Previous studies have demonstrated both clinical and neurochemical similarities between Parkinson’s disease (PD) and narcolepsy. The intrusion of REM sleep into the daytime remains a cardinal feature of narcolepsy, but the importance of these intrusions in PD remains unclear. In this study we examined REM sleep during daytime Maintenance of Wakefulness Testing (MWT) in PD patients.
Patients spent 2 consecutive nights and days in the sleep laboratory. During the daytime, we employed a modified MWT procedure in which each daytime nap opportunity (4 per day) was extended to 40 minutes, regardless of whether the patient was able to sleep or how much the patient slept. We examined each nap opportunity for the presence of REM sleep and time to fall asleep.
Eleven of 63 PD patients studied showed 2 or more REM episodes and 10 showed 1 REM episode on their daytime MWTs. Nocturnal sleep characteristics and sleep disorders were unrelated to the presence of daytime REM sleep, however, patients with daytime REM were significantly sleepier during the daytime than those patients without REM. Demographic and clinical variables, including Unified Parkinson’s Disease Rating Scale motor scores and levodopa dose equivalents, were unrelated to the presence of REM sleep.
A sizeable proportion of PD patients demonstrated REM sleep and daytime sleep tendency during daytime nap testing. These data confirm similarities in REM intrusions between narcolepsy and PD, perhaps suggesting parallel neurodegenerative conditions of hypocretin deficiency.
Parkinson’s Disease; Narcolepsy; REM Sleep
Examination of spontaneously occurring phasic muscle activity from the human polysomnogram may have considerable clinical importance for patient care, yet most attempts to quantify the detection of such activity have relied upon laborious and intensive visual analyses. We describe in this study innovative signal processing approaches to this issue.
We examined multiple features of surface electromyographic signals based on 16,200 individual 1-second intervals of low impedance sleep recordings. We validated which of those features most closely mirrored the careful judgments of trained human observers in making discriminations of the presence of short-lived (100-500 msec) phasic activity, and also examined which features provided maximal differences across 1-second intervals and which features were least susceptible to residual levels of amplifier noise.
Our data suggested particularly promising and novel features (e.g., Non-linear energy, 95th percentile of Spectral Edge Frequency) for developing automated systems for quantifying muscle activity during human sleep.
The EMG signals recorded from surface electrodes during sleep can be processed with techniques that reflect the visually based analyses of the human scorer but also offer potential for discerning far more subtle effects, Future studies will explore both the clinical utility of these techniques and their relative susceptibility to and/or independence from signal artifacts.
Electromyography; Sleep; Muscle Activity; Phasic Activity; Polysomnography; Computer Detection
Many patients with idiopathic Parkinson’s disease experience difficulties maintaining daytime alertness. Controversy exists regarding whether this reflects effects of anti-Parkinsonian medications, the disease itself or other factors such as nocturnal sleep disturbances. In this study we examined the phenomenon by evaluating medicated and unmedicated Parkinson’s patients with objective polysomnographic measurements of nocturnal sleep and daytime alertness.
Patients (n = 63) underwent a 48-hour laboratory-based study incorporating 2 consecutive nights of overnight polysomnography and 2 days of Maintenance of Wakefulness Testing. We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables and class and dosage of anti-Parkinson’s medications.
Results indicated that: 1) relative to unmediated patients, all classes of dopaminergic medications were associated with reduced daytime alertness and this effect was not mediated by disease duration or disease severity; 2) increasing dosages of dopamine agonists were associated with less daytime alertness, whereas higher levels of levodopa were associated with higher levels of alertness. Variables unrelated to Maintenance of Wakefulness Test defined daytime alertness included age, sex, years with diagnosis, motor impairment score and most nocturnal sleep variables.
Deficits in objectively assessed daytime alertness in Parkinson’s disease appear to be a function of both the disease and the medications and their doses utilized. The apparent divergent dose-dependent effects of drug class in Parkinson’s disease are anticipated by basic science studies of the sleep/wake cycle under different pharmacological agents.
Parkinson’s Disease; Daytime Alertness; Sleep; Maintenance of Wakefulness Test; Dopaminergic Treatment
Periodic Leg Movements in Sleep (PLMS) are non-epileptiform, repetitive movements of the lower limbs that have been associated with apparent dopamine deficiency. We hypothesized that elderly patients with a disease characterized primarily by dopamine depletion (Parkinsonism) would have higher rates of PLMS than aged matched controls or a different neurodegenerative condition not primarily involving a hypodopaminergic state, Alzheimer’s Disease (AD).
We compared rates of PLMS derived from in-lab overnight polysomnography in patients with Parkinsonism (n = 79), AD (n = 28), and non-neurologically impaired, community-based controls (n = 187).
Parkinsonian patients not receiving levo-dopa had significantly higher rates of PLMS than did Parkinsonian patients receiving levo-dopa, as well as higher rates than seen in AD and controls. Other medications did not appear to exert the pronounced effect of levo-dopa on PLMS in this Parkinsonian patient population. The symptom of leg kicking was reported more frequently in Parkinsonism, and it was associated with higher rates of PLMS. Caregiver reported leg kicking was unrelated to PLMS in AD.
Results are broadly compatible with a dopaminergic hypothesis for PLMS in Parkinsonism. The clinical significance of the negative findings in AD patient requires further investigation.
Parkinsonism; Alzheimer’s Disease; Periodic Leg Movements in Sleep; Restless Legs Syndrome; Willis-Ekbom Disease
The Phasic Electromyographic Metric (PEM) has been recently introduced as a sensitive indicator to differentiate Parkinson’s Disease (PD) patients from controls, non-PD patients with a history of Rapid Eye Movement Disorder (RBD) from controls, and PD patients with early and late stage disease. However, PEM assessment through visual inspection is a cumbersome and time consuming process. Therefore, a reliable automated approach is required so as to increase the utilization of PEM as a reliable and efficient clinical tool to track PD progression. In this study an automated method for the detection of PEM is presented, based on the use of signal analysis and pattern recognition techniques. The results are promising indicating that an automatic PEM identification procedure is feasible.
Previous studies suggested that sleep apnea is associated with neurocognitive impairments but did not examine populations most likely to have clinically relevant impairments. Cross-sectional, retrospective analyses were performed on 108 patients (65 with Mild Cognitive Impairment, 43 with dementia) seen in an academic medical center. Results indicated that severity of oxygen desaturation was associated with cognitive impairments in attention and executive function domains, even after controlling for age, sex, education and depressive symptoms. Strength of associations was influenced by cardiovascular disease. Screening for nocturnal oxygen desaturation may be a useful procedure to assess for a potentially reversible cause of cognitive impairment.
Sleep Apnea; Cardiovascular Disease; Pulse Oximetry; Cognitive Disorders; Geriatrics; Neuropsychology
Restless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.
137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).
Mean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with log CRP (r(129) = 0.19, p = 0.03). Those patients with at least 45 PLMs/hour had an odds ratio of 3.56 (95% CI 1.26 to 10.03, p = 0.02, df = 1) for having elevated CRP compared to those with fewer than 45 PLMs/hour. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ≥ 45 PLMs/hour was 8.60 (95% CI 1.23 to 60.17, p = 0.03, df = 10).
PLMs are associated with increased inflammation, such that those RLS patients with at least 45 PLMs/hour had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.
C-reactive protein; periodic leg movements of sleep; restless legs syndrome; interleukin-6; tumor necrosis factor alpha; cardiovascular disease
To describe the prevalence and correlates of sleep disturbances among women who retrospectively reported sleep disturbance prior to their myocardial infarction (MI).
MI is frequently unrecognized in women because they may have only vague symptoms, such as sleep disturbance. Describing correlates of sleep disturbance prior to MI may assist in recognizing women at risk for coronary heart disease.
Secondary analysis of dataset derived from 15 sites.
Of 1270 women experiencing initial MI, 632 reported new onset of or worsening sleep disturbance before MI. Prevalence was similar across racial groups. Women reporting prodromal sleep disturbance were more likely to be older, heavier, and report cognitive changes (aOR= 1.47), new or increasing anxiety (aOR= 2.21), and unusual fatigue (aOR= 2.16).
Subjective report of sleep disturbance preceding MI appear to be prevalent in women of all races and may be an important warning sign for MI in women.
cardiovascular disease; cognitive disorders; sleep disturbance; menopause; women
Working memory is essential to higher order cognition (e.g. fluid intelligence) and to performance of daily activities. Though working memory capacity was traditionally thought to be inflexible, recent studies report that working memory capacity can be trained and that offline processes occurring during sleep may facilitate improvements in working memory performance. We utilized a 48-h in-laboratory protocol consisting of repeated digit span forward (short-term attention measure) and digit span backward (working memory measure) tests and overnight polysomnography to investigate the specific sleep-dependent processes that may facilitate working memory performance improvements in the synucleinopathies. We found that digit span backward performance improved following a nocturnal sleep interval in patients with Parkinson's disease on dopaminergic medication, but not in those not taking dopaminergic medication and not in patients with dementia with Lewy bodies. Furthermore, the improvements in patients with Parkinson's disease on dopaminergic medication were positively correlated with the amount of slow-wave sleep that patients obtained between training sessions and negatively correlated with severity of nocturnal oxygen desaturation. The translational implication is that working memory capacity is potentially modifiable in patients with Parkinson's disease but that sleep disturbances may first need to be corrected.
consolidation; sleep; working memory; training; Parkinson's disease; dementia with Lewy bodies
In this study, restless legs syndrome (RLS) risk factors, RLS-associated behaviors, and the ability to understand and answer an RLS diagnostic interview were investigated. In 23 older adults with early to moderate dementia and nighttime sleep disturbance, the most common risk factors for RLS were a periodic leg movement sleep index > 15 (54.55%), based on polysomnography, and use of selective serotonin reuptake inhibitors (SSRis) (34.78% ). The most common RLS-associated behaviors were repetitious mannerisms (56.52%) and general restlessness (34.78% ), according to direct observation from research assistants. Finally, older adults with early to moderate dementia were unable to understand and reliably answer the RLS diagnostic interview. Older persons with mild to moderate dementia and sleep disturbance may require objective diagnostics to identify RLS.
Pulmonary function abnormalities in Parkinson’s disease (PD) might predispose patients to obstructive sleep apnea (OSA) and daytime sleepiness. Fifty-five idiopathic PD patients (mean age = 63.9) underwent three consecutive nights of in-laboratory polysomnography on their usual dopaminergic medications. Sleep apnea severity was compared to published, normative, population-based data from the Sleep Heart Health Study. Demographic and clinical data were compared in patients with and without OSA. The apnea-hyponea index (AHI) was stable across nights in PD patients, and was not different between PD patients and normative controls. Epworth Sleepiness Scale scores, Body Mass Index, and snoring did not correlate with AHI. Severity of OSA is stable across multiple nights in PD patients. Rates of OSA in PD are similar to those seen in the general population. Daytime sleepiness, snoring, and obesity may not be helpful in identifying OSA in PD.
Parkinson’s Disease; Obstructive Sleep Apnea; Excessive Daytime Sleepiness
The absence of atonia during rapid eye movement (REM) sleep and dream-enactment behavior (REM sleep behavior disorder [RBD]) are common features of sleep in the alpha-synucleinopathies. This study examined this phenomenon quantitatively, using the phasic electromyographic metric (PEM), in relation to clinical features of idiopathic Parkinson disease (PD). Based on previous studies suggesting that RBD may be prognostic for the development of later parkinsonism, we hypothesized that clinical indicators of disease severity and more rapid progression would be related to PEM.
A cross-sectional convenience sample of 55 idiopathic PD patients from a movement disorders clinic in a tertiary care medical center underwent overnight polysomnography. PEM, the percentage of 2.5-second intervals containing phasic muscle activity, was quantified separately for REM and non-REM (NREM) sleep from 5 different electrode sites.
Higher PEM rates were seen in patients with symmetric disease, as well as in akinetic-rigid versus tremor-predominant patients. Men had higher PEM relative to women. Results occurred in all muscle groups in both REM and NREM sleep.
Although our data were cross-sectional, phasic muscle activity during sleep suggests disinhibition of descending motor projections in PD broadly reflective of more advanced and/or progressive disease. Elevated PEM during sleep may represent a functional window into brainstem modulation of spinal cord activity and is broadly consistent with the early pathologic involvement of non-nigral brainstem regions in PD, as described by Braak.
Nocturnal urination (nocturia) is such a commonplace occurrence in the lives of many older adults that it is frequently overlooked as a potential cause of sleep disturbance.
We examined the prevalence of nocturia and examined its role in self-reported insomnia and poor sleep quality in a survey of 1,424 elderly individuals, ages 55–84. Data were derived from a 2003 National Sleep Foundation telephone poll conducted in a representative sample of the United States population who underwent a 20-minute structured telephone interview. Nocturia was not a focus of the survey, but data collected relevant to this topic allowed examination of relevant associations with sleep.
When inquired about in a checklist format, nocturia was listed as a self-perceived cause of nocturnal sleep “every night or almost every night” by 53% of the sample, which was over four times as frequently as the next most often cited cause of poor sleep, pain (12%). In multivariate logistic models, nocturia was an independent predictor both of self-reported insomnia (75% increased risk) and reduced sleep quality (71% increased risk), along with female gender and other medical and psychiatric conditions.
Nocturia is a frequently overlooked cause of poor sleep in the elderly and may warrant targeted interventions.
Aging; Health Survey; Nocturia; Sleep Initiation and Maintenance Disorders; Prostatism; Falls
Sleep Disordered Breathing (SDB) is highly prevalent in elderly populations and is thought to reflect, at least in part, age-dependence. Several studies suggest that SDB in elderly populations may hold different functional outcomes relative to SDB in middle-aged populations. Risk factors for SDB specific for the elderly remain uncertain. In this report, we examined changes in SDB, body weight and pulmonary function in 103 individuals over an average interval of 7 years to determine whether changes in these measures covaried. In-lab polysomnography was performed on members of an elderly cohort (Bay Area Sleep Cohort) on two separate occasions (Time 1, Time 2) with multiple nights of measurement typically made on each occasion. Results indicated that: a) SDB progressed over time in both men and women; b) changes in body weight were unrelated to the progression in SDB; c) relative declines in lung volumes (Forced Vital Capacity, Forced Expiratory Volume in 1.0 second) were associated with relative increases in SDB, with the effects slightly stronger in men. These data suggest that age-dependence in one commonly ascribed aging biomarker (lung function) were coupled to increments in SDB. Maintenance of healthy lung function into old age may confer some protective benefits in the development of age-dependent SDB.
Periodic leg movement in sleep; restless legs syndrome; nocturnal wandering; anemia; Alzheimer's Disease; Parkinson's Disease
Regular exercise can improve sleep quality, but for whom and by what means this occurs remain unclear. We examined moderators and mediators of objective sleep improvements in a 12-month randomized controlled trial among initially underactive midlife and older adults reporting mild/moderate sleep complaints. Participants (N=66, 67% women, 55–79 years) were randomized to moderate-intensity exercise or health education control. Putative moderators were gender, age, and baseline physical function, self-reported global sleep quality, and physical activity levels. Putative mediators were changes in BMI, depressive symptoms, and physical function at 6 months. Objective sleep outcomes measured by in-home PSG were percent time in Stage 1 sleep, percent time in Stage 2 sleep, and number of awakenings during the first third of sleep at 12 months. Baseline physical function and sleep quality moderated changes in Stage 1 sleep; individuals with higher initial physical function (p=0.01) and poorer sleep quality (p=0.03) had greater improvements. Baseline physical activity level moderated changes in Stage 2 sleep (p=0.04) and number of awakenings (p=0.01); more sedentary individuals had greater improvements. Decreased depressive symptoms (CI:−1.57 to −0.02) mediated change in Stage 1 sleep. Decreased depressive symptoms (CI: −0.75 to −0.01), decreased BMI (CI:−1.08 to −0.06), and increased physical function (CI:0.01 to 0.72) mediated change in number of awakenings. In conclusion, initially less active individuals with higher initial physical function and poorer sleep quality improved the most. Affective, functional, and metabolic mediators specific to different parameters of sleep architecture were suggested. Collectively, the results indicate strategies to more efficiently treat poor sleep through exercise in older adults.
objective sleep; exercise; physical activity; multiple mediation; moderation
Sleep plays a vital role in physical and mental functioning. It is increasingly recognized that disturbed sleep is a highly prevalent and chronic condition that merits greater awareness due to the wide-ranging and serious repercussions associated with it. Nocturia is one of the causes of sleep disturbance and has been shown to impair functioning, quality of life, health and productivity, with those experiencing two or more voids per night reporting significant ‘bother’. Nocturia warrants full consideration as a significant target for intervention, aiming to reduce the burden of disturbed sleep on individuals, families and society. Currently however, a definitive evaluation of the most relevant sleep endpoints in nocturia therapy is lacking. One endpoint often used is the duration of the initial sleep period, which when evaluated in combination with the number of voiding episodes per night might be an indication of the severity of sleep disruption in patients with nocturia.
nocturia; sleep; insomnia; quality of life
Sleep interventions have rarely explored reductions in night-to-night fluctuations (i.e., intra-individual variability [IIV]) in sleep, despite the negative impacts of such fluctuations on affective states and cognitive and physical symptoms. In a community-based randomized controlled trial we evaluated whether physical exercise reduced IIV in self-rated sleep outcomes among middle-aged and older adults with sleep complaints. Under-active adults 55 years and older (N=66, 67% women) with mild to moderate sleep complaints were randomized to 12mos of a moderate-intensity endurance exercise (n=36) or a health education control group (n=30). Daily sleep logs, Pittsburgh Sleep Quality Index (PSQI), and in-home polysomnographic sleep recordings (PSG) were collected at baseline, 6mos, and 12mos. Sleep log-derived means and IIV were computed for sleep-onset latency (SOL), time in bed (TIB), feeling rested in the morning, number of nighttime awakenings, and wake after final awakening (WAFA). Using intent-to-treat methods, at 6mos no differences in IIV were observed by group. At 12mos, SOL-based IIV was reduced in the exercise group compared to the control (difference=23.11, 95% CI: 3.04–47.18, p=.025, Cohen’s d=0.57). This change occurred without mean-level or IIV changes in sleep-wake schedules. For all sleep variables except SOL and WAFA, IIV changes and mean-level changes in each variable were negatively correlated (r’s=−.312 to −.691, p’s<.05). Sleep log-derived IIV changes were modestly correlated with mean-level PSQI and PSG-based changes at 12mos. Twelve months of moderate-intensity exercise reduced night-to-night fluctuations in self-rated time to fall asleep, and this relationship was independent of mean-level time to fall asleep.
Intra-individual variability; sleep; physical activity; intervention; unpredictability; sleep-onset latency
To determine the effects of physical resistance strength training and walking (E), individualized social activity (SA), and both E and SA (ESA) compared to a usual care control group on total nocturnal sleep time in nursing home and assisted living residents.
Design, Setting and Participants
The study used a pretest-posttest experimental design with assignment to 1 of 4 groups for 7 weeks: 1) E (n = 55); 2) SA (n = 50); 3) ESA (n = 41); or 4) usual care control (n = 47). 193 residents in 10 nursing homes and 3 assisted living facilities were randomly assigned and 165 completed the study.
The E group participated in high intensity physical resistance strength training 3 days a week and on 2 days walked for up to 45 minutes. The SA group received social activity 1 hour daily 5 days a week. The ESA group received both E and SA, and the control group participated in usual activities provided in the homes.
Total nocturnal sleep time was measured by 2 nights of polysomnography at pre-and post-intervention. Sleep efficiency (SE), non-rapid eye movement (NREM) sleep, rapid eye movement sleep, and sleep onset latency were also analyzed.
Total nocturnal sleep time significantly increased in the ESA group over that of control group (adjusted means 364.2 minutes versus 328.9 minutes), as did SE and NREM sleep.
High intensity physical resistance strength training and walking combined with social activity significantly improves sleep in nursing home and assisted living residents. The interventions by themselves did not have significant effects on sleep in this population.
RCT; sleep; strength training; social activity; walking
To examine the association between sleep-disordered breathing (SDB) and 24-hour blood pressure (BP) pattern among community-dwelling older adults.
A convenience sample of 70 community-dwelling older adults, recruited from senior housing, community centers, and learning centers, were admitted to General Clinical Research Center, Emory University Hospital, Atlanta, Ga. Information regarding demographic and clinical history was obtained using questionnaires. Twenty-four–hour BP monitoring in supine position was performed using Spacelabs model 20207. Breathing during sleep was monitored with the use of a modified sleep recording system (Embletta, PDS), which monitors nasal and oral airflow, chest and abdominal movements, and pulse oximetry. Night time–daytime (night-day) BP ratio (average night-time BP divided by daytime BP) was calculated both for systolic and diastolic BPs.
Sixty-nine participants, mean age 74.9 ± 6.4 years (41 [57%] women), completed the study. The mean apnea-hypopnea index (AHI) was 13 ± 13 per hour of sleep, and 20 participants (29%) had AHI ≥15 per hour of sleep, indicating moderate to severe SDB. Moderate to severe SDB (AHI ≥15 per hour of sleep) was significantly associated with nocturnal hypertension, whereas there was no statistically significant difference in wake-time BP between those with and without moderate to severe SDB. Stepwise multiple regressions showed that AHI independently predicted increased night-day systolic and night-day diastolic BP ratio, even after controlling for nocturia frequency.
The results indicate increased BP load associated with increased AHI in this group of older adults. This increased BP load may contribute to increased hypertension-related morbidity and disease burden.
Sleep-Disordered breathing; 24-hour BP pattern
Although considerable progress has been made in the treatment of chronic kidney disease, compromised quality of life continues to be a significant problem for patients receiving hemodialysis (HD). However, in spite of the high prevalence of sleep complaints and disorders in this population, the relationship between these problems and quality of life remains to be well characterized. Thus, we studied a sample of stable HD patients to explore relationships between quality of life and both subjective and objective measures of nocturnal sleep and daytime sleepiness
The sample included forty-six HD patients, 24 men and 22 women, with a mean age of 51.6 (10.8) years. Subjects underwent one night of polysomnography followed the next morning by a Multiple Sleep Latency Test (MSLT), an objective measure of daytime sleepiness. Subjects also completed: 1) a brief nocturnal sleep questionnaire; 2) the Epworth Sleepiness Scale; and, 3) the Quality of Life Index (QLI, Dialysis Version) which provides an overall QLI score and four subscale scores for Health & Functioning (H&F), Social & Economic (S&E), Psychological & Spiritual (P&S), and Family (F). (The range of scores is 0 to 30 with higher scores indicating better quality of life.)
The mean (standard deviation; SD) of the overall QLI was 22.8 (4.0). The mean (SD) of the four subscales were as follows: H&F – 21.1 (4.7); S&E – 22.0 (4.8); P&S – 24.5 (4.4); and, F – 26.8 (3.5). H&F (rs = -0.326, p = 0.013) and F (rs = -0.248, p = 0.048) subscale scores were negatively correlated with periodic limb movement index but not other polysomnographic measures. The H&F subscale score were positively correlated with nocturnal sleep latency (rs = 0.248, p = 0.048) while the H&F (rs = 0.278, p = 0.030) and total QLI (rs = 0.263, p = 0.038) scores were positively associated with MSLT scores. Both of these latter findings indicate that higher life quality is associated with lower sleepiness levels. ESS scores were unrelated to overall QLI scores or the subscale scores. Subjective reports of difficulty falling asleep and waking up too early were significantly correlated with all four subscale scores and overall QLI. Feeling rested in the morning was positively associated with S&E, P&S, and Total QLI scores.
Selected measures of both poor nocturnal sleep and increased daytime sleepiness are associated with decreased quality of life in HD patients, underscoring the importance of recognizing and treating these patients' sleep problems.