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1.  Daytime REM Sleep in Parkinson’s Disease 
Parkinsonism & related disorders  2012;19(1):101-103.
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.
PMCID: PMC3516626  PMID: 22939103
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.
PMCID: PMC3462821  PMID: 23047598
Electromyography; Sleep; Muscle Activity; Phasic Activity; Polysomnography; Computer Detection
3.  Daytime Alertness in Parkinson’s Disease: Potentially Dose-Dependent, Divergent Effects by Drug Class 
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.
PMCID: PMC3589103  PMID: 22753297
Parkinson’s Disease; Daytime Alertness; Sleep; Maintenance of Wakefulness Test; Dopaminergic Treatment
4.  Periodic Leg Movements in Sleep in Elderly Patients with Parkinsonism and Alzheimer’s Disease 
European Journal of Neurology  2012;19(6):918-923.
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.
PMCID: PMC3351548  PMID: 22340757
Parkinsonism; Alzheimer’s Disease; Periodic Leg Movements in Sleep; Restless Legs Syndrome; Willis-Ekbom Disease
5.  Neurocognitive Correlates of Noctural Oxygen Desaturation in a Memory Clinic Population 
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.
PMCID: PMC3312026  PMID: 22233185
Sleep Apnea; Cardiovascular Disease; Pulse Oximetry; Cognitive Disorders; Geriatrics; Neuropsychology
6.  Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome 
Brain, behavior, and immunity  2012;26(8):1239-1243.
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.
PMCID: PMC3468666  PMID: 22750520
C-reactive protein; periodic leg movements of sleep; restless legs syndrome; interleukin-6; tumor necrosis factor alpha; cardiovascular disease
7.  Nocturnal sleep enhances working memory training in Parkinson's disease but not Lewy body dementia 
Brain  2012;135(9):2789-2797.
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.
PMCID: PMC3577106  PMID: 22907117
consolidation; sleep; working memory; training; Parkinson's disease; dementia with Lewy bodies
8.  Restless Legs Syndrome Risk Factors, Behaviors, and Diagnoses in Persons With Early to Moderate Dementia and Sleep Disturbance 
Behavioral sleep medicine  2010;8(1):48-61.
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.
PMCID: PMC3745281  PMID: 20043249
9.  Incident Sleep Disordered Breathing in Old Age 
Little is known about progression of and risk factors for sleep disordered breathing (SDB) in old age. We prospectively examined elderly volunteers to understand how changes in body weight are related to SDB for a period of 20–30 years.
Participants were 30 surviving members of a community-based cohort (mean entry age = 57.8) studied over a median follow-up of 23.4 years. SDB was quantified as the apnea–hypopnea index (AHI) via in-lab polysomnography from 215 nights, representing 733.3 person-years of follow-up. Weights were recorded in kilograms. We used linear regression to derive individual trajectories of AHI and weight regressed on time.
Individuals had relatively low AHI (X = 2.3 [SD = 3.5]) and body mass index (kg/m2; X = 24.6 [SD = 4.6]) at entry. Rates of change in AHI were characterized by positive slopes and linear increases by least squares regression. Mean rate of change was +0.43 events per hour per year, a 3.3% yearly increase relative to the maximum AHI observed for each case. Within individuals, curve fitting indicated statistically significant AHI increases associated not only with increases, but also decreases, in weight.
Rates of increase in AHI were larger than for aging reported for other organ systems (eg, autonomic, musculoskeletal, and respiratory), possibly reflecting complex mechanistic determination of SDB in old age. Association between decreased weight and increased SDB with advancing years represents an important “proof of concept,” perhaps compatible with failure to maintain airway patency during sleep as a component of generalized muscle weakness in old age.
PMCID: PMC2920579  PMID: 20498222
Sleep disordered breathing; Aging; Body weight; Longitudinal study
10.  No increased risk of obstructive sleep apnea in Parkinson’s disease 
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.
PMCID: PMC3727899  PMID: 20669289
Parkinson’s Disease; Obstructive Sleep Apnea; Excessive Daytime Sleepiness
11.  Phasic Muscle Activity in Sleep and Clinical Features of Parkinson Disease 
Annals of neurology  2010;68(3):353-359.
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.
PMCID: PMC3666956  PMID: 20626046
Sleep medicine clinics  2009;4(1):57-64.
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.
PMCID: PMC2726445  PMID: 20161180
13.  Periodic Leg Movements in Sleep and Restless Legs Syndrome: Considerations in Geriatrics 
Sleep medicine clinics  2006;1(2):263-271.
PMCID: PMC2770895  PMID: 19881897
Periodic leg movement in sleep; restless legs syndrome; nocturnal wandering; anemia; Alzheimer's Disease; Parkinson's Disease
14.  Moderators and Mediators of Exercise-Induced Objective Sleep Improvements in Midlife and Older Adults with Sleep Complaints 
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.
PMCID: PMC3210555  PMID: 21688915
objective sleep; exercise; physical activity; multiple mediation; moderation
15.  Sleep Disturbance in Dementia with Lewy Bodies and Alzheimer's Disease: A Multicenter Analysis 
Evidence suggests that patients with dementia with Lewy bodies (DLB) may have more nocturnal sleep disturbance than patients with Alzheimer's disease (AD). We sought to confirm such observations using a large, prospectively collected, standardized, multicenter-derived database, i.e. the National Alzheimer's Coordinating Center Uniform Data Set.
Nocturnal sleep disturbance (NSD) data, as characterized by the Neuropsychiatric Inventory Questionnaire (NPI-Q), were derived from 4,531 patients collected between September 2005 and November 2008 from 32 National Institute on Aging participating AD centers. Patient and informant characteristics were compared between those with and without NSD by dementia diagnosis (DLB and probable AD). Finally, a logistic regression model was created to quantify the association between NSD status and diagnosis while adjusting for these patient/informant characteristics, as well as center.
NSD was more frequent in clinically diagnosed DLB relative to clinically diagnosed AD (odds ratio = 2.93, 95% confidence interval = 2.22–3.86). These results were independent from the gender of the patient or informant, whether the informant lived with the patient, and other patient characteristics, such as dementia severity, depressive symptoms, and NPI-Q-derived measures of hallucinations, delusions, agitation and apathy. In AD, but not DLB, patients, NSD was associated with more advanced disease. Comorbidity of NSD with hallucinations, agitation and apathy was higher in DLB than in AD. There was also evidence that the percentage of DLB cases with NSD showed wide variation across centers.
As defined by the NPI-Q, endorsement of the nocturnal behavior item by informants is more likely in patients with DLB when compared to AD, even after the adjustment of key patient/informant characteristics.
PMCID: PMC3085031  PMID: 21474933
Dementia with Lewy bodies; Alzheimer's disease; Sleep; Neuropsychiatric Inventory Questionnaire
16.  The effect of nocturia on sleep 
Sleep medicine reviews  2010;15(2):91-97.
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.
PMCID: PMC3137590  PMID: 20965130
nocturia; sleep; insomnia; quality of life
17.  Exercise Effects on Night-to-Night Fluctuations in Self-rated Sleep among Older Adults with Sleep Complaints 
Journal of sleep research  2011;20(1 Pt 1):28-37.
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.
PMCID: PMC2958223  PMID: 20629937
Intra-individual variability; sleep; physical activity; intervention; unpredictability; sleep-onset latency
18.  Strength Training and Walking Exercise and Social Activity Improve Sleep in Nursing Home and Assisted Living Residents: Randomized Controlled Trial 
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.
PMCID: PMC3124380  PMID: 21314643
RCT; sleep; strength training; social activity; walking
19.  Cerebral Oxygenation in Wake and During Sleep and Its Relationship to Cognitive Function in Community-Dwelling Older Adults Without Sleep Disordered Breathing 
This descriptive cross-sectional study investigated the relationships between cerebral oxygen reserve and cognitive function in community-dwelling older adults.
Participants (72 women and 40 men) underwent standard polysomnography, including regional measures of percent oxyhemoglobin saturation (rcSO2) determined by cerebral oximetry. Two variables were used to calculate cerebral oxygen reserve: (a) awake rcSO2 (mean presleep rcSO2) and (b) the change in rcSO2 from before sleep to the end of the first non-rapid-eye movement cycle. General linear models, adjusted for the effects of education and occupation, tested differences in performance on standard tests of memory, attention, and speed of mental processing.
Awake rcSO2 values were normal (60%–79.9%) in 64 participants, marginal (50%–59.9%) in 41, and low (43%–49.9%) in 7. Participants with normal awake levels had higher cognitive function than those with low levels (p < .05). Changes in rcSO2 were greatest in participants with marginal awake rcSO2 values; among whom, those who increased rcSO2 during sleep (n = 17) had better memory function than the 24 who did not (p < .05).
Low awake rcSO2 values mark individuals with low cerebral oxygen reserves and generally lower cognitive function; marginal awake rcSO2 values that fall during sleep may indicate loss of cerebral oxygen reserve and an increased risk for cognitive decline. Further studies may clarify the significance of and mechanisms underlying individual differences in awake rcSO2 and the changes that occur in rcSO2 while asleep.
PMCID: PMC3011955  PMID: 21076087
Cerebral oxygenation; Sleep; Cognition
20.  Wake promoting effects of cocaine-and amphetamine-regulated transcript (CART) 
Neuropeptides  2010;44(3):241-246.
Cocaine- and amphetamine-regulated transcript (CART) peptides modulate anxiety, food intake, endocrine function, and mesolimbic dopamine related reward and reinforcement. Each of these disparate behaviors takes place during the state of wakefulness. Here, we identify a potential wake promoting role of CART by characterizing its effects upon sleep/wake architecture in rats. Dose-dependent increases in wake were documented following intracerebroventricular CART 55–102 administered at the beginning of the rat’s major sleep period. Sustained wake was observed for up to 4 hours following delivery of 2.0 μg of CART peptide. The wake promoting effect was specific to active CART 55–102 because no effect on sleep/wake was observed with the inactive form of the peptide. Increased wake was followed by robust rebound in NREM and REM sleep that extended well into the subsequent lights-off, or typical wake period, of the rat. These findings point to a potential novel role for CART in regulating wakefulness.
PMCID: PMC2854259  PMID: 20116848
hypothalamus; rebound; hypocretin; sleep
21.  Sleep-disordered Breathing and Frailty in the Cardiovascular Health Study Cohort 
American Journal of Epidemiology  2009;170(2):193-202.
Sleep-disordered breathing (SDB) is associated with pathophysiology that may influence the development and progression of frailty. Using data collected in 1995–1996, the authors explored the relation between SDB and components of frailty among 1,042 participants of the Cardiovascular Health Study. Diagnosis of SDB was based on the results of overnight polysomnography, and severe SDB was defined as an apnea-hypopnea index of >30 per hour of sleep. Slow walking speed, low grip strength, exhaustion, low physical activity, and unexplained weight loss were referred to as frailty indicator variables. There were 584 (56%) female and 458 (44%) male participants, and the mean age was 77 (standard deviation, 4) years. There was independent association between severe SDB and 1 or more frailty indicator variables (adjusted odds ratio = 4.85, 95% confidence interval: 1.40, 16.78), slow walking speed (adjusted odds ratio = 2.67, 95% confidence interval: 1.04, 6.84), and low grip strength (adjusted odds ratio = 3.29, 95% confidence interval: 1.36, 7.96) among female study participants. The finding of an independent association between SDB and frailty indicator variables among older women could have important implications in interventions aimed at preventing or delaying the progression of frailty.
PMCID: PMC2727272  PMID: 19465743
frailty; hand strength; mobility limitation; muscle strength; sleep apnea syndromes; weight loss
Sleep medicine  2008;10(5):540-548.
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.
PMCID: PMC2735085  PMID: 18703381
Aging; Health Survey; Nocturia; Sleep Initiation and Maintenance Disorders; Prostatism; Falls
23.  Sleep-Disordered Breathing and 24-Hour Blood Pressure Pattern Among Older Adults 
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.
PMCID: PMC2655030  PMID: 19196901
Sleep-Disordered breathing; 24-hour BP pattern
24.  Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis 
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.
PMCID: PMC320494  PMID: 14633280
25.  Phasic Electromyographic Metric detection based on wavelet analysis 
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.
PMCID: PMC3873000  PMID: 24385139

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