Sleep movements and respiratory coupling as a biobehavioral metric for early Alzheimer's disease in independently dwelling adults.

INTRODUCTION: Sleep disorder is often the first symptom of age-related cognitive decline associated with Alzheimer's disease (AD) observed in primary care. The relationship between sleep and early AD was examined using a patented sleep mattress designed to record respiration and high frequency movement arousals. A machine learning algorithm was developed to classify sleep features associated with early AD. METHOD: Community-dwelling older adults (N = 95; 62-90 years) were recruited in a 3-h catchment area. Study participants were tested on the mattress device in the home bed for 2 days, wore a wrist actigraph for 7 days, and provided sleep diary and sleep disorder self-reports during the 1-week study period. Neurocognitive testing was completed in the home within 30-days of the sleep study. Participant performance on executive and memory tasks, health history and demographics were reviewed by a geriatric clinical team yielding Normal Cognition (n = 45) and amnestic MCI-Consensus (n = 33) groups. A diagnosed MCI group (n = 17) was recruited from a hospital memory clinic following diagnostic series of neuroimaging biomarker assessment and cognitive criteria for AD. RESULTS: In cohort analyses, sleep fragmentation and wake after sleep onset duration predicted poorer executive function, particularly memory performance. Group analyses showed increased sleep fragmentation and total sleep time in the diagnosed MCI group compared to the Normal Cognition group. Machine learning algorithm showed that the time latency between movement arousals and coupled respiratory upregulation could be used as a classifier of diagnosed MCI vs. Normal Cognition cases. ROC diagnostics identified MCI with 87% sensitivity; 89% specificity; and 88% positive predictive value. DISCUSSION: AD sleep phenotype was detected with a novel sleep biometric, time latency, associated with the tight gap between sleep movements and respiratory coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Diagnosed MCI was associated with sleep fragmentation and arousal intrusion.

Melatonin for sleep disturbances in Parkinson's disease.

BACKGROUND AND PURPOSE: Many patients with Parkinson's disease (PD) experience sleep-related symptoms. Studies in other populations indicate that melatonin can increase sleep efficiency, decrease nighttime activity, and shorten sleep latency, but there has been little research on the use of melatonin in PD. The purpose of this study was to compare the effects of two doses of melatonin to placebo on sleep, daytime sleepiness, and level of function in patients with PD who complained of sleep disturbances. PATIENTS AND METHODS: A multi-site double-blind placebo-controlled cross-over trial was employed; 40 subjects completed the 10-week protocol. There was a 2-week screening period, 2-week treatment periods, and 1-week washouts between treatments. Nocturnal sleep was assessed by actigraphy and diaries, whereas daytime sleepiness and function were assessed by the Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), and General Sleep Disturbance Scale (GSDS). RESULTS: Repeated measures analysis of variance revealed a significant improvement in total nighttime sleep time during the 50 mg melatonin treatment compared to placebo. There was significant improvement in subjective sleep disturbance, sleep quantity, and daytime sleepiness during the 5 mg melatonin treatment compared to placebo as assessed by the GSDS. CONCLUSIONS: Although we found a statistically significant improvement in actigraphically measured total sleep time on 50 mg melatonin compared to 5 mg or placebo, this small improvement (10 min) may not be clinically significant. However, the significant improvement found in subjective sleep disturbance suggests that these modest effects may be clinically relevant in this patient population.

A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease.

OBJECTIVES: To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease. DESIGN: A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer's Disease Cooperative Study. Subjects with Alzheimer's disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin. SETTING: Private homes and long-term care facilities. PARTICIPANTS: 157 individuals were recruited by 36 Alzheimer's disease research centers. Subjects with a diagnosis of Alzheimer's disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver. MEASUREMENTS: Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data. RESULTS: No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups. CONCLUSIONS: Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer's disease.

Outcomes of pain in frail older adults with dementia.

OBJECTIVES: To describe the outcomes of pain in cognitively impaired older adults in a Program of All-inclusive Care for older people (PACE) setting and to determine whether pain and psychotropic drug use, behavioral disturbances, hospital, nursing facility, and emergency department use, or mortality increases with the level of pain reported. DESIGN: Retrospective review of an observational cohort of patients with dementia. SETTING: A first-generation PACE program located in Portland, Oregon. Patients with the diagnosis of dementia had been assessed for pain in a prior study. PARTICIPANTS: One hundred fifty-four cognitively impaired subjects. MEASUREMENTS: Standardized pain assessments were administered to cognitively impaired subjects between June and October 1998. After the pain assessment, information about mortality and healthcare use, including use of medication, was collected and analyzed. Subjects who reported moderate to severe pain were compared with demented subjects who reported no or mild pain. RESULTS: There were no differences in patient characteristics (age, sex, functional limitations, disruptive behaviors, and incontinence), medications (pain and psychotropic), use (hospital, nursing home, or emergency department visit), or mortality by level of pain alone or by levels of pain and dementia together. CONCLUSIONS: The study did not demonstrate that a single point-in-time measurement of pain in demented persons was associated with an increased rate of behavioral problems, narcotic use, or hospital or emergency department use over the following year. Prospective studies are needed that measure pain over time to determine more accurately the relationship between pain and negative outcomes in dementia.

Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease.

This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.

Pain Assessment for the Dementing Elderly (PADE): reliability and validity of a new measure.

OBJECTIVES: To establish the reliability and validity of a measure to assess pain in individuals with advanced dementia. DESIGN: Sixty-five residents of long-term care facilities were assessed using a new rating tool, the Pain Assessment for the Dementing Elderly (PADE), in two separate studies: (1) Residents were assessed simultaneously by two different raters, at Time 1 and 2, to establish interrater reliability, stability, and internal consistency. (2) Validity was established by assessing the correlation between an agitation scale and the PADE; by comparing groups with pain as a significant clinical factor (as assessed by an independent rater) versus not a significant factor, and by assessing individuals receiving versus not receiving psychoactive medications. SETTING: Four different long-term care facilities, three skilled nursing facilities, and a locked dementia assisted-living facility. PARTICIPANTS: Twenty-five residents of long-term care facilities with advanced levels of dementia in Study 1, and 40 residents with similar level of dementia in Study 2; 42% of the total sample were rated as having significant painful conditions. MEASUREMENTS: For Study 1, the PADE was administered; for Study 2, the PADE and the Cohen-Mansfield Agitation Inventory (CMAI) were administered. RESULTS: Reliability coefficients were adequate (interrater = 0.54-0.95; stability = 0.70-0.98; and internal consistency = 0.24-0.88). Validity coefficients were likewise encouraging, with the PADE demonstrating the expected relationship with a measure of agitation. The PADE also differentiated between groups that were independently judged to suffer clinically problematic pain versus those who were not. CONCLUSION: The PADE is a reliable and valid tool to assess pain in dementing elderly residents of long-term care facilities.

A method for classification of movements in bed.

Sleep is characterized by episodes of immobility interrupted by periods of voluntary and involuntary movement. Increased mobility in bed can be a sign of disrupted sleep that may reduce sleep quality. This paper describes a method for classification of the type of movement in bed using load cells installed at the corners of a bed. The approach is based on Gaussian Mixture Models using a time-domain feature representation. The movement classification system is evaluated on data collected in the laboratory, and it classified correctly 84.6% of movements. The unobtrusive aspect of this approach is particularly valuable for longer-term home monitoring against a standard clinical setting.

Detection of movement in bed using unobtrusive load cell sensors.

Quality of sleep is an important attribute of an individual's health state and its assessment is therefore a useful diagnostic feature. Changes in the patterns of motor activities during sleep can be a disease marker, or can reflect various abnormal physiological and neurological conditions. Presently, there are no convenient, unobtrusive ways to assess quality of sleep outside of a clinic. This paper describes a system for unobtrusive detection of movement in bed that uses load cells installed at the corners of a bed. The system focuses on identifying when a movement occurs based on the forces sensed by the load cells. The movement detection approach estimates the energy in each load cell signal over short segments to capture the variations caused by movement. The accuracy of the detector is evaluated using data collected in the laboratory. The detector is capable of detecting voluntary movements in bed while the subjects were awake, with an average equal error rate of 3.22% (+/-0.54). Its performance is invariant with respect to the individual's characteristics, e.g., weight, as well as those of the bed. The simplicity of the resulting algorithms and their relative insensitivity to the weight and height of the monitored individual make the approach practical and easily deployable in residential and clinical settings.

Characterizing sleep problems in persons with Alzheimer's disease and normal elderly.

We retrospectively analyzed sleep disturbance symptoms and estimated time in bed from the intake interviews of 399 healthy, non-demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to identify what symptoms might underlie an individual's perception of 'sleep problems' and to determine if these were consistent within, and across, our two cohorts. We stratified each cohort according to whether or not they (or their caregiver) indicated that they had a 'sleep problem', and compared the frequency and endorsement rates of each of 21 sleep disturbance symptoms across those who did or did not endorse 'sleep problem'. For less than half of the symptoms in persons with AD, and a quarter of those in NDE, endorsement rates were significantly different depending on whether the reporter (or their sleep partner) did or did not report a sleep problem. Differences in mean frequency ratings between individuals reporting sleep problems relative to those not reporting were observed on 10 symptoms in both cohorts; six of these were the same symptom for both cohorts. When persons with subjective sleep problems in the AD and NDE cohorts were compared, only four of 21 symptoms were endorsed in one and not the other; two symptoms were significantly more frequent in one cohort than the other. Thus, within cohorts, the differences between persons with and without 'sleep problems' were relatively pronounced while the main differences in specific sleep-related symptoms between AD and NDE were not. Observed between-cohort differences appear to be driven by who is reporting, and the high prevalence of daytime sleeping in AD. Within-cohort differences reflect a clear distinction between persons with and without sleep problems, regardless of the reporter.

Symptoms of sleep disturbance in persons with Alzheimer's disease and normal elderly.

We retrospectively analyzed sleep time and sleep disturbance symptoms in 399 healthy, non-demented elderly (NDE) and 263 persons with a diagnosis of possible (n = 53) or probable (n = 210) Alzheimer's disease (AD). Our primary objective was to determine differences in subjective sleep disturbance between these samples. Secondary objectives were to determine if subjects with time in bed (TIB) < or =6 h per night reported more sleep disturbance and whether sleep complaints were associated with more severe cognitive and/or functional impairment. The prevalence of 'sleep problems' (a single item) was significantly lower in NDE (18.3%) than AD (27.6%), and the proportions of each cohort reporting TIB < or =6 h per night were very low (NDE: 6.0%; AD: 3.5%) and not significantly different. Less TIB was correlated with better cognitive function for AD (P < 0.01), and cognition and function were significantly worse for AD subjects with estimates of >6 h of TIB compared with those with estimates of < or =6 h (P < 0.05). Greater sleep disturbance was correlated with greater functional impairment in both cohorts; but only in AD did greater estimated TIB also correlate with greater functional impairment (all P < 0.05). In general, estimated TIB was not associated with mood in either cohort; however, in both cohorts depression was significantly associated with sleep disturbance symptoms and was significantly worse in those who reported having 'sleep problems'. There was no association between subjective perception of 'sleep problems', the number and frequency of sleep disturbance symptoms, and estimated TIB in either group.

The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer's disease.

The Sleep Disorders Inventory (SDI) is an expanded version of one item of the Neuropsychiatric Inventory (NPI). It describes the frequency, severity, and caregiver burden of sleep-disturbed behaviors during a period prior to its administration. We carried out post hoc analyses on baseline responses to the SDI in 104 persons with Alzheimer's disease (AD) and live-in caregivers who had been recruited for a trial of melatonin in the treatment of sleep disturbance. These patient-participants averaged <7 h of sleep per night, measured by actigraph (sleep disturbance), for the 2-3-week period prior to administration of SDI. Data were from the 2 weeks prior to the baseline visit (SDI, NPI) including actigraph-derived sleep variables and 2 weeks' worth of sleep quality ratings (SQR) kept in a diary by caregivers, plus Mini-Mental State Examination and activities of daily living assessment at baseline. The prevalence of sleep disorder symptoms ranged from 34% (waking up at night thinking it is daytime) and 82% (getting up during the night). Worse SDI scores were associated with worse cognitive, functional, and behavioral status, but not with sex, age, education or duration of dementia. SDI scores were significantly worse in individuals meeting independently established criteria for a diagnosis of 'sleep disturbance' (<6 h total sleep time per night) whereas demographic variables and scores reflecting cognition and function were not significantly different across this grouping. The SDI covers a wide range of sleep behaviors and provides information independent of sleep time and SQR.