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Sleep disorders are among the most common non-motor manifestations in Parkinson's disease (PD) and have a significant negative impact on quality of life. While sleep disorders in PD share most characteristics with those that occur in the general population, there are several considerations specific to this patient population regarding diagnosis, management, and implications. The available research on these disorders is expanding rapidly, but many questions remain unanswered. We thus conducted a systematic review of the literature published from 2005 to 2015 on the following disorders of sleep and wakefulness in PD: REM sleep behavior disorder, insomnia, nocturia, restless legs syndrome and periodic limb movements, sleep disordered breathing, excessive daytime sleepiness, and circadian rhythm disorders. We discuss the epidemiology, etiology, clinical implications, associated features, evaluation measures, and management of these disorders. The influence on sleep of medications used in the treatment of motor and non-motor symptoms of PD is detailed. Additionally, we suggest areas in need of further research. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Over 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity. Methods: In a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics. Results: Among 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities. Conclusion: Surface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury. [Copyright &y& Elsevier]

Abstract: Background: Poor nocturnal sleep is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopaminergic drugs influence nocturnal sleep in PD, particularly in relation to medication timing. We examined the association between dopaminergic medications and subjective and objective nocturnal sleep in PD. Methods: Individuals with PD were recruited from the outpatient clinic. Demographics and disease information were collected. Patients underwent one-night polysomnography and responded to SCOPA-SLEEP, a self-administered questionnaire which includes a section on nighttime sleep and an overall measure of sleep quality; higher scores indicate worse sleep. Medication intake, including medication timing in relation to bedtime, was obtained and converted to levodopa equivalents. Results: 41 Males and 21 females, median age 63.9 years, participated. Median disease duration was 5 years. After adjusting for age, sex, disease severity, and disease duration, greater total levodopa equivalent intake within 4 h of sleep was associated with higher total SCOPA-nighttime score (p = 0.009) and greater wake time after sleep onset (p = 0.049). Greater dopaminergic medication intake prior to sleep was also associated with less rapid eye movement (REM) sleep as a percent of total sleep time (p = 0.004). Conclusions: Higher amounts of dopaminergic medications taken prior to sleep were associated with poor sleep quality and less REM sleep. Although poor nocturnal sleep in PD is likely multi-factorial in etiology, our findings suggest that timing and dose of medications prior to sleep need to be considered in its management. [Copyright &y& Elsevier]

Background: TH2 cytokines play crucial roles in driving human B lymphocytes to produce IgE. However, it is unclear whether IL-4 and IL-13 have parallel or sequential roles in the development of B lymphocytes. Objective: We investigated IL-13 receptor (IL-13R) expression and regulation in mature and immature human B cells. Methods: Purified B cells were isolated from human tonsils. We evaluated IL-13Rα1 mRNA expression using real-time PCR and IL-13Rα1 and IL-4 receptor (IL-4R) α expression using flow cytometry and microscopy. Signal transduction was assessed on the basis of signal transducer and activator of transcription 6 phosphorylation. Results: IL13Rα1 mRNA was induced after stimulation with anti-CD40 antibodies, anti-CD40 plus IL-4, or anti-IgM/IgG. Baseline surface IL13Rα1 levels were low in unstimulated B cells but increased significantly at 24 hours and were sustained for 5 to 14 days. In contrast, IL4Rα was constitutively expressed on tonsillar B cells, and levels did not significantly vary after stimulation. B cells activated by CD40 ligation or B-cell receptor cross-linking, but not resting B cells, showed significant increases in signal transducer and activator of transcription 6 phosphorylation in response to IL-13. IL-13Rα1 expression was induced on mature and memory B cells, as well as on naive subsets. Conclusions: There is lower constitutive expression and signaling of IL13Rα1 in resting tonsillar B lymphocytes compared with that of IL4Rα. IL-13 is induced on both immature and mature B lymphocytes. Clinical implications: This implies different roles for IL-4 and IL-13 in B-cell development, which would allow for specific targeting of IL-13 in IgE-mediated diseases. [Copyright &y& Elsevier]

Abstract: Older individuals are given low priority compared to other age groups in many societies and geriatric care is not well-developed in many countries. With the global trend in population aging, the increasing number of older adults can be expected to challenge already-fragile health care facilities. Health care systems vary greatly from one country to another. Based on common research interests and through an educational exchange program between the University of Groningen (the Netherlands) and the American University of Beirut (Lebanon), a project was started to compare the Dutch and Lebanese health care delivery systems for older individuals, demonstrate their strengths and pitfalls, and draw from their resemblance and differences pivotal conclusions leading to positive change. In particular we examined the nursing homes, geriatric medicine and insurance coverage, and pension plans of both countries. [Copyright &y& Elsevier]

Background: IL-9 has been shown to affect the differentiation pathway of different cell types. However, its potential role in the maturation pathway of antigen-driven B-cell differentiation and its functional effects remain unknown. Objective: To characterize IL-9 receptor α chain (IL-9Rα) expression on human tonsillar B cells at different maturational stages, and to assess its effect on IgE production. Methods: Freshly purified human tonsillar B cells were fractionated into 3 populations: low-density (LD), medium-density, and high-density cells. Expression levels of IL-9Rα were determined by using immunohistochemistry and flow cytometry. IL-9Rαhigh–expressing cells were stimulated with IL-9 in the presence or absence of IL-4, and IgE release was measured by ELISA. Results: IL-9Rα was expressed on human LD tonsillar B cells, with an ability to transduce signals through activation of signal transducer and activator of transcription 3 and 5. Although IL-9 was unable to induce IgE secretion by itself, it potentiated IL-4–mediated IgE production from LD cells. Moreover, increased IgE was paralleled by an upregulation of IL-9Rα and CD27, with the latter a memory B-cell marker implicated in increased IgE secretion. Conclusion: These results highlight a crucial role for IL-9 in modulating T-cell–dependent B-cell differentiation and establish a new paradigm for understanding the synergistic role of TH2 cytokines and their modulatory effect on B-cell maturation and IgE production. Clinical implications: IL-9 appears to be involved in memory B-cell differentiation and TH2-mediated allergic diseases such as asthma. [Copyright &y& Elsevier]

Summary: There is a pressing need for biomarkers to diagnose Parkinson's disease (PD), assess disease severity, and prognosticate course. Various types of biologic specimens are potential candidates for identifying biomarkers – defined here as surrogate indicators of physiological or pathophysiological states – but blood has the advantage of being minimally invasive to obtain. There are, however, several challenges to identifying biomarkers in blood. Several candidate biomarkers identified in other diseases or in other types of biological fluids are being pursued as blood-based biomarkers in PD. In addition, unbiased discovery is underway using techniques including metabolomics, proteomics, and gene expression profiling. In this review, we summarize these techniques and discuss the challenges and successes of blood-based biomarker discovery in PD. Blood-based biomarkers that are discussed include α-synuclein, DJ-1, uric acid, epidermal growth factor, apolipoprotein-A1, and peripheral inflammatory markers. [Copyright &y& Elsevier]

Objective: To evaluate the association between baseline olfaction and both cross-sectional and longitudinal cognitive assessments, motor symptoms, non-motor symptoms (NMS), and CSF biomarkers in early Parkinson's disease (PD).Methods: Parkinson's Progression Marker's Initiative (PPMI) participants underwent baseline olfactory testing with the University of Pennsylvania Smell Identification Test (UPSIT). Serial assessments included measures of motor symptoms, NMS, neuropsychological assessment, and CSF biomarkers. Up to three years follow-up data were included.Results: At baseline, worse olfaction (lowest tertile) was associated with more severe NMS, including anxiety and autonomic symptoms. Those in the lowest olfactory tertile were more likely to report cognitive impairment (37.4%) compared to those in the middle (24.4%) and highest olfactory tertiles (14.2%, p < 0.001). Aβ1-42 was significantly lower, and tau/Aβ1-42 ratio was higher in those with worse olfaction. In longitudinal analyses, lower UPSIT score was associated with greater decline in MoCA score (β = 0.02 [0.01, 0.03], p = 0.001) over time, as were composite measures of UPSIT score and either Aβ1-42 or tau/Aβ1-42 ratio. In a Cox proportional hazards model, a composite measure of olfaction and Aβ1-42 was a significant predictor of conversion from normal cognition to mild cognitive impairment (MCI; i.e., MoCA < 26), with subjects most impaired on both measures being 87% more likely to develop incident MCI (HR = 1.87 [1.16, 3.01], p = 0.01).Conclusions: Worse baseline olfaction is associated with long-term cognitive decline. The addition of AD CSF biomarkers to olfactory testing may increase the likelihood of identifying those at highest risk for cognitive decline and progression to MCI. [ABSTRACT FROM AUTHOR]

Abstract: Adequate and balanced nutrition during gestation is essential for achieving healthy pregnancy outcomes. This retrospective survey tested the hypothesis that maternal nutrition (macronutrients intake, micronutrients intake, and weight gain) during gestation will impact gestational outcomes (gestational age, birth weight, and labor spontaneity). The objectives of this study were to test the impact of macronutrients and micronutrients consumed during gestation, pregestational weight and weight gain during gestation on gestational age, birth weight, and labor spontaneity among Jordanian women. Study participants (n = 700) were recruited from a women''s hospital in northern Jordan. Data were collected using structured interviews. Dietary determinants examined in the study included daily intake of macronutrients (energy, carbohydrate, protein, fat, and n-3 and n-6 fatty acids) and micronutrients (zinc, calcium, folate, vitamin C, vitamin A, and vitamin B6), pregestational body mass index, total weight gain, and weight gain pattern during pregnancy. Dietary data were obtained from a semiquantitative food frequency questionnaire. Mean (SEM) daily intakes of energy, carbohydrate, and protein were 10894 (138) Kj, 320 (3.8) g, and 90 (0.95) g, respectively; with fat contributing 36% of total energy. Average daily energy and carbohydrate intake during pregnancy were related negatively to gestational age (P < .05). Pregestational body mass index was associated positively with gestational age and birth weight (P < .05). Intakes of vitamin A and calcium had significant relationships with birth weight. Daily intakes of zinc, calcium, vitamin B6, and n-3 and n-6 fatty acids were associated with labor spontaneity. Dietary factors consumed during pregnancy are associated with pregnancy outcomes. [Copyright &y& Elsevier]