Effects of ecgonine methyl ester on cognition in scopolamine-impaired and aged rats.

RATIONALE: Searches for antidotes to cocaine, and for cognition enhancers potentially applicable to Alzheimer's disease, have revealed a novel regulatory site on nicotinic acetylcholine receptors. In the presence of an agonist, inhibitors binding to this site changed the ion channel equilibrium from the open-channel form towards the closed form. Other, related, molecules could bind to the site without changing the equilibrium. These latter compounds were predicted to displace the inhibitors without affecting receptor function per se. These compounds alleviated the inhibition. One of them is ecgonine methyl ester (EME), which is generally described as inactive, but this work suggested a beneficial effect on cognition. OBJECTIVE: This in vivo study tested for cognitive enhancement by EME in scopolamine-impaired, and aged, rats. METHODS: Memory was the primary endpoint, but thigmotaxis became an important secondary endpoint in the light of observations made during the study. Impaired cognition was pharmacologically induced by scopolamine in young rats, and spontaneously present in aged rats. Learning ability before and after administration of EME was tested in Morris water maze protocols. Concentrations of EME in the brain and plasma were analyzed by gas chromatography-mass spectrometry. RESULTS: A single dose of EME reversed scopolamine impairment, indicating involvement of acetylcholine receptors. Longer-term treatment improved cognition in aged rats, with enhanced rates of learning in the absence of an exogenous cognition-impairing compound. Impairment returned with a new challenge; the improvement could be re-established with continued dosing. EME also reversed thigmotaxis seen in aged rats; thigmotaxis is believed to indicate anxiety. The concentrations of EME in the brain proved adequate drug exposure. CONCLUSIONS: Since other investigators have shown cognition impairment caused by cocaine in aged rats, this work shows that cocaine and EME have opposite effects in Morris water maze models. EME might induce cognitive enhancement and relief of anxiety in cocaine-impaired humans, and in other cognitive disorders.

A multicomponent nonpharmacological intervention improves activity rhythms among nursing home residents with disrupted sleep/wake patterns.

BACKGROUND: Sleep and circadian rhythms are disrupted among many nursing home (NH) residents. We examined the impact of a multicomponent nonpharmacological intervention on 24-hour rest/activity rhythms among long-stay NH residents. METHODS: The study was a randomized controlled trial in which, following a 3-day baseline, participants received 5 days of either usual care (control condition) or the active intervention. The intervention combined increased exposure to outdoor bright light, efforts to keep residents out of bed during the day, structured physical activity, institution of a bedtime routine, and efforts to reduce nighttime noise and light in residents' rooms. For 100 residents with baseline and follow-up wrist actigraphy data (mean age = 87 years; 76% women), rest/activity rhythms were modeled to determine the rhythm acrophase (peak time), nadir (trough time), midline estimating statistic of rhythm (MESOR) (midpoint), amplitude (height of peak), slope, and the rest period/active period ratio (alpha). RESULTS: The intervention led to an increase in the duration of the "active" portion of the rhythm, which was primarily accounted for by a shift in the rest/activity rhythm rise to an earlier time. Findings persisted when analyses were adjusted for age, cognitive functioning, medical comorbidities, and behavioral disturbances. CONCLUSIONS: These findings suggest that the intervention may effectively improve the robustness of rest/activity rhythms in NH residents. Further research is needed to examine the impact of similar interventions on other measures of circadian rhythms (e.g., body temperature, melatonin) among NH residents.

Pilot randomized trial of the effect of wireless telemonitoring on compliance and treatment efficacy in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent and serious medical condition characterized by repeated complete or partial obstructions of the upper airway during sleep and is prevalent in 2% to 4% of working middle-aged adults. Nasal continuous positive airway pressure (CPAP) is the gold-standard treatment for OSA. Because compliance rates with CPAP therapy are disappointingly low, effective interventions are needed to improve CPAP compliance among patients diagnosed with OSA. OBJECTIVE: The aim was to determine whether wireless telemonitoring of CPAP compliance and efficacy data, compared to usual clinical care, results in higher CPAP compliance and improved OSA outcomes. METHODS: 45 patients newly diagnosed with OSA were randomized to either telemonitored clinical care or usual clinical care and were followed for their first 2 months of treatment with CPAP therapy. CPAP therapists were not blinded to the participants' treatment group. RESULTS: 20 participants in each group received the designated intervention. Patients randomized to telemonitored clinical care used CPAP an average of 4.1 +/- 1.8 hours per night, while the usual clinical care patients averaged 2.8 +/- 2.2 hours per night (P = .07). Telemonitored patients used CPAP on 78% +/- 22% of the possible nights, while usual care patients used CPAP on 60% +/- 32% of the nights (P = .07). No statistically significant differences between the groups were found on measures of CPAP efficacy, including measures of mask leak and the Apnea-Hypopnea Index. Patients in the telemonitored group rated their likelihood to continue using CPAP significantly higher than the patients in the usual care group. Patients in both groups were highly satisfied with the care they received and rated themselves as "not concerned" that their CPAP data were being wirelessly monitored. CONCLUSIONS: Telemonitoring of CPAP compliance and efficacy data and rapid use of those data by the clinical sleep team to guide the collaborative (ie, patient and provider) management of CPAP treatment is as effective as usual care in improving compliance rates and outcomes in new CPAP users. This study was designed as a pilot-larger, well-powered studies are necessary to fully evaluate the clinical and economic efficacy of telemonitoring for this population.

Continuous positive airway pressure reduces subjective daytime sleepiness in patients with mild to moderate Alzheimer's disease with sleep disordered breathing.

OBJECTIVES: Studies have reported that 33% to 70% of patients with Alzheimer's disease (AD) have sleep-disordered breathing (SDB). Continuous positive airway pressure (CPAP) treatment has been shown to reduce daytime sleepiness and improve health-related quality of life in nondemented older people with SDB. The effect of therapeutic CPAP treatment on daytime sleepiness in patients with mild-moderate AD with SDB was assessed. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Patients' home and the University of California San Diego, General Clinical Research Center, J. Christian Gillin Laboratory of Sleep and Chronobiology. PARTICIPANTS: Thirty-nine community-dwelling elderly patients with mild-moderate probable AD with SDB. INTERVENTION: Patients were randomly assigned to receive 6 weeks of therapeutic CPAP or 3 weeks of sham CPAP followed by 3 weeks of therapeutic CPAP. MEASUREMENTS: Epworth Sleepiness Scale (ESS) was administered at baseline, 3 weeks, and 6 weeks. Changes in daytime sleepiness in subjects who received optimal therapeutic CPAP were compared with changes in the sham CPAP group. RESULTS: Within the therapeutic CPAP group, ESS scores were reduced from 8.89 during baseline to 6.56 after 3 weeks of treatment (P=.04) and to 5.53 after 6 weeks of treatment (P=.004). In the sham CPAP group, there was no significant difference after 3 weeks of sham CPAP but a significant decrease from 7.68 to 6.47 (P=.01) after 3 weeks of therapeutic CPAP. CONCLUSION: These data provide evidence of the effectiveness of CPAP in reducing subjective daytime sleepiness in patients with AD with SDB.

Social-cognitive correlates of CPAP adherence in experienced users.

BACKGROUND AND PURPOSES: Obstructive sleep apnea (OSA) is a condition with serious medical and psychosocial consequences. However, poor adherence with nasal continuous positive airway pressure (CPAP) treatment limits the effectiveness of treatment. Behavior change factors offer one avenue of research to better understand the correlates of CPAP adherence. PATIENTS AND METHODS: Fifty-eight participants who had been diagnosed with OSA and prescribed CPAP treatment agreed to complete questionnaires that assessed sleep apnea symptoms, behavior change factors, and CPAP side effects, and to have their CPAP data downloaded. Behavior change factors from both social cognitive theory (SCT) and the transtheoretical model (TM) were assessed. The primary aim of the study was to examine the relationship between these social-cognitive factors and objectively measured CPAP adherence. RESULTS: Participants had been using CPAP for a mean of 2.1 years. SCT variables (adjusted R(2)=0.115, P=.008) and TM variables (adjusted R(2)=0.157, P<.0001) each accounted for a statistically significant amount of variance in CPAP adherence. CONCLUSIONS: The results suggest that social-cognitive factors may be associated with CPAP adherence in experienced CPAP users. The principal advantage to these theory-driven and empirically validated factors is that they are modifiable and can provide the basis for effective interventions to increase CPAP adherence.

Acetylcholinesterase inhibitors and sleep architecture in patients with Alzheimer's disease.

BACKGROUND AND OBJECTIVE: Studies suggest that some acetylcholinesterase inhibitors (AChEIs) increase rapid eye movement (REM) sleep and nightmares in patients with Alzheimer's disease (AD) but few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs. METHODS: 76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed. RESULTS: AChEI therapy had a significant effect on the percentage of stage 1 (p = 0.01) and stage 2 (p = 0.03) sleep. Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters. CONCLUSION: Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest that sleep architecture may be affected by the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD.

Mortality associated with sleep duration and insomnia.

BACKGROUND: Patients often complain about insufficient sleep or chronic insomnia in the belief that they need 8 hours of sleep. Treatment strategies may be guided by what sleep durations predict optimal survival and whether insomnia might signal mortality risks. METHODS: In 1982, the Cancer Prevention Study II of the American Cancer Society asked participants about their sleep duration and frequency of insomnia. Cox proportional hazards survival models were computed to determine whether sleep duration or frequency of insomnia was associated with excess mortality up to 1988, controlling simultaneously for demographics, habits, health factors, and use of various medications. RESULTS: Participants were more than 1.1 million men and women from 30 to 102 years of age. The best survival was found among those who slept 7 hours per night. Participants who reported sleeping 8 hours or more experienced significantly increased mortality hazard, as did those who slept 6 hours or less. The increased risk exceeded 15% for those reporting more than 8.5 hours sleep or less than 3.5 or 4.5 hours. In contrast, reports of "insomnia" were not associated with excess mortality hazard. As previously described, prescription sleeping pill use was associated with significantly increased mortality after control for reported sleep durations and insomnia. CONCLUSIONS: Patients can be reassured that short sleep and insomnia seem associated with little risk distinct from comorbidities. Slight risks associated with 8 or more hours of sleep and sleeping pill use need further study. Causality is unproven.

The effects of standard anthracycline-based chemotherapy on soluble ICAM-1 and vascular endothelial growth factor levels in breast cancer.

PURPOSE: The circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) are elevated in women with breast cancer and associated with tumor progression and poor prognosis. This study examined the effects of anthracycline-based chemotherapy on plasma sICAM-1 and VEGF, as well as soluble P-selectin, von Willebrand factor, and interleukin-6 levels. EXPERIMENTAL DESIGN: Twenty-six women diagnosed with stage I-IIIA breast cancer (mean age, 48.4 +/- 10.4 years; range, 34-79 years) were studied before (week 1) and at weeks 2 and 3 of cycles 1 and 4 of chemotherapy. RESULTS: The initial effect of chemotherapy was to reduce sICAM-1 levels; compared with pretreatment, sICAM-1 levels were decreased at week 2 of both cycles (P values < 0.01). sICAM-1 levels were elevated, however, at the start of cycle 4 as compared with pretreatment (P < 0.01). Chemotherapy led to an increase in sICAM-1 levels in node-positive but not node-negative patients (P < 0.01). VEGF levels were decreased at week 2 of cycle 4 (P = 0.001) and remained so at week 3. Similar to sICAM-1, VEGF levels were elevated at the start of cycle 4 as compared with pretreatment (P < 0.006). Soluble P-selectin levels decreased during week 2 of cycle 4 (P = 0.026). Neither interleukin-6 or von Willebrand factor were significantly changed in response to chemotherapy. CONCLUSIONS: The findings support prior studies suggesting that sICAM-1 levels derive from sources other than endothelial cells. In addition, whereas the more immediate effect of chemotherapy is to reduce sICAM-1 and VEGF, continued treatment may lead to significant elevations.

Long-term follow-up of periodic limb movements in sleep in older adults.

STUDY OBJECTIVES: The goal of this study was to examine the natural history of periodic limb movements in sleep (PLMS) in older adults. DESIGN: Prospective, longitudinal design. SETTING: San Diego area. PARTICIPANTS: Community-dwelling older adults. INTERVENTIONS: NA MEASUREMENTS AND RESULTS: Subjects participated in follow-up visits every few years. Sleep disorders were assessed at each visit using sleep questionnaires and overnight sleep recordings. Changes in PLMS over time were examined as well as variables that were associated with change. Average PLMS did not change over time, although there was considerable variability within the sample. In women, changes in PLMS were associated with changes in sleep-disordered breathing. This relationship was not found in men. CONCLUSIONS: Although the prevalence of PLMS is high for older adults, the severity of the disorder does not progressively worsen with increasing age.

The effect of race and sleep-disordered breathing on nocturnal BP "dipping": analysis in an older population.

STUDY OBJECTIVES: BP normally drops (or "dips") by approximately 10% at nighttime; however, in a number of illnesses there is an increased amount of "nondipping" of nocturnal BP. This study examined whether nondipping in older African Americans and older white subjects is related to the presence of sleep-disordered breathing (SDB) and hypertension. DESIGN: Prospective study with a convenience sample. SETTING: All data were collected in the subjects' homes. PARTICIPANTS: Seventy self-defined African Americans with complaints of snoring or excessive daytime sleepiness, and 70 age-matched and gender-matched white subjects. MEASUREMENTS AND RESULTS: Sleep was recorded for 2 nights, with 1 night of oximetry. BP was recorded on a separate 24-h period. African Americans had higher dipping ratios than white subjects even after accounting for covariates such as respiratory disturbance index (RDI), oxygen desaturation index (ODI), body mass index, and average 24-h mean arterial pressure (p = 0.025). Higher values of RDI (R(2) = 0.0686, p = 0.021) and ODI (R(2) = 0.042, p < 0.03) were correlated with higher dipping ratios in both African Americans and white subjects. However, there was a three-way interaction such that higher RDIs were correlated primarily with nondipping in African Americans receiving antihypertensive medication (R(2) = 0.0373, p = 0.022). CONCLUSIONS: These results demonstrated that African Americans tend to be "nondippers," while white subjects tended to be "dippers." This nondipping was not a result of weight, gender, or of having SDB. The analyses also confirmed that, in both races, the dipping ratio was greatest in those with SDB and hypertension. The third hypothesis, that RDI would be greatest in the nondipping hypertensive subjects, was true only for the African Americans.

The relationship between congestive heart failure, sleep apnea, and mortality in older men.

STUDY OBJECTIVES: To examine the association of sleep apnea with heart disease. DESIGN: Prospective study. SETTING: Medical wards at the Veterans Affairs San Diego Healthcare System. PATIENTS: Three hundred fifty-three randomly selected inpatient men. MEASUREMENTS AND RESULTS: Sleep was recorded for 2 nights in the hospital. Medical conditions were obtained from hospital medical records. Cox proportional hazards analyses indicated that patients with congestive heart failure (CHF) plus central sleep apnea (CSA) had shorter survival than those with just CHF, just sleep apnea (obstructive or central), or neither. Survival for those with obstructive sleep apnea (OSA) or CSA and no CHF was no different than for those with neither disorder. Follow-up analysis showed that for those with no CHF, neither CSA nor OSA shortened survival (p > 0.80). For those with CHF, having CSA shortened the life span with a hazard ratio of 1.66 (p = 0.012), but having OSA had no effect. Patients with CHF had more severe sleep apnea than those with no heart disease. CONCLUSIONS: This study does not clarify the issues of cause and effect, but does reinforce the strong associations between sleep apnea and heart disease in elderly men. These data suggest that people with coronary disease should be regarded as a risk group for sleep apnea.

Effect of light treatment on sleep and circadian rhythms in demented nursing home patients.

OBJECTIVES: To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light. DESIGN: Randomized controlled trial. SETTING: Two San Diego-area nursing homes. PARTICIPANTS: Seventy-seven (58 women, 19 men) nursing home residents participated. Mean age +/- standard deviation was 85.7 +/- 7.3 (range 60-100) and mean Mini-Mental State Examination was 12.8 +/- 8.8 (range 0-30). INTERVENTIONS: Participants were assigned to one of four treatments: evening bright light, morning bright light, daytime sleep restriction, or evening dim red light. MEASUREMENTS: Improvement in nighttime sleep quality, daytime alertness, and circadian activity rhythm parameters. RESULTS: There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups. Morning bright light delayed the peak of the activity rhythm (acrophase) and increased the mean activity level (mesor). In addition, subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment. CONCLUSION: Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust. These changes have the potential to be clinically beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable.

The timing of activity rhythms in patients with dementia is related to survival.

BACKGROUND: Older adults with dementia often have disruptions in circadian rhythms, including disruptions of the rest-activity rhythm. These disruptions are a product of internal neuronal activity and external environmental influences, both of which are deficient in dementia. However, the consequences of disturbed rhythms are unknown. This study examined the relationship between rest-activity rhythms and death in patients with dementia. METHODS: The authors recruited 149 older adults with dementia (104 women; mean age, 84.1 years) from nursing homes. Activity was recorded with wrist actigraphs from each participant for 3 days. Survival was determined by examining public death records. Cox proportional hazards models were used to determine which aspects of rest-activity rhythms were related to survival. RESULTS: The timing of each participant's rest-activity rhythm compared with a sample of persons without dementia was related to survival, such that those who more closely resembled the persons without dementia lived longer. CONCLUSIONS: Although rest-activity rhythms as a whole were not related to survival, the timing of the rhythm was. Patients with dementia appear to develop an abnormal timing of their rhythms, which is predictive of shorter survival. It may be possible to intervene with these patients to correct the timing of their rhythms and possibly prolong their lives.

Determinants of nasal CPAP compliance.

BACKGROUND: Obstructive sleep apnea is a prevalent condition with potentially serious medical and psychosocial consequences. Nasal continuous positive airway pressure (CPAP) is the treatment-of-choice and has been shown to reduce the frequency of nocturnal respiratory events, improve sleep architecture and decrease daytime sleepiness. Patient compliance with CPAP is disappointingly low. Previous studies examining determinants of CPAP compliance have limited the variables studied to patient (sociodemographic), disease status, and treatment variables, with few reliable determinants found. METHODS: The purpose of the current study was to investigate the relationship between objectively measured CPAP compliance and variables from social cognitive theory (SCT) and the transtheoretical model (TM). Scales that measure variables from each model were developed and reliability evaluated. The relationship between the SCT and TM variables and compliance at 1-month post-CPAP-fitting was prospectively evaluated on 51 first-time CPAP users. SCT and TM variables were measured on the day of CPAP-fitting, at 1-week post-CPAP-fitting, and at 1-month post-CPAP-fitting. RESULTS: SCT variables measured 1-week post-CPAP-fitting (R(2)=0.261, P=0.001) and TM variables measured 1-week post-CPAP-fitting (R(2)=0.17, P=0.002) accounted for a statistically significant amount of variance in objective CPAP compliance measured at 1 month. The decisional balance index (from TM) individually accounted for a significant amount of variance in objective CPAP compliance in the above analyses. CONCLUSIONS: The ability of these new behavior change scales to predict CPAP compliance provides us with a new direction of research to better understand factors associated with compliance. The principal advantage of these theory-driven and empirically validated scales are that they measure modifiable factors that can provide the basis for sound interventions to improve CPAP compliance.

PRC bisection tests.

This communication presents a new method for evaluating phase response curves (PRCs). A PRC describes the phase shifts produced in an oscillator by stimuli applied at different initial phase-states of that oscillator. In the PRC bisection tests, we repeatedly cut in half the circular distribution of the initial phase-states of the oscillator when stimuli are given. Empirically, we locate that optimal diameter which best bisects the circular distribution of phase responses into arcs of relative phase advance and phase delay. We compute a D score reflecting the success of the best bisection. The null hypothesis of a random distribution of phase responses by initial phase is tested with a Monte Carlo procedure, which computes Dr scores from random combinations of phase shifts with initial phases, thus determining the probability, given the null hypothesis, that the observed D score was from a random distribution. The bisection procedure can be extended to examine whether stronger phase shifts are produced in one phase response curve than in contrasting curves. Also, the bisection procedure yields an estimate of the inflection point of the phase response curve. A method is given to estimate the power of the PRC bisection test.

Sleep in older African Americans and Caucasians at risk for sleep-disordered breathing.

This study explored differences in sleep between older African Americans (AA) and Caucasians (CA) at risk for sleep-disordered breathing. Seventy AA and 70 CA were compared on ambulatory monitoring sleep variables and on self-reports on health and socioeconomic status (SES). After controlling for SES and health covariates, CA woke up significantly more often than AA (p = .018), but there were no other differences in sleep variables between the two groups. Time awake at night was related to being male, more depression, less walking, and lower income, whereas having more awakenings during the night was related to being CA, higher apnea-hypopnea index, and higher periodic leg movement index. Importance of inclusion of SES, health, and other covariates in studies exploring racial differences in sleep are discussed.

The sigmoidally transformed cosine curve: a mathematical model for circadian rhythms with symmetric non-sinusoidal shapes.

We introduce a family of non-linear transformations of the traditional cosine curve used in the modelling of biological rhythms. The non-linear transformation is the sigmoidal family, represented here by three family members: the Hill function, the anti-logistic function, and the arctangent function. These transforms add two additional parameters that must be estimated, in addition to the acrophase, MESOR, and amplitude (and period in some applications), but the estimated curves have shapes requiring many more than two additional harmonics to achieve the same fit when modelled by harmonic regression. Particular values of the additional parameters can yield rectangular waves, narrow pulses, wide pulses, and for rectangular waves (representing alternating 'on' and 'off' states) the times of onset and offset (hence duration, as when modelling the duration of the large night-time melatonin secretory epoch). We illustrate the sigmoidally transformed cosine curves, and compare them to harmonic regression modelling, in a sample of eight activity recordings made on patients in a nursing home.

Fatigue, sleep, and circadian rhythms prior to chemotherapy for breast cancer.

GOALS: Previous investigations have shown that women undergoing chemotherapy for breast cancer experience both disturbed sleep and fatigue. However, most of the previous research examined women either during or after chemotherapy. This study examined sleep, fatigue, and circadian rhythms in women with breast cancer before the start of chemotherapy. PATIENTS AND METHODS: Eighty five women with Stages I-IIIA breast cancer who were scheduled to begin adjuvant or neoadjuvant anthracycline-based chemotherapy participated. Each had sleep/wake activity recorded with actigraphy for 72 consecutive hours and filled out questionnaires on sleep, fatigue, depression, and functional outcome. MAIN RESULTS: On average, the women slept for about 6 h a night and napped for over an hour during the day. Sleep was reported to be disturbed and fatigue levels were high. Circadian rhythms were robust, but women who were more phase-delayed reported more daily dysfunction (p<0.01). CONCLUSIONS: The data from the current study suggest that the women with breast cancer likely experience both disturbed sleep and fatigue before the beginning of chemotherapy. Although their circadian rhythms are robust, breast cancer patients with more delayed rhythms experience more daily dysfunction secondary to fatigue. These data suggest that strategies to improve disturbed sleep and to phase-advance circadian rhythms prior to initiation of chemotherapy may be beneficial in improving daily function in breast cancer patients.

Adherence to continuous positive airway pressure treatment in patients with Alzheimer's disease and obstructive sleep apnea.

OBJECTIVE: This analysis examined whether patients with Alzheimer disease (AD) tolerate continuous positive airway pressure (CPAP). METHOD: Thirty patients with AD were randomized to CPAP or sham CPAP and completed sleep, depression, and quality-of-life questionnaires. Participants could choose to continue treatment after the trial. RESULTS: Patients wore CPAP for 4.8 hours per night. More depressive symptoms were associated with worse adherence (rS=-0.37; N=30, p<0.04). Patients who continued using CPAP had fewer depressive symptoms (t [19]=2.45, p=0.02) and better adherence (t [19]=2.32, p=0.03) during the trial. CONCLUSION: Patients with AD with obstructive sleep apnea can tolerate CPAP. Adherence and long-term use may be more difficult among those patients with more depressive symptoms.

The effect of sleep-disordered breathing on stages of sleep in patients with Alzheimer's disease.

Patients with Alzheimer's disease (AD) commonly have poor sleep and a high reported incidence of sleep-disordered breathing (SDB). This study examined how the presence of SDB affected sleep stages in AD patients. Sixty-six volunteers with mild - moderate AD underwent home polysomnography. Results showed that patients with SDB spent less of the night in REM sleep than those with no SDB, but there were no differences in other sleep stages. The findings suggest that the decreased amount of REM sleep may be due to the presence of AD and SDB. Treating these patients' SDB may increase their amount of REM sleep, which may result in improved daytime functioning. Controlled trials of SDB treatment in AD are needed to answer this question.