Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

BackgroundThere is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied.ObjectiveTo investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations.MethodsCross-sectional study. Patients with PD (n = 148); age 65.6 ± 7.4 years, Hoehn and Yahr stage 2.4 ± 0.6, with (n = 15) and without (n = 133) comorbid type II DM, underwent [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates.ResultsThere were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98 ± 1.01) compared to the non-diabetics (−0.36 ± 0.91; F = 7.78, P = 0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F = 8.39, P < 0.0001).ConclusionDiabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.     

Characterizing the Mechanisms of Central and Peripheral Forms of Neurostimulation in Chronic Dysphagic Stroke Patients

BackgroundSwallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration.Objective/hypothesisOur hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response.MethodsIn 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy.ResultsCorticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F_1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = −2.79) was observed compared to sham.ConclusionsIn this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = −.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.     

Non-invasive Vagus Nerve Stimulation in Healthy Humans Reduces Sympathetic Nerve Activity

BackgroundVagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimer's disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of the mechanisms involved.ObjectiveWe investigated a non-invasive method of VNS through electrical stimulation of the auricular branch of the vagus nerve distributed to the skin of the ear – transcutaneous VNS (tVNS) and measured the autonomic effects.MethodsThe effects of tVNS parameters on autonomic function in 48 healthy participants were investigated using heart rate variability (HRV) and microneurography. tVNS was performed using a transcutaneous electrical nerve stimulation (TENS) machine and modified surface electrodes. Participants visited the laboratory once and received either active (200 μs, 30 Hz; n = 34) or sham (n = 14) stimulation.ResultsActive tVNS significantly increased HRV in healthy participants (P = 0.026) indicating a shift in cardiac autonomic function toward parasympathetic predominance. Microneurographic recordings revealed a significant decrease in frequency (P = 0.0001) and incidence (P = 0.0002) of muscle sympathetic nerve activity during tVNS.ConclusiontVNS can increase HRV and reduce sympathetic nerve outflow, which is desirable in conditions characterized by enhanced sympathetic nerve activity, such as heart failure. tVNS can therefore influence human physiology and provide a simple and inexpensive alternative to invasive VNS.     

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference

Background and objectivesThe orally active dual OX₁R and OX₂R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.Patients and methodsProspective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18–64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated.ResultsFrom 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (−26.8 min and −19.5 min, respectively; both p < 0.0001); subjective WASO also decreased over the two-week treatment period (p = 0.0006). Objective and subjective total sleep time (TST) were increased with almorexant 200 mg (p < 0.0001). Almorexant 200 mg significantly reduced objective and subjective latency to persistent sleep and latency to sleep onset at initiation of therapy, and provided longer duration of sleep stages with no suppression of slow-wave sleep. No impaired next-day performance, rebound insomnia, or withdrawal effects were observed. Adverse events were similar with almorexant and placebo.ConclusionAlmorexant reduced time to sleep onset and maintained sleep without residual effects on next-day performance or safety concerns. This study provides further support for the role of the endogenous orexin system in insomnia disorder.ClinicalTrials.gov registrationNCT00608985.     

Distal muscle activity alterations during the stance phase of gait in restless leg syndrome (RLS) patients

ObjectiveTo assess if there is a circadian variation in electromyographical (EMG) muscle activity during gait in restless legs syndrome (RLS) patients and healthy control participants.MethodsGait assessment was done in 14 RLS patients and 13 healthy control participants in the evening (PM) and the morning (AM). Muscle activity was recorded bilaterally from the tibialis anterior (TA), lateral gastrocnemius (GL), rectus femoris (RF) and biceps femoris (BF) muscles.ResultsA circadian variation during the stance phase in only TA (PM > AM, p < 0.005) and BF (PM < AM, p = 0.008) activity was observed in control participants. Conversely no circadian variation was seen in any muscles in the RLS patients. RLS patients had an increased TA and GL activity (RLS > Controls, p < 0.05) during early stance and decreased GL activity (RLS < Controls, p < 0.01) during terminal stance in comparison to control participants in the evening. No other significant differences were noted between RLS patients and control participants. Activation of GL during the swing phase was noted in 79% of RLS patients and in 23% of control participants in the morning compared to 71% and 38% in the evening, respectively.ConclusionEMG muscle activity shows no circadian variation in RLS patients. Evening differences in gait muscle activation patterns between RLS patients and control participants are evident. These results extend our knowledge about alterations in spinal processing during gait in RLS. A possible explanation for these findings is central pattern generator sensitization caused by increased sensitivity in cutaneous afferents in RLS patients.     

Development of a clinician-administered National Institutes of Health-Brief Fatigue Inventory: A measure of fatigue in the context of depressive disorders

ObjectiveFatigue is a complex, multidimensional condition. Although it is often associated with depression, it is not known whether it has a distinct network from depression or whether it can be clinically evaluated, separately. This study describes preliminary findings in the development of a brief, clinician-administered instrument to measure fatigue in the context of depressive disorders using items from existing clinician-administered depression and mania scales.MethodsBased on items from prior fatigue measurements, items were selected from the Hamilton Depression Rating Scale (HDRS), Montgomery–Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale, and Structured Interview Guide for HDRS with Atypical Depression. The final items composed the NIH-Brief Fatigue Inventory (NIH-BFI). Responses from 89 depressed adults collected pre- and post-antidepressant therapy (ADT) determined the reliability and consistency of the NIH-BFI using Cronbach's alpha and principal components analysis (PCA). Correlations of the NIH-BFI and fatigue items from other scales before and after ADT explored validity.ResultsThe 7-item NIH-BFI had Cronbach alphas ranging from 0.81 to 0.88 and PCA indicating a single dimension. The NIH-BFI score was strongly correlated (r = 0.73, p < 0.001) with fatigue items from Beck Depression Index, with MADRS without fatigue items (r = 0.77, p < 0.001), and HDRS without fatigue items (pre: r = 0.69, p < 0.001).ConclusionsPreliminary findings show support for internal consistency reliability and validity of the NIH-BFI, a clinician-administered measure of fatigue. Further testing in other clinical populations is recommended to obtain additional information on reliability and validity. The NIH-BFI provides a method for clinician-rated fatigue that may be a separate from depression.     

Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy

BackgroundSevere putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA.MethodsPost-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA).ResultsThe PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p < 0.0001). An index of innervation (the sum of DOPA + Cys-DOPA) averaged 63% of control (p = 0.01).InterpretationBased on patterns of parent and cysteinyl catechols in putamen, PD and MSA involve decreased vesicular uptake and decreased LAAAD activity in the residual dopaminergic terminals. The combination seems to contribute importantly to dopamine depletion in these diseases.     

The association between daytime napping and risk of diabetes: a systematic review and meta-analysis of observational studies

ObjectiveTo investigate the association between daytime napping and prevalent/incident diabetes mellitus (DM) based on systematic review and meta-analytic data.MethodsThe electronic databases of Embase, Medline, Pubmed and Web of Science were searched. Relevant studies were extracted by two reviewers independently. The associations between daytime napping (irrespective of duration), long nap (≥1 h/day) and short nap (<1 h/day), and risk of DM were assessed according to study types. Overall estimates were pooled using either fixed- or random-effect with inverse variance meta-analysis. Heterogeneity of included studies was assessed using the I² test and possible cause of the heterogeneity was examined by meta-regression analyses.ResultsTen studies (four cross-sectional and six longitudinal cohort) comprising a total of 304,885 individuals and 20,857 cases of DM were included in the systematic review, with an average napping prevalence of 47%. Nappers were found to have increased risk of DM in both cross-sectional and cohort studies. However, significant heterogeneity was present. Long nap (≥1 h/day) was associated with both prevalent and incident DM; in particular, those with a daily nap over 1 h had a 31% increased risk of developing DM during follow-up (95% confidence interval: 2–67%). Conversely, no such association was found in individuals with short naps (<1 h/day) in cohort studies.ConclusionsLong daytime napping over 1 h per day was associated with increased risk of both prevalent and incident DM. Further studies are needed to confirm the findings.     

The short and long of adolescent sleep: the unique impact of day length

Study objectivesVariation in day length is proposed to impact sleep, yet it is unknown whether this is above the influence of behavioural factors. Day length, sleep hygiene, and parent-set bedtime were simultaneously explored, to investigate the relative importance of each on adolescents’ sleep.MethodsAn online survey was distributed in four countries at varying latitudes/longitudes (Australia, The Netherlands, Canada, Norway).ResultsOverall, 711 (242 male; age M = 15.7 ± 1.6, range = 12–19 yrs) adolescents contributed data. Hierarchical regression analyses showed good sleep hygiene was associated with earlier bedtime, shorter sleep latency, and longer sleep (β = −0.34; −0.30; 0.32, p < 0.05, respectively). Shorter day length predicted later bedtime (β = 0.11, p = 0.009), decreased sleep latency (β = −0.21, p < 0.001), and total sleep (β = −0.14, p = 0.001). Longer day length predicted earlier bedtimes (β = −0.11, p = 0.004), and longer sleep (β = 0.10, p = 0.011).ConclusionsSleep hygiene had the most clinical relevance for improving sleep, thus should be considered when implementing adolescent sleep interventions, particularly as small negative effects of shorter day length may be minimised through sleep hygiene techniques.     

Association between nighttime sleep duration,midday naps,and glycemic levels in Japanese patients with type 2 diabetes

ObjectivesTo clarify the relationship between nighttime sleep duration, midday naps, and glycemic control in Japanese patients diagnosed with type 2 diabetes (n = 355) or impaired glucose tolerance (n = 43).MethodsA total of 398 patients completed a self-administered questionnaire on sleep duration/quality and were divided into five groups according to their self-reported nighttime sleep duration: <5 h, 5–6 h, 6–7 h, 7–8 h, and >8 h. Each group was further divided into two subgroups each according to the presence or absence of midday naps. Poor glycemic control was defined as HbA1c ≥ 7.0%.ResultsShort nighttime sleep (<5 h), poor sleep induction, daytime sleepiness, and low sleep satisfaction were associated with high HbA1c levels. HbA1c was higher in the short nighttime sleep/no nap group than in non-nappers with different nighttime sleep duration, whereas the short nighttime sleep/nap group showed similar HbA1c levels to the other nap subgroups. In multivariate logistic regression models, after adjusting for a number of potential confounders, short (<5 h) nighttime sleep without nap was significantly associated with poor glycemic control compared with 6–7 h nighttime sleep without nap (OR [95% CI]: 7.14 [2.20–23.20]). However, taking naps reduced this risk for poor glycemic control in short sleepers. Other risk factors for poor glycemic control were low sleep satisfaction (1.73 [1.10–2.70]) and poor sleep induction (1.69 [1.14–2.50]).ConclusionsPoor sleep quality and quantity could aggravate glycemic control in type 2 diabetes. Midday naps could mitigate the deleterious effects of short nighttime sleep on glycemic control.Clinical trials registrationUMIN 000017887.     

Smartphone-based tactile cueing improves motor performance in Parkinson's disease

IntroductionVisual and auditory cueing improve functional performance in Parkinson's disease (PD) patients. However, audiovisual processing shares many cognitive resources used for attention-dependent tasks such as communication, spatial orientation, and balance. Conversely, tactile cues (TC) may be processed faster, with minimal attentional demand, and may be more efficient means for modulating motor-cognitive performance. In this study we aimed to investigate the efficacy and limitations of TC for modulating simple (heel tapping) and more complex (walking) motor tasks (1) over a range of cueing intervals, (2) with/without a secondary motor task (holding tray with cups of water).MethodsTen PD patients (71 ± 9 years) and 10 healthy controls (69 ± 7 years) participated in the study. TCs was delivered through a smart phone attached to subjects' dominant arm and were controlled by a custom-developed Android application.ResultsPD patients and healthy controls were able to use TC to modulate heel tapping (F(3.8,1866.1) = 1008.1, p < 0.001), and partially modulate walking (F(3.5,1448.7) = 187.5, p < 0.001) tasks. In the walking task, PD patients modulated performance over a narrower range of cueing intervals (R² = 0.56) than healthy controls (R² = 0.84; group difference F(3.5,1448.7) = 8.6, p < 0.001). TC diminished synchronization error associated with performance of secondary motor task during walking in PD patients and healthy controls (main effect of Task (F(1,494) = 0.4; p = 0.527), Task X Group interaction (F(1,494) = 0.5; p = 0.493)).ConclusionThis study expands modalities of TC usage for movement modulation and motor-cognitive integration in PD patients. The smartphone TC application was validated as a user-friendly movement modulation aid.     

Suppression of ATP-induced excitability in rat small-diameter trigeminal ganglion neurons by activation of GABAB receptor

The aim of the present study was to investigate whether a GABA_B receptor agonist could modulate ATP-activated neuronal excitability of nociceptive TRG neurons using perforated whole-cell patch-clamp and immunohistochemical techniques. Immunohistochemical analysis revealed that 86% of P₂X₃ receptor-immunoreactive, small-diameter TRG neurons co-expressed GABA_B receptor. Under voltage-clamp conditions (V_h = −60 mV), application of ATP activated the inward current in acutely isolated rat TRG neurons in a dose-dependent manner (10–50 μM) and this current could be blocked by pyridoxal-phosphate-6-azophenyl-27,47-disulfonic acid (PPADS) (10 μM), a selective P₂ purinoreceptor antagonist. The peak amplitude of ATP-activated currents was significantly inhibited after application of GABA_B receptor agonist, baclofen (10–50 μM), in a concentration-dependent and reversible manner. The baclofen-induced inhibition of ATP-activated current was abolished by co-application of 3-amino-2 (4-chlorophenyl)-2hydroxypropysufonic acid) saclofen, a GABA_B receptor antagonist (50 μM). Under current-clamp conditions, application of 20 μM ATP significantly depolarized the membrane potential resulting in increased mean action potential frequencies, and these ATP-induced effects were significantly inhibited by baclofen and these effects were antagonized by co-application of saclofen. Together, the results suggested that GABA_B receptor activation could inhibit the ATP-induced excitability of small-diameter TRG neurons activated through the P₂X₃ receptor. Thus, the interaction between P₂X₃ and GABA_B receptors of small-diameter TRG neuronal cell bodies is a potential therapeutic target for the treatment of trigeminal nociception.     

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke

BackgroundKnowledge available about the relationship between obstructive sleep apnea (OSA) and cognitive impairment after stroke is limited. The evolution of OSA and cognitive performance after stroke is not sufficiently described.MethodsWe prospectively enrolled and examined acute stroke patients without previously diagnosed OSA. The following information was collected: (1) demographics, (2) sleep cardio-respiratory polygraphy (PG) at 72 h, day seven, month three, and month 12 after stroke, (3) post-stroke functional disability tests at entry and at months three and 12, and (4) cognition (attention and orientation, memory, verbal fluency, language, and visual-spatial abilities) using the revised Addenbrooke's Cognitive Examination (ACE-R) at months three and 12.ResultsOf 68 patients completing the study, OSA was diagnosed in 42 (61.8%) patients. The mean apnea/hypopnea index (AHI) at study entry of 21.0 ± 13.7 spontaneously declined to 11.6 ± 11.2 at month 12 in the OSA group (p < 0.0005). The total ACE-R score was significantly reduced at months three (p = 0.005) and 12 (p = 0.004) in the OSA group. Poorer performance on the subtests of memory at months 3 (p = 0.039) and 12 (p = 0.040) and verbal fluency at months 3 (p < 0.005) and 12 (p < 0.005) were observed in the OSA group compared to non-OSA group. Visual-spatial abilities in both the OSA (p = 0.001) and non-OSA (p = 0.046) groups and the total ACE-R score in the OSA (p = 0.005) and non-OSA (p = 0.002) groups improved.ConclusionsA high prevalence of OSA and cognitive decline were present in patients after an acute stroke. Spontaneous improvements in both OSA and cognitive impairment were observed.     

Focused Ultrasound-mediated Non-invasive Brain Stimulation: Examination of Sonication Parameters

BackgroundTranscranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation.ObjectiveThe objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague–Dawley rats.MethodsWe transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency.ResultsWe observed that motor responses were elicited at minimum threshold acoustic intensities (4.9–5.6 W/cm² in spatial-peak pulse-average intensity; 2.5–2.8 W/cm² in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1–5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication.ConclusionOur results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.     

Sleep duration on workdays or nonworkdays and cardiac–cerebral vascular diseases in Southern China

ObjectivesThis study aimed to assess the relationship between sleep duration on work or nonworkdays and myocardial infarction (MI) and stroke in Southern China.MethodsA cross-sectional survey was conducted among 15,364 participants of age ≥15 years in Southern China from November 2013 to August 2014. Data on self-reported duration of sleep on workdays or nonworkdays as well as history of MI and stroke were collected in the questionnaire. The subjects were examined for weight, height, waist circumference, and blood pressure. Multivariate logistic regression analyses were performed to evaluate the association of sleep duration with MI and stroke.ResultOverall, compared with a sleep duration of 6–8 h, individuals who slept <6 h on workdays and nonworkdays were associated with increased risk for MI (odds ratio [OR] = 3.17, 2.04). Furthermore, individuals who slept >8 h on workdays and nonworkdays were associated with an increased risk for stroke (OR = 1.86, 1.54). Although this association persisted in men and subjects aged <65 years, we also observed that long sleep duration on workdays was associated with MI, especially among women, and short sleep duration on nonworkdays was associated with stroke among those aged 65 years or older. Participants with abnormal sleep duration and hypertension had higher risk of MI and stroke. Sleep debt was independently associated with MI risk, but not stroke (OR = 1.40; 95% confidence interval [CI]: 1.06–1.86), specifically among men aged <65 years.ConclusionsCompared with a sleep duration of 6–8 h, both short and long sleep duration were associated with the prevalence of MI and stroke and these associations were more pronounced among hypertensive persons, and tended to vary by age and sex. Moreover, sleep debt was linked to greater MI risk among men aged <65 years. These findings suggest that we should develop a healthy biological clock.     

Concurrent insomnia and habitual snoring are associated with adverse pregnancy outcomes

ObjectivesPregnant women report disturbed sleep, including habitual snoring and insomnia. The co-occurrence among non-pregnant cohorts is 30%–50% with increased risk for adverse health outcomes. To date, no study has examined the comorbid status or impact in pregnant women.MethodsThe prevalence of insomnia (INS) and habitual snoring (HS) were examined in 439 women in the third trimester (34.1 ± 3.7 weeks). Habitual snoring (snoring ≥3 times/week) was self-reported. Insomnia was determined using the Insomnia Symptom Questionnaire (ISQ).ResultsFour groups emerged: HS−/ISQ− (n = 161; 36.7%), HS−/ISQ+ (n = 146; 33.3%), HS+/ISQ− (n = 63; 14.4%), and HS+/ISQ+ (n = 69; 15.7%). Logistic regression models revealed both independent associations, as well as comorbid HS/INS status with excessive daytime sleepiness (aOR 3.8, 95%CI 2.3–6.5, p < 0.001; aOR 2.2, 95%CI 1.1–4.4, p = 0.02; aOR 7.2, 95%CI 3.7–14.0, p < 0.001, respectively). Only comorbid HS/INS was associated with gestational hypertension (aOR 3.2 95%CI 1.0–10.6, p = 0.048). Insomnia alone and HS alone were associated with a baby born large for gestational age (aOR 2.9 95%CI 1.2–7.1, p = 0.019 and aOR 3.5, 95%CI 1.1–11.1, p = 0.034 respectively) but however, the comorbid state was not significantly associated with LGA. Only women with HS alone were at increased odds of having an unplanned cesarean section (aOR 2.2 95%CI 1.0–4.6, p = 0.046).ConclusionsBoth insomnia alone and comorbid insomnia/habitual snoring were associated with adverse outcomes even after accounting for confounders. These findings are clinically relevant since adverse pregnancy outcomes may have severe consequences for both mother and baby. In order to mitigate these outcomes, identifying viable treatment(s) for women at risk should be considered a high priority.     

Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?

α-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score ≤27 or Alzheimer's Disease Dementia Screening Interview score ≥2 (cognitive outcome). Median disease duration at baseline was 3.3 years and median lag time from baseline to follow-up was 7.8 years. Paradoxically, REP1 genotypes associated with increased risk of developing PD and increased SNCA expression were associated with better motor (HR = 0.87, p = 0.046, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.020, covariate-adjusted time-scale analysis) and cognitive outcomes (HR = 0.90, p = 0.12, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.023, covariate-adjusted time-scale analysis). Our findings raise the possibility that SNCA has a dual, opposing, and time-dependent role. This may have implications for the development of therapies that target SNCA expression.     

The effect of sleep duration and sleep quality on hypertension in middle-aged and older Chinese: the Dongfeng-Tongji Cohort Study

ObjectiveTo examine the independent and combined associations of sleep duration and sleep quality with hypertension in a middle-aged and older Chinese population.MethodsWe included 21,912 individuals aged 62.2 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Sleep duration was self-reported and sleep quality was evaluated with questions designed according to the Pittsburgh Sleep Quality Index. Hypertension was defined as blood pressure ≥140/90 mmHg, or self-reported physician diagnosis of hypertension, or self-reported current use of antihypertensive medication.ResultsIn the cross-sectional analyses, the odds ratio of hypertension prevalence was significantly elevated (OR = 1.13, 95% CI = 1.03–1.24) in those who slept less than 7 h after adjusting for sex, age, body mass index, midday napping, cigarette smoking and sleep quality. It was particularly evident among males (OR = 1.19, 95% CI = 1.01–1.40) and individuals who were thin (OR = 2.00, 95% CI = 1.01–3.93) with full adjustment. The association was also found for sleep duration of 9∼<10 h after adjusting various covariates (OR = 1.14, 95% CI = 1.04–1.27). In addition, impaired sleep quality was only associated with hypertension in obese individuals (OR = 1.25, 95% CI = 1.02–1.50), not in other subgroups. However, no significant association was detected in any category of sleep duration or sleep quality in all models in the prospective analyses, and the results remained unchanged in the subgroup analyses of sex, age and body mass index.ConclusionsThe results of this study provide limited support for association of sleep duration and sleep quality with hypertension in middle-aged and older Chinese. Further studies are needed to confirm the results.     

Lithium increases platelet serine-9 phosphorylated GSK-3β levels in drug-free bipolar disorder during depressive episodes

BackgroundGlycogen synthase kinase-3 β (GSK3β) is an intracellular enzyme directly implicated in several neural processes relevant to bipolar disorder (BD) pathophysiology. GSK3β is also an important target for lithium and antidepressants. When phosphorylated at serine-9, GSK3β becomes inactive. Few studies evaluated serine-9 phosphorylated GSK3β (phospho-GSK3β) levels in BD subjects in vivo and no study has assessed it specifically in bipolar depression. Also, the effect of lithium monotherapy on GSK3β has never been studied in humans.MethodsIn 27 patients with bipolar depression, total GSK3β and phospho-GSK3β were assessed in platelets by enzyme immunometric assay. Subjects were evaluated before and after 6 weeks of lithium treatment at therapeutic levels. Healthy subjects (n = 22) were used as a control group.ResultsNo differences in phospho-GSK3β or total GSK3β were observed when comparing drug-free BD subjects in depression and healthy controls. Baseline HAM-D scores were not correlated with phospho-GSK3β and total GSK3β levels. From baseline to endpoint, lithium treatment inactivated GSK3β by significantly increasing phospho-GSK3β levels (p = 0.010). Clinical improvement (baseline HAM-D — endpoint HAM-D) negatively correlated with the increase in phospho-GSK3β (p = 0.03).ConclusionThe present results show that lithium inactivates platelet GSK3β in BD during mood episodes. No direct association with pathophysiology of BD was observed. Further studies are needed to clarify the role of GSK3β as a key biomarker in BD and its association with treatment response as well as the relevance of GSK3β in other neuropsychiatric disorders and as a new therapeutic target per se.