Sonia Ancoli-Israel - US grants

Wandering at night, agitation, disturbed sleep and night/day reversal are common problems for demented elderly and often lead to institutionalization. Learning more about the correlates of agitation, wandering and sundowning and their relation to sleep, and examining techniques to improve these symptoms might postpone, if not avoid, institutionalization. Our interest in agitation grew out of our prior years of experience working with nursing home patients. In the process of examining the effect of light treatment on sleep consolidation, we observed the effect light seemed to have on behavior. We now propose to study agitation more systematically and examine a behavioral treatment designed to attenuate agitated behavior. Our specific aims are to 1) evaluate the effect of light therapy on agitated behavior; 2) determine within patients the degree of agitation occurring at night vs. that occurring during the day; 3) determine the percent of patients with primarily evening agitation and the percent with primarily morning agitation; 4) examine the relationship between agitated behaviors and light exposure; 5) examine the relationship between agitated behaviors and sleep; 6) examine the relationship between agitated behaviors and sleep disordered breathing. Each patient will have sleep/wake behavior and light exposure measured with an Actillume recorder; each will have sleep, breathing and blood oxygen saturation levels recorded for one night; each will have agitation measures recorded four times an hour for 24-hour periods. Data for the aims 2-6 will be collected before intervention begins. Patients will then be randomly assigned to one of three treatment groups: Bright light exposure in the morning, dim light exposure in the morning or bright light exposure in the evening. The intervention trials will help determine whether agitation can be reduced by these approaches. The results will both help us understand the correlates of agitation and suggest treatment options.

Sleep apnea is a serious disorder characterized by complete cessations of respiration during sleep. Current work indicated that 35% of VA inpatients >60 years old have more that 5 apneas per hour of sleep and 13% have over 20 apneas per hour of sleep. Little is known about the natural history, clinical implications, or risks of such wide-spread apnea. The first goal of this study is to describe the natural history and progression of sleep apnea and periodic leg movements in sleep (PLMS, a disorder of leg kicks during the night). Seventy-five elderly VA patients, already recorded between 1987-1989, and 37 independently-living elderly who have been previously recorded, will be rerecorded every two years for a four-year period. Each person will be recorded with a modified Medilog/Respitrace portable recorder and with oximetry for two nights. In addition, sleep symptoms and medical history will be followed. Clinically, we need to know how commonly a patient who was found to have significant sleep apnea continues to have apnea and related morbidity. The second goal is to examine the relationships between sleep apnea and mortality by following 700 elderly subjects who have been prospectively recorded in three studies. These subjects' survival will be followed to see if apnea predicts increased mortality.

Fatigue is described as a major complaint in patients undergoing chemotherapy. Yet it is unknown whether the fatigue has any relationship to the quality or quantity of sleep or to the sleep/wake circadian rhythm cycle. One of the easiest circadian rhythms to measure is sleep/wake activity. Sleep may also play an important role in the quality of life of these patients. If patients with synchronized rhythms show better tolerance to treatment, then synchronizing the rhythms with light therapy before the start of therapy would be encouraged. Before treatment studies or synchronization studies can be implemented however, more understanding is needed about the relationship between fatigue and sleep, about the normal circadian rhythms in cancer patients and what happens to rhythms during traditional therapy. Current technology allows for non-invasive, ambulatory measurements of circadian rhythms and sleep/wake activity. We propose to study sleep/wake activity cycles in outpatients with breast cancer to examine the relationship between fatigue experienced during the day with sleep/wake cycles and with the quality and quantity of sleep recorded at night; to examine the effect of fatigue and desynchronized sleep/wake rhythms on quality of life and mood (e.g., depression) during multiple cycles of treatment; to examine whether sleep/wake rhythms influence a patient's tolerance to treatment; to examine the effect of chemotherapy on sleep/wake rhythms and quality and quantity of sleep, over the time course of multiple cycles of chemotherapy; to examine the relationship between light exposure and circadian rhythms. This will be accomplished by placing Actillumes on patients for 72-hour periods each week of cycle one and cycle four of chemotherapy. At each visit questionnaires evaluating sleep, fatigue, depression and quality of life will be administered. In addition, since many of these women will be older, each woman will have a complete polysomnogram to rule out sleep disordered breathing and periodic limb movements in sleep. Results will provide a scientific basis for future intervention studies, particularly studies with light therapy which can re-synchronize rhythms.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims: 1) Examine the effect of chemotherapy on cognition - hypothesize impairment. 2) Locate brain areas associated with impaired cognition in breast CA patients undergoing chemotheraphy 3) Examine relation between cognitive impairment and fatigue 4) examine realtionship betwen cognitive impairment and sleep/circadian rhythms 5) examine relationship between inflammatory markers and cognitive function, sleep &fatigue, before during and after chemotherapy.

DESCRIPTION (provided by applicant): Patients treated with chemotherapy complain of decreased cognitive functioning before and during chemotherapy, as well as for some years after the end of therapy. Objective measures of cognitive functioning confirm that a large percentage of patients receiving chemotherapy show at least acute decrements in multiple domains of cognitive test performance. This phenomenon has been termed "chemobrain." Understanding the cause of the cognitive deficits is critical as these patients require increased care, experience impaired decision making ability, experience decreased quality of life and express concern about their ability to maintain employment. Fatigue and problems sleeping are also major complaints in this population, particularly in patients with breast cancer. Yet whether chemobrain is related just to the chemotherapy, or might be secondary to fatigue and/or sleep and circadian rhythm problems has not yet been explored. Clarification of the role of sleep disturbances, hormonal changes, anxiety and depression, and other proximal causes of cognitive impairment in chemotherapy patients may be helpful in identifying potential targets for secondary intervention. The specific aims are: to examine how much cognitive impairment occurs during chemotherapy and one year after the start of chemotherapy compared to before the start of treatment; to examine the relationship between cognitive impairment and fatigue; to examine the relationship between cognitive impairment and sleep and circadian rhythms; and to examine the relationship between inflammatory markers, cognitive functioning and sleep. Over 5 years, 80 women with breast cancer and 80 controls (women with no history of any cancer) will be studied. Women will have their sleep recorded for three days with actigraphy, a complete neuropsychological test battery, have blood drawn for inflammatory markers and complete questionnaires on fatigue, sleep, menopausal status, quality of life, depression, and anxiety. These procedures will be repeated before the start of chemotherapy, during week 2 of cycle 4 of chemotherapy and one year after chemotherapy. Control women will be tested at the same time points. Each woman will also have a complete overnight sleep recording. The reported phenomena of chemobrain will be examined to see if it is related to the complaint of fatigue or sleep disruptions, both of which are known to contribute to decreases in cognitive functioning.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AIM 1: Examine the effect of CPAP treatment on SDB and sleep in patients with SDB and PDD. Hypothesis 1: SDB and sleep will improve with CPAP treatment (i.e., the number of respiratory events and the number of desaturations will decrease and sleep will become less fragmented with fewer arousals as measured by polysomnography [PSG]) as compared to shamCPAP treatment. AIM 2: Examine the effect of CPAP treatment on daytime sleepiness, cognition, overall quality of life and mood in patients with SDB and PDD. Hypothesis 2: Improved sleep (defined by fewer arousals in nighttime PSG) and reduction of SDB (fewer respiratory events and decreased numbers of desaturations) following CPAP treatment will result in less daytime sleepiness (as measured by sleep latency on the multiple sleep latency test and subjective reports on the Epworth Sleepiness Scale), improvement in cognitive functioning (particularly in the areas of attention/vigilance, executive functioning and psychomotor speed), fewer depressive symptoms and improved quality of life as measured by standardized questionnaires.