer therapy is warranted.

ObjectiveBreast cancer patients frequently complain of cognitive dysfunction during chemotherapy. Patients also report experiencing a cluster of sleep problems, fatigue, and depressive symptoms during chemotherapy. We aimed to understand the complex dynamic interrelationships of depression, fatigue, and sleep to ultimately elucidate their role in cognitive performance and quality of life amongst breast cancer survivors undergoing chemotherapy treatment.MethodsOur study sample comprised 74 newly diagnosed stage I to III breast cancer patients scheduled to receive chemotherapy. An objective neuropsychological test battery and self-reported fatigue, mood, sleep quality, and quality of life were collected at 3 time points: before the start of chemotherapy (baseline: BL), at the end of cycle 4 chemotherapy (C4), and 1 year after the start of chemotherapy (Y1). We applied novel Bayesian network methods to investigate the role of sleep/fatigue/mood on cognition and quality of life prior to, during, and after chemotherapy.ResultsThe fitted network exhibited strong direct and indirect links between symptoms, cognitive performance, and quality of life. The only symptom directly linked to cognitive performance was C4 sleep quality; at C4, fatigue was directly linked to sleep and thus indirectly influenced cognitive performance. Mood strongly influenced concurrent quality of life at C4 and Y1. Regression estimates indicated that worse sleep quality, fatigue, and mood were negatively associated with cognitive performance or quality of life.ConclusionsThe Bayesian network identified local structure (eg, fatigue-mood-QoL or sleep-cognition) and possible intervention targets (eg, a sleep intervention to reduce cognitive complaints during chemotherapy).

STUDY OBJECTIVES:Sleep disturbances are commonly reported by cancer survivors. Systematic light exposure using bright light has been used to improve sleep in other populations. In this secondary data analysis, the effect of morning administration of bright light on sleep and sleep quality was examined in a mixed group of fatigued cancer survivors. METHODS:Forty-four cancer survivors screened for cancer-related fatigue were randomized to either a bright white light or a comparison dim red light condition. Participants were instructed to use a light box every morning for 30 minutes for 4 weeks. Wrist actigraphy and the Pittsburgh Sleep Quality Index were administered at 4 time points: prior to light treatment (baseline), 2 weeks into the intervention, during the last week of the intervention, and 3 weeks postintervention. Thirty-seven participants completed the end-of-intervention assessment. RESULTS:Repeated-measures linear mixed models indicated a statistically significant time × treatment group interaction effect with sleep efficiency improving more in the bright light condition over time compared with the dim light condition (F3,42 = 5.55; P = .003) with a large effect size (partial η2 = 0.28). By the end of the intervention and 3 weeks postintervention, mean sleep efficiency in the bright light group was in the normal range. Medium to large effect sizes were also seen in sleep quality, total sleep time, and wake after sleep onset for participants favoring the bright light condition. CONCLUSIONS:The results suggest that systematic bright light exposure in the morning may have beneficial effects on sleep in fatigued cancer survivors. Larger scale efficacy trials are warranted. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov, Title: Treating Cancer-Related Fatigue Through Systematic Light Exposure, Identifier: NCT01873794, URL: https://clinicaltrials.gov/ct2/show/NCT01873794.

ObjectiveObstructive sleep apnea (OSA) is very common in Parkinson's disease (PD). OSA is known to affect patients' cognition. The present study assessed whether PD patients with OSA (PD + OSA) score lower on cognitive measures than those without OSA (PD - OSA). In addition, this study evaluated whether treating the OSA with continuous positive airway pressure (CPAP) in PD + OSA patients results in an improved cognitive functioning.MethodsEighty-six patients with PD underwent an overnight polysomnography screen for OSA and were administered the Mini-Mental Status Exam (MMSE) and the Montreal Cognitive Assessment (MoCA). This resulted in 38 patients with PD + OSA who were randomly assigned to receive either therapeutic CPAP for 6 weeks (n = 19) or placebo CPAP for three weeks followed by therapeutic CPAP for three weeks (n = 19). Intervention participants completed a neurocognitive battery at baseline and 3- and 6-week time-points.ResultsPatients with PD + OSA scored significantly lower than PD - OSA on the MMSE and MoCA after controlling for age, education, and PD severity. OSA was a significant predictor of cognition (MMSE p

BackgroundTobacco smoking and related health problems are still major public health concerns in the United States despite the declining smoking prevalence.ObjectivesThis study explored differences in smoking prevalence between urban and rural areas potentially relevant to tobacco control efforts in California.MethodsPublic use adult smoking data from the California Health Interview Survey (CHIS) between 2001 and 2011-2012 were analyzed. A total of 282 931 adults were surveyed across the six CHIS cycles. A ZIP code-based geographic classification (Urban, Second-City, Suburban, and Town/Rural) was used to examine the association between smoking prevalence and area of residency.ResultsThe overall smoking prevalence in California decreased from 17.0% in 2001 to 13.8% in 2011-2012. Within each CHIS cycle, the Town/Rural areas had the highest smoking prevalence, followed by Urban and Second-City areas, and Suburban areas had the lowest. Pooled data from all CHIS cycles showed a similar pattern, with rates in Urban, Second-City, Suburban and Town/Rural areas being 15.2%, 15.2%, 13.1% and 17.3%, respectively. Weighted multivariate logistic regression analysis indicated significantly higher odds of smoking in Urban, Second-City and Town/Rural areas compared to Suburban areas (all adjusted odds ratios > 1.10), although this trend varied by race/ethnicity, being present in non-Hispanic Whites and not present in Hispanics.ConclusionsTown/Rural and Urban populations of California are consistently at higher risk of smoking than Suburban populations. These results indicate a need for population-specific tobacco control approaches that address the lifestyle, behavior, and education of disparate populations within the same state or region.

PurposeSleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory.MethodsSixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year).ResultsCompared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values

ObjectiveRapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson's disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD.MethodsA total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD.ResultsAmong the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p=0.01). The RBD group reported more NMS of depression (p=0.012), fatigue (p=0.036), overall sleep (p=0.018), and overall NMS (p=0.002).ConclusionIn PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.

Study objectivesObstructive sleep apnea (OSA), common in Parkinson disease (PD), contributes to sleep disturbances and daytime sleepiness. We assessed the effect of continuous positive airway pressure (CPAP) on OSA, sleep, and daytime sleepiness in patients with PD.DesignThis was a randomized placebo-controlled, crossover design. Patients with PD and OSA were randomized into 6 w of therapeutic treatment or 3 w of placebo followed by 3 w of therapeutic treatment. Patients were evaluated by polysomnography (PSG) and multiple sleep latency test (MSLT) pretreatment (baseline), after 3 w, and after 6 w of CPAP treatment. Analyses included mixed models, paired analysis, and within-group analyses comparing 3 w to 6 w of treatment.SettingSleep laboratory.ParticipantsThirty-eight patients with PD (mean age = 67.2 ± 9.2 y; 12 females).InterventionContinuous positive airway pressure.MeasurementsPSG OUTCOME MEASURES: sleep efficiency, %sleep stages (N1, N2, N3, R), arousal index, apnea-hypopnea index (AHI), and % time oxygen saturation < 90% (%time SaO2 < 90%). MSLT outcome measures: mean sleep-onset latency (MSL).ResultsThere were significant group-by-time interactions for AHI (P < 0.001), % time SaO2 < 90% (P = 0.02), %N2 (P = 0.015) and %N3 (P = 0.014). Subjects receiving therapeutic CPAP showed significant decrease in AHI, %time SaO2 < 90%, %N2, and significant increase in %N3 indicating effectiveness of CPAP in the treatment of OSA, improvement in nighttime oxygenation, and in deepening sleep. The paired sample analyses revealed that 3 w of therapeutic treatment resulted in significant decreases in arousal index (t = 3.4, P = 0.002). All improvements after 3 w were maintained at 6 w. Finally, 3 w of therapeutic CPAP also resulted in overall decreases in daytime sleepiness (P = 0.011).ConclusionsTherapeutic continuous positive airway pressure versus placebo was effective in reducing apnea events, improving oxygen saturation, and deepening sleep in patients with Parkinson disease and obstructive sleep apnea. Additionally, arousal index was reduced and effects were maintained at 6 weeks. Finally, 3 weeks of continuous positive airway pressure treatment resulted in reduced daytime sleepiness measured by multiple sleep latency test. These results emphasize the importance of identifying and treating obstructive sleep apnea in patients with Parkinson disease.

Study objectivesTo evaluate the impact of sleep disorders on non-motor symptoms in patients with Parkinson disease (PD).DesignThis was a cross-sectional study. Patients with PD were evaluated for obstructive sleep apnea (OSA), restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and REM sleep behavior disorder (RBD). Cognition was assessed with the Montreal Cognitive Assessment and patients completed self-reported questionnaires assessing non-motor symptoms including depressive symptoms, fatigue, sleep complaints, daytime sleepiness, and quality of life.SettingSleep laboratory.Participants86 patients with PD (mean age = 67.4 ± 8.8 years; range: 47-89; 29 women).InterventionsN/A.Measurements and resultsHaving sleep disorders was a predictor of overall non-motor symptoms in PD (R(2) = 0.33, p < 0.001) while controlling for age, PD severity, and dopaminergic therapy. These analyses revealed that RBD (p = 0.006) and RLS (p = 0.014) were significant predictors of increased non-motor symptoms, but OSA was not. More specifically, having a sleep disorder significantly predicted sleep complaints (ΔR(2) = 0.13, p = 0.006), depressive symptoms (ΔR(2) = 0.01, p = 0.03), fatigue (ΔR(2) = 0.12, p = 0.007), poor quality of life (ΔR(2) = 0.13, p = 0.002), and cognitive decline (ΔR(2) = 0.09, p = 0.036). Additionally, increasing number of sleep disorders (0, 1, or ≥ 2 sleep disorders) was a significant contributor to non-motor symptom impairment (R(2) = 0.28, p < 0.001).ConclusionIn this study of PD patients, presence of comorbid sleep disorders predicted more non-motor symptoms including increased sleep complaints, more depressive symptoms, lower quality of life, poorer cognition, and more fatigue. RBD and RLS were factors of overall increased non-motor symptoms, but OSA was not.

ObjectivesTo assess the usefulness of actigraphy for assessment of nighttime sleep measures in patients with Parkinson's disease (PD).DesignParticipants underwent overnight sleep assessment simultaneously by polysomnography (PSG) and actigraphy.SettingOvernight sleep study in academic sleep research laboratory.ParticipantsSixty-one patients (mean age 67.74 ± 8.88 y) with mild to moderate PD.MeasurementsSleep measures including total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) were calculated independently from data derived from PSG and from actigraphy. Different actigraphy scoring settings were compared.ResultsNo single tested actigraphy scoring setting was optimal for all sleep measures. A customized setting of an activity threshold of 10, with five consecutive immobile minutes for sleep onset, yielded the combination of mean TST, SE, and WASO values that best approximated mean values determined by PSG with differences of 6.05 ± 85.67 min for TST, 1.1 ± 0.641% for SE, and 4.35 ± 59.56 min for WASO. There were significant but moderate correlations between actigraphy and PSG measurements (rs = 0.496, P < 0.001 for TST, rs = 0.384, P = 0.002 for SE, and rs = 0.400, P = 0.001 for WASO) using these settings. Greater disease stage was associated with greater differences between TST (R(2) = 0.099, beta = 0.315, P = 0.018), SE (R(2) = 0.107, beta = 0.327, P = 0.014), and WASO (R(2) = 0.094, beta = 0.307, P = 0.021) values derived by actigraphy and PSG explaining some of the variability. Using a setting of 10 immobile min for sleep onset yielded a mean SOL that was within 1 min of that estimated by PSG. However SOL values determined by actigraphy and PSG were not significantly correlated at any tested setting.ConclusionsOur results suggest that actigraphy may be useful for measurement of mean TST, SE, and WASO values in groups of patients with mild to moderate Parkinson's disease. However, there is a significant degree of variability in accuracy among individual patients. The importance of determining optimal scoring parameters for each population studied is underscored.

This study examined the longitudinal relation between health-related quality of life (HR-QOL) and subjective and objective sleep quality in 166 women with newly diagnosed Stage-1 through Stage-3 breast cancer, who were scheduled to receive ≥ 4 cycles of adjuvant/neoadjuvant chemotherapy. HR-QOL was assessed with the Medical Outcomes Study 36-item Short Form, Physical Component Scale (PCS), and Mental Component Scale (MCS) scores; subjective sleep was assessed with the Pittsburgh Sleep Quality Index; and objective sleep was measured with actigraphy. Data were collected before starting chemotherapy and during the last week of Cycle 4 of chemotherapy. Patients reported poor HR-QOL and poor sleep quality before and during chemotherapy. Short sleep time and long naps were recorded at both time points. The MCS score was related to reports of poor sleep, but not to recorded sleep; worse PCS scores were associated with reports of poor sleep and less recorded naptime, suggesting sleep plays an important role in cancer patients' HR-QOL.

Goals of workThe goal of this study was to examine the relationship between menopausal symptoms, sleep quality, and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer.Patients and methodsData on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12 weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses, participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre-Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri-Peri), and post-menopausal before and after chemotherapy (Post-Post).Main resultsResults suggested that women within the Pre-Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre-Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri-Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep.ConclusionsContrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings.

IntroductionObstructive sleep apnea (OSA) is common among patients with Alzheimer's disease (AD). Untreated OSA exacerbates the cognitive and functional deficits. Continuous positive airway pressure (CPAP) has recently been shown to have beneficial effects on cognition in AD. Little attention has focused on the long-term benefits of CPAP in these patients.MethodsThis was an exploratory study of sustained CPAP use (mean use = 13.3 months, SD = 5.2) among a subset of participants from an initial 6-week randomized clinical trial (RCT) of CPAP in patients with mild to moderate AD. Follow-up included 5 patients who continued CPAP (CPAP+) after completion of the RCT and 5 patients who discontinued CPAP (CPAP-), matched by time of completion of the initial study. A neuropsychological test battery and sleep/mood questionnaires were administered and effect sizes were calculated.ResultsEven with a small sample size, sustained CPAP use resulted in moderate-to-large effect sizes. Compared to the CPAP- group, the CPAP+ group showed less cognitive decline with sustained CPAP use, stabilization of depressive symptoms and daytime somnolence, and significant improvement in subjective sleep quality. Caregivers of the CPAP+ group also reported that their own sleep was better when compared to the final RCT visit and that their patients psychopathological behavior was improved.ConclusionThe results of this preliminary study raise the possibility that sustained, long-term CPAP treatment for patients with AD and OSA may result in lasting improvements in sleep and mood as well as a slowing of cognitive deterioration. Prospective randomized controlled research trials evaluating these hypotheses are needed.