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1.  A Neurodegenerative Disease Sleep Questionnaire: Principal Components Analysis in Parkinson’s Disease 
Sleep disturbances are common in many neurodegenerative diseases and may include altered sleep duration, fragmented sleep, nocturia, excessive daytime sleepiness, and vivid dreaming experiences, with occasional parasomnias. Although representing the “gold standard,” polysomnography is not always cost-effective or available for measuring sleep disturbance, particularly for screening. Although numerous sleep-related questionnaires exist, many focus on a specific sleep disturbance (e.g., restless legs, REM Behavior Disorder) and do not capture efficiently the variety of sleep issues experienced by such patients. We developed and administered the 12-item Neurodegenerative Disease Sleep Questionnaire (NDSQ) and the Epworth Sleepiness Scale to 145 idiopathic Parkinson’s disease patients. Principal component analysis using eigenvalues greater than 1 suggested five separate components: sleep quality (e.g., sleep fragmentation), nocturia, vivid dreams/nightmares, restless legs symptoms, and sleep-disordered breathing. These results demonstrate construct validity of our sleep questionnaire and suggest the NDSQ may be a useful screening tool for sleep disturbances in at least some types of neurodegenerative disorders.
PMCID: PMC3947083  PMID: 24074551
sleep questionnaire; principal components analysis; nocturia; sleep disordered breathing; dreaming; restless legs syndrome; neurodegenerative disease; Parkinson’s disease
2.  Fluctuations in Cognition and Alertness Vary Independently in Dementia with Lewy Bodies 
Fluctuations in mental status are one of the core diagnostic criteria for Dementia with Lewy Bodies (DLB) and are thought to reflect variability in daytime alertness. Previous attempts to study fluctuations have been limited to caregiver reports, observer rating scales, short segments of electroencephalography, or motor-dependent, reaction time tests. Concordance among such measures is often poor, and fluctuations remain difficult to quantify.
We compared fluctuations in cognition and alertness in patients with DLB (n = 13) and idiopathic Parkinson’s Disease (n = 64), a condition associated with deficits in daytime alertness. We systematically and repeatedly collected cognitive and physiologic measures during a 48-hour inpatient protocol in a sound-attenuated sleep laboratory in a geriatric hospital. Cognitive fluctuations were analyzed using coefficients of variation (COVs) derived from performance on a bedside examination familiar to clinicians (digit span). Alertness fluctuations were assessed objectively using COVs from the polysomnographically-based Maintenance of Wakefulness Test.
Despite predictably lower mean digit span performances, DLB patients demonstrated significantly greater cognitive fluctuations than PD patients (p <.001), even when groups were matched on general cognitive impairment. There were no group differences in alertness fluctuations, although DLB patients were less alert than PD patients not receiving dopaminergics.
The prevailing assumption that fluctuations in cognition in DLB are reflected in fluctuations in daytime alertness was not supported by objective, physiological measurements. Fluctuating mental status in DLB patients can be detected with repeated administration of a simple bedside exam that can be adapted to a clinic setting.
PMCID: PMC3946909  PMID: 24151106
Dementia with Lewy Bodies; fluctuations; cognition; alertness; digit span
3.  Invited Commentary: Alzheimer’s Disease, Sleep Apnea, and Positive Pressure Therapy 
PMCID: PMC3909520  PMID: 24198176
Alzheimer’s disease; Sleep apnea; Positive pressure therapy; Impaired cognition; Clinical trials
4.  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
6.  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
7.  Sleep-related problems and urologic symptoms: Testing the hypothesis of bi-directionality in a longitudinal, population-based study 
The Journal of urology  2013;191(1):10.1016/j.juro.2013.07.011.
To evaluate the bi-directional association between urologic symptoms (urinary incontinence (UI), lower urinary tract symptoms (LUTS), and nocturia) and sleep-related variables.
Materials and Methods
Data were obtained from a prospective cohort study of 1,610 men and 2,535 women who completed baseline (2002–05) and follow-up (2006–10) phases of the Boston Area Community Health (BACH) survey, a population-based random sample survey. Sleep restriction (≤5 hours/night), restless sleep, sleep medication use, and urologic symptoms were assessed by self-report. UI was defined as weekly leakage or moderate/severe leakage, LUTS (overall, obstructive, irritative) was defined by American Urological Association Symptom Index, and nocturia was defined as urinary frequency ≥2 times/night.
At the 5 year follow-up,10.0%, 8.5% and 16.0% of subjects newly reported LUTS, UI and nocturia, respectively, and 24.2%, 13.3%, 11.6% newly reported poor sleep quality, sleep restriction and use of sleep medication, respectively. Controlling for confounders, the odds of developing urologic symptoms was consistently increased for subjects who reported poor sleep quality and sleep restriction at baseline, but only baseline nocturia was positively associated with incident sleep-related problems at follow-up. Body mass index, a potential mediator, reduced selected associations between sleep and incident UI and irritative symptoms, but C-reactive protein did not.
These data suggest that self-reported sleep-related problems and urologic symptoms are linked bi-directionally, and BMI may be a factor in the relationship between sleep and development of urologic symptoms.
PMCID: PMC3865224  PMID: 23867307
Cohort Studies; Epidemiology; Sleep; Urologic Diseases
8.  Treatment of the Sleep Disorders Associated with Parkinson’s Disease 
Neurotherapeutics  2013;11(1):68-77.
Sleep disorders are common in patients with Parkinson’s disease (PD), and preliminary work has suggested viable treatment options for many of these disorders. For rapid eye movement sleep behavior disorder, melatonin and clonazepam are most commonly used, while rivastigmine might be a useful option in patients whose behaviors are refractory to the former. Optimal treatments for insomnia in PD have yet to be determined, but preliminary evidence suggests that cognitive–behavioral therapy, light therapy, eszopiclone, donepezil, and melatonin might be beneficial. Use of the wake-promoting agent modafinil results in significant improvement in subjective measures of excessive daytime sleepiness, but not of fatigue. Optimal treatment of restless legs syndrome and obstructive sleep apnea in PD are not yet established, although a trial of continuous positive airway pressure for sleep apnea was recently completed in PD patients. In those patients with early morning motor dysfunction and disrupted sleep, the rotigotine patch provides significant benefit.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-013-0236-z) contains supplementary material, which is available to authorized users.
PMCID: PMC3899483  PMID: 24272458
REM sleep behavior disorder; Insomnia; Excessive daytime sleepiness; Fatigue; Restless legs syndrome; Obstructive sleep apnea
9.  Geographic variations in sleep duration: a multilevel analysis from the Boston Area Community Health (BACH) Survey 
Sleep plays an important role in health and varies by social determinants. Little is known, however, about geographic variations in sleep and the role of individual-level and neighbourhood-level factors.
We used a multilevel modelling approach to quantify neighbourhood variation in self-reported sleep duration (very short <5 h; short 5–6.9 h; normative 7–8.9 h; long ≥9 h) among 3591 participants of the Boston Area Community Health Survey. We determined whether geographic variations persisted with control for individual-level demographic, socioeconomic status (SES) and lifestyle factors. We then determined the role of neighbourhood SES (nSES) in geographic variations. Additional models considered individual health factors.
Between neighbourhood differences accounted for a substantial portion of total variability in sleep duration. Neighbourhood variation persisted with control for demographics, SES and lifestyle factors. These characteristics accounted for a portion (6–20%) of between-neighbourhood variance in very short, short and long sleep, while nSES accounted for the majority of the remaining between-neighbourhood variances. Low and medium nSES were associated with very short and short sleep (eg, very short sleep OR=2.08; 95% CI 1.38 to 3.14 for low vs high nSES), but not long sleep. Further inclusion of health factors did not appreciably increase the amount of between-neighbourhood variance explained nor did it alter associations.
Sleep duration varied by neighbourhood in a diverse urban setting in the northeastern USA. Individual-level demographics, SES and lifestyle factors explained some geographic variability, while nSES explained a substantial amount. Mechanisms associated with nSES should be examined in future studies to help understand and reduce geographic variations in sleep.
PMCID: PMC4267956  PMID: 25199880
10.  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
11.  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
12.  Sleep and Impulsivity in Parkinson’s Disease 
Parkinsonism & related disorders  2013;19(11):10.1016/j.parkreldis.2013.06.018.
Impulsive behavior and poor sleep are important non-motor features of Parkinson’s disease (PD) that negatively impact the quality of life of patients and their families. Previous research suggests a higher level of sleep complaints in PD patients who demonstrate impulsive behaviors, but the nature of the sleep disturbances has yet to be comprehensively tested.
Consecutive idiopathic PD patients (N=143) completed the Minnesota Impulse Disorder Interview and a sleep questionnaire that assessed sleep efficiency, excessive daytime sleepiness, restless legs symptoms, snoring, dreams/nightmares, and nocturia. Patients were also given a Unified Parkinson’s Disease Rating Scale motor examination and they completed cognitive testing.
Impulsive PD patients endorsed more sleep complaints than non-impulsive PD patients. The group difference was primarily attributable to poor sleep efficiency (e.g., greater nocturnal awakenings), p < .01, and greater daytime sleepiness, p < .01, in the impulsive PD patients. Interestingly, restless legs symptoms were also greater in the impulsive PD patients, p < .05. The results could not be explained by medications or disease severity.
Poor sleep efficiency, restless legs symptoms, and increased daytime sleepiness are associated with impulsivity in PD. Longitudinal studies are needed to determine whether sleep disturbances precede impulsivity in PD.
PMCID: PMC3878049  PMID: 23880026
Parkinson s disease; sleep; impulse control disorder; excessive daytime sleepiness
13.  Nocturia and Overnight Polysomnography in Parkinson Disease 
Neurourology and urodynamics  2013;32(8):10.1002/nau.22365.
Characterize clinical factors related to nocturia and sleep disruption in PD using polysomnography (PSG).
Sixty-three PD patients were recruited regardless of sleep or voiding complaints from a university-based movement disorders clinic for a 48-hour inpatient PSG protocol. Nocturia frequency and bother related to urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) and were corroborated by measurements of PSG-defined sleep made immediately preceding and subsequent to each in-lab voiding episode. PSG measures included whole-night total sleep time (TST), sleep efficiency (SE), Apnea/Hypopnea Index (AHI), and time to PSG-defined sleep following nocturia episodes. Differences between groups were assessed using Mantel-Haenszel chi-square, t-tests, or Wilcoxon signed rank tests. Linear regression was used to assess factors associated with reported nocturia frequency.
Sixty patients completed the IPSS. Thirty-seven (61%) reported at least 2 nocturia episodes nightly; those individuals demonstrated lower PSG-defined SE (p =.01) and TST (p =.02) than patients with 0-1 episodes. Participants reporting 2-3 episodes of nocturia with high bother on the IPSS (n=12) demonstrated lower whole-night TST (280.5 ± 116.1 min vs. 372.5 ± 58.7 min, p=0.03) and worse SE (59.2% ± 22.7 vs. 75.9% ± 11.2, p=0.04) when compared to participants with 2-3 episodes of nocturia with low bother (n=13).
These results verify objectively that PD patients with nocturia have poor sleep. Furthermore, among individuals with comparable levels of reported nocturia, higher bother is associated with poorer sleep as defined on PSG.
PMCID: PMC3808459  PMID: 23359220
nocturia; bother; polysomnography; sleep efficiency; Parkinson disease
14.  Racial and socioeconomic disparities in sleep and chronic disease: results of a longitudinal investigation 
Ethnicity & disease  2013;23(4):499-507.
Sleep problems appear to differentially affect racial minorities and people of lower socioeconomic status (SES). These population subgroups also have higher rates of many debilitating diseases such as obesity, type 2 diabetes mellitus (T2DM), hypertension, coronary heart disease, stroke, and mortality. Considering the presence of social disparities in sleep and chronic disease, this research aims to assess the role of sleep disparities in the incidence of obesity, T2DM, hypertension, and/or cardiovascular disease (CVD).
The Boston Area Community Health (BACH) Survey is a population-based random-sample cohort of 5502 participants aged 30-79. Sleep restriction (≤5 hours/night) and restless sleep were assessed at baseline. Health status was ascertained at baseline and approximately 5 years later among 1610 men and 2535 women who completed follow-up.
Subjects completed an in-person, home visit, interview at baseline (2002- 2005) and follow-up (2006-2010).
Boston, Massachusetts residents (2301 men, 3201 women) aged 30-79 years from three racial groups (1767 Black, 1876 Hispanic, 1859 White) participated in the BACH Survey.
There were significant differences in the prevalence of sleep-related problems at baseline by both race and SES as well as significant disparities in the incidence of T2DM, high blood pressure and cardiovascular disease at follow-up. Restless sleep was associated with an increased risk of obesity, T2DM, and CVD. However, we found that sleep does not mediate social disparities in health outcomes.
Results from the BACH Survey confirm large social disparities in health outcomes as well as large social disparities in short sleep duration and restless sleep. However, sleep did not appear to mediate the relationship between race, SES, and health disparities.
PMCID: PMC3884220  PMID: 24392615
disparities; sleep quality; chronic disease
15.  A prospective photographic study of the ocular fundus in obstructive sleep apnea 
The prevalence of optic nerve and retinal vascular changes within the obstructive sleep apnea (OSA) population are not well known, although it has been postulated that optic nerve ischemic changes and findings related to elevated intracranial pressure may be more common in OSA patients. We prospectively evaluated the ocular fundus in unselected patients undergoing overnight diagnostic polysomnography (PSG).
Demographic data, past medical/ocular history and non-mydriatic fundus photographs were prospectively collected in patients undergoing polysomnography at our institution and reviewed for the presence of optic disc edema for which our study was appropriately powered a priori. Retinal vascular changes were also evaluated. OSA was defined using measures of both sleep disordered breathing and hypoxia.
Of 250 patients evaluated in the sleep center, fundus photographs were performed on 215 patients, among whom 127 patients (59%) had an apnea/hypopnea index (AHI) ≥15 events per hour, including 36 with severe OSA. Those with AHI<15 served as the comparison group. None of the patients had optic disc edema (95%CI:0-3%). There was no difference in rates of glaucomatous appearance or pallor of the optic disc among the groups. Retinal arteriolar changes were more common in severe OSA patients (OR: 1.09 per 5 unit increase in AHI, 95%CI: 1.02-1.16; p=0.01), even after controlling for mean arterial blood pressure.
We did not find an increased prevalence of optic disc edema or other optic neuropathies in our OSA population. However, retinal vascular changes were more common in patients with severe OSA, independent of blood pressure.
PMCID: PMC3750087  PMID: 23736744
sleep apnea; optic nerve; retina; neuro-ophthalmology
16.  Neuropsychiatric symptoms in Alzheimer’s disease: Past progress and anticipation of the future 
Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer’s first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer’s Association convened a Research Roundtable on the topic of NPS in AD. A major outcome of the Roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer’s Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome specific synthetic reviews and recommendations prepared by NPS-PIA Workgroups on depression, apathy, sleep, agitation, and psychosis.
PMCID: PMC3766403  PMID: 23562430
Neuropsychiatric symptoms; Behavioral and psychological symptoms of dementia; Agitation/aggression; Sleep disorders; Depression; Apathy; Psychosis; Delusions; Hallucinations; Dementia; Alzheimer’s disease; Mild cognitive impairment; Mild Behavioral Impairment
17.  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
18.  Obstructive sleep apnea in idiopathic intracranial hypertension: comparison with matched population data 
Journal of neurology  2013;260(7):1748-1751.
Patients with idiopathic intracranial hypertension (IIH) frequently have coexisting obstructive sleep apnea (OSA). We aimed to determine if the prevalence and severity of OSA is greater in patients with IIH than would be expected given their other risk factors for OSA. We included 24 patients (20 women, 4 men) with newly-diagnosed IIH who had undergone overnight polysomnography. We calculated the expected apnea-hypopnea index (AHI) for each patient, based on their age, sex, race, body mass index (BMI), and menopausal status, using a model derived from 1741 randomly-sampled members of the general population who had undergone overnight polysomnography. We compared the AHI values obtained from polysomnography with those predicted by the model using a paired t-test. Our study had 80% power to detect a 10 unit change in mean AHI at α=0.05. Eight patients (33.3%; 6 women, 2 men) had OSA by polysomnography. AHIs from polysomnography were not significantly different from those predicted by the model (mean difference 3.5, 95% CI: −3.0–9.9, p=0.28). We conclude that the prevalence and severity of OSA in IIH patients is no greater than would be expected for their age, sex, race, BMI, and menopausal status. It remains unclear if the presence or treatment of OSA influences the clinical course of IIH.
PMCID: PMC3707935  PMID: 23412355
Idiopathic intracranial hypertension; Papilledema; Obstructive sleep apnea; Intracranial pressure
19.  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
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
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
22.  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
23.  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
24.  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
25.  Sleep Disturbance in Women Prior to Myocardial Infarction 
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.
PMCID: PMC3432660  PMID: 22770599
cardiovascular disease; cognitive disorders; sleep disturbance; menopause; women

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