Restless Legs Symptoms and Periodic Leg Movements in Sleep Among Patients with Parkinson's Disease.

BACKGROUND: The association between restless legs syndrome (RLS) and Parkinson's disease (PD) remains controversial, with epidemiologic and descriptive evidence suggesting some potential overlap while mechanistic/genetic studies suggesting relative independence of the conditions. OBJECTIVE: To examine a known, objectively measured endophenotype for RLS, periodic leg movements (PLMS) in sleep, in patients with PD and relate that objective finding to restless legs symptoms. METHODS: We performed polysomnography for one (n = 8) or two (n = 67) consecutive nights in 75 PD patients and examined the association of PLMS with restless legs symptoms. RESULTS: We found no association between restless legs symptoms and PLMS in PD. Prevalence of both was similar to data reported previously in other PD samples. CONCLUSION: We interpret these results as suggesting that restless legs symptoms in PD patients may represent a different phenomenon and pathophysiology than RLS in the non-PD population.

Habitual and Recent Sleep Durations: Graded and Interactive Risk for Impaired Glycemic Control in a Biracial Population.

BACKGROUND: We examined how habitual sleep duration interacts with recent sleep (2 nights) to predict morning oral glucose tolerance test results. We hypothesized that short habitual and recent sleep durations would be additive for poor glucose control. METHODS: A biracial population of adults (n = 1559) without known diabetes and recruited from the workforce of 2 urban universities was assessed for glycated hemoglobin and underwent oral glucose tolerance testing. We used plasma 2-hour postloading (75 g) measurements. Participants answered sleep questions using 30-minute forced-choice formats. We employed multivariable logistic regression to derive odds ratios. RESULTS: Shorter habitual sleep duration was associated with greater odds ratios of glycated hemoglobin ≥6.0% increasing by 30-minute intervals beginning at <7.0 hours and were more pronounced as durations shortened. Among participants with glycated hemoglobin <6.0% and <7.0 hours of habitual sleep (n = 636), abnormal glucose tolerance (2-hour oral glucose tolerance test ≥140 mg/dL) was significantly associated with a total sleep duration of ≤11 hours the 2 nights preceding oral glucose tolerance testing, but was not associated with longer sleep durations. Results were independent of age, sex, race, body mass index, smoking, history of cardiovascular disease, or use of antihypertensive or cholesterol-lowering medication. Additional analyses implied that longer-than-usual recent sleep durations were protective for abnormal oral glucose tolerance testing. DISCUSSION: Short habitual and recent sleep durations interact in predicting abnormal glucose on oral glucose tolerance testing. Self-reported data are sufficiently sensitive to reflect 30-minute differences in sleep between individuals. Future studies examining other aspects of sleep, such as perceived sleep quality and objectively measured sleep duration and architecture, would be necessary to confirm these findings. CONCLUSIONS: Short sleep duration for 2 nights prior to morning oral glucose tolerance testing may elevate glucose levels, this effect being detected among individuals habitually obtaining <7 hours sleep and obtaining ≤11 hours of sleep for 2 nights preceding testing.

Nocturnal sleep enhances working memory training in Parkinson's disease but not Lewy body dementia.

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.

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 antiparkinsonian 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, first, 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. Second, the results showed that 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 the Maintenance of Wakefulness Test defined daytime alertness including 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 used. 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.

Sleep disturbance in dementia with Lewy bodies and Alzheimer's disease: a multicenter analysis.

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Phasic muscle activity in sleep and clinical features of Parkinson disease.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

Correlates of PLMs variability over multiple nights and impact upon RLS diagnosis.

OBJECTIVE: Night-to-night variability of periodic leg movements (PLMs) in restless legs syndrome (RLS) was examined to define the range of intra-subject values, impact upon diagnosing RLS, and clinical correlates. METHODS: Twenty RLS patients were monitored for 10-15 nights using a validated, tri-axial accelerometer worn on the ankle. RESULTS: The mean difference in PLMs index (PLMI) between the lowest and highest night was 25.1/h (range: 3.9-73.8). Inter-subject differences accounted for nearly five times the variance in PLMI relative to between nights within an individual. Based on a single night of recording, PLMI criterion thresholds of 5, 10, and 15/h were exceeded on approximately 70.1%, 51.9% and 34.1% of individual nights among these patients. Based on five randomly sampled nights of recordings, the likelihood that such thresholds were met on at least a single night increased to 91.2%, 80.8% and 62.7%, respectively. Women exhibited greater variability. CONCLUSIONS: Variability in PLMs within RLS subjects was substantial, yet individuals' characteristic PLM level represented a quantitative trait. Variability was unrelated to age or scores on scales of RLS severity, sleepiness, functional status, and mood. A larger number of recording nights increased the likelihood that any criterion was reached.

Effect of supine knee position on obstructive sleep apnea.

We previously reported a case of a middle-aged man whose obstructive sleep apnea (OSA) was virtually eliminated when he slept in the supine "knees up" position. In this study, we attempt to replicate this phenomenon in a group of volunteers with previously diagnosed OSA. Results indicated no significant improvement in OSA when sleeping supine knees up. Examination of distribution of within subjects' change [calculated as Respiratory Disturbance Index (RDI) in the "knees down" position vs RDI in the knees up position] indicated a trend for improvement in the latter (p=0.12, two-tailed probability). These results suggest that knee position is unlikely to be a robust intervention for OSA though they allow for the possibility that some patients may have a moderation of their condition by such a manipulation.