Disturbances In Parkinson's Disease Research Articles

Brain MRI morphometric analysis in Parkinson\u2019s disease patients with sleep disturbances

BackgroundSleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients.MethodsTwenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software.ResultsPD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson’s disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons.ConclusionsPD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas.

Peripheral and central autonomic nervous system: does the sympathetic or parasympathetic nervous system bear the brunt of the pathology during the course of sporadic PD?

It is a well-established fact that the sympathetic, parasympathetic and enteric nervous systems are affected at early stages in Parkinson's disease (PD). However, it is not yet clarified whether the earliest pathological events preferentially occur in any of these three divisions of the autonomic nervous system (ANS). Significant involvement of the peripheral autonomic nervous system of the heart and gastrointestinal tract has been documented in PD. Accumulating evidence suggests that the PD pathology spreads centripetally from the peripheral to central nervous system through autonomic nerve fibers, implicating the ANS as a major culprit in PD pathogenesis and a potential target for therapy. This study begins with a brief overview of the structures of the central and peripheral autonomic nervous system and then outlines the major clinicopathological manifestations of cardiovascular and gastrointestinal disturbances in PD.

Efficacy of Yokukansankachimpihange on sleep disturbance in Parkinson's disease: A study protocol of a randomized, double blind, placebo-controlled pilot trial.

Introduction:Parkinson's disease (PD) is a progressive neurodegenerative disorder that includes motor and nonmotor symptoms. Sleep disturbance is known to decrease the quality of life in patients with PD, and there are limitations to the pharmacotherapy currently in use. Therefore, complementary treatment therapies are required to address these limitations. The traditional herbal medicines Yokukansan (YKS) and Yokukansankachimpihange (YKSCH) have been used to treat insomnia and night crying in children, suggesting their effectiveness against sleep disturbance in patients with PD. We will evaluate whether YKSCH improves sleep disturbance in PD and will identify YKS-related changes in hemodynamic parameters, and neurotransmitter and hormone levels in patients with PD experiencing sleep disturbance.Methods:We will conduct a randomized, double-blinded, placebo-controlled parallel trial in 34 patients with PD and sleep disturbance, randomly allocating the patients to either placebo-control (n = 17) or treatment groups (n = 17). The total study period will be 16 weeks; administration of YKSCH or placebo, as intervention, will be performed for a 12-week period, and follow-up will be performed over a 4-week period. All subjects will undergo conventional treatment, and be required to maintain a regular medication schedule throughout the study period. The primary outcome measure will be the Scales for Outcomes in PD-Sleep Scale score, and the secondary outcome measures will be polysomnography results, findings from instruments related to sleep disorders, neurotransmitter and hormone levels, and hemodynamic changes in the brain cortex.Discussion and conclusions:This trial will evaluate the effectiveness and safety of YKSCH for sleep improvement in PD with sleep disturbance, and investigate the underlying mechanism of action. We expect improvement in the scores for subjective and objective sleep scales, hemodynamic changes in prefrontal cortical activity, and changes in neurotransmitter and hormone levels. The findings will provide insight into the mechanism underlying the therapeutic effect of YKSCH in PD, and lay the foundation for further studies on whether YKSCH improves sleep disturbance in PD.Trial registration number:Clinical Research Information Service (KCT0002869).

Nocturia in Parkinson's Disease: Why Does It Occur and How to Manage?

Nocturia is one of the commonest nonmotor symptoms in Parkinson's disease (PD) and has a significant impact on quality of life both for patients and their carers. There exists a relation between nocturia and poor sleep quality, falls, and institutionalization. Nocturia may manifest as a result of reduced functional bladder capacity or nocturnal polyuria; however, most often the cause is multifactorial. Disorders of circadian rhythm regulation are known to occur with sleep disturbances in PD may also contribute to nocturia. In this review, an overview of the assessment and management of nocturia in patients with PD is presented. History taking, medication review, and a bladder diary form the cornerstone of the evaluation. Urinalysis, ultrasonography, and urodynamic studies help to assess the cause for lower urinary tract symptoms and exclude concomitant pathologies, such as bladder outlet obstruction. Antimuscarinic medications are the first-line treatment for the overactive bladder; however, caution is needed when using these medications in individuals predisposed to cognitive impairment. Desmopressin is effective for managing nocturnal polyuria. An individualized approach is recommended to optimize the management of nocturia in PD.

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies.

Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

SUMO-regulated mitochondrial function in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by cardinal motor signs such as rigidity, bradykinesia or rest tremor that arise from a significant death of dopaminergic neurons. Non-dopaminergic degeneration also occurs and it seems to induce the deficits in olfactory, emotional, and memory functions that precede the classical motor symptoms in PD. Despite the majority of PD cases being sporadic, several genes have previously been associated with the hereditary forms of the disease. The proteins encoded by some of these genes, including α-synuclein, DJ-1, and parkin, are modified by small ubiquitin-like modifier (SUMO), a post-translational modification that regulates a variety of cellular processes. Among the several pathogenic mechanisms proposed for PD is mitochondrial dysfunction. Recent studies suggest that SUMOylation can interfere with mitochondrial dynamics, which is essential for neuronal function, and may play a pivotal role in PD pathogenesis. Here, we present an overview of recent studies on mitochondrial disturbance in PD and the potential SUMO-modified proteins and pathways involved in this process. SUMOylation, a post-translational modification, interferes with mitochondrial dynamics, and may play a pivotal role in Parkinson's disease (PD). SUMOylation maintains α-synuclein (α-syn) in a soluble form and activates DJ-1, decreasing mitochondrial oxidative stress. SUMOylation may reduce the amount of parkin available for mitochondrial recruitment and decreases mitochondrial biogenesis through suppression of peroxisomal proliferator-activated receptor-γ co-activator 1 α (PGC-1α). Mitochondrial fission can be regulated by dynamin-related protein 1 SUMO-1- or SUMO-2/3-ylation. A fine balance for the SUMOylation/deSUMOylation of these proteins is required to ensure adequate mitochondrial function in PD.

Freezing of gait is associated with increased saccade latency and variability in Parkinson's disease.

Freezing of gait (FOG) is a locomotor disturbance in Parkinson disease (PD) related to impaired motor automaticity. In this study, we investigated the impact of freezing on automaticity in the oculomotor system using an anti-saccade paradigm. Subjects with PD with (PD-FOG, n=13) and without (PD-NON, n=13) FOG, and healthy age-matched controls (CTRL, n=12) completed automatic pro-saccades and non-automatic anti-saccades. Primary outcomes were saccade latency, velocity, and gain. PD-FOG (pro-saccade latency=271ms, anti-saccade latency=412ms) were slower to execute both types of saccades compared to PD-NON (253ms, 330ms) and CTRL (246ms, 327ms). Saccade velocity and gain variability was also increased in PD-FOG. Saccade performance was affected in PD-FOG for both types of saccades, indicating differences in automaticity and control in the oculomotor system related to freezing. These results and others show that FOG impacts non-gait motor functions, suggesting global motor impairment in PD-FOG.

Melatonin attenuates hLRRK2-induced sleep disturbances and synaptic dysfunction in a Drosophila model of Parkinson's disease.

Sleep problems are the most common non-motor symptoms in Parkinson's disease (PD), and are more difficult to treat than the motor symptoms. In the current study, the role of human leucine-rich repeat kinase 2 (hLRRK2), the most common genetic cause of PD, was investigated with regards to sleep problems, and the therapeutic potential of melatonin in hLRRK2‑associated sleep problems was explored in Drosophila. hLRRK2 was selectively expressed in the mushroom bodies (MBs) in Drosophila and sleep patterns were measured using the Drosophila Activity Monitoring System. MB expression of hLRRK2 resulted in sleep problems, presynaptic dysfunction as evidenced by reduced miniature excitatory postsynaptic current (mEPSC) and excitatory postsynaptic potential (EPSP) frequency, and excessive synaptic plasticity such as increased axon bouton density. Treatment with melatonin at 4mM significantly attenuated the sleep problems and rescued the reduction in mEPSC and EPSP frequency in the hLRRK2 transgenic flies. The present study demonstrates that MB expression of hLRRK2 in flies recapitulates the clinical features of the sleep disturbances in PD, and that melatonin attenuates hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of melatonin in PD patients carrying LRRK2 mutations.

Assessment of Nocturnal and Daytime Sleep disturbances among Elderly Parkinsonism Patients in Baghdad City

Background: Sleep disturbances are one of the most common of the non-motor complications of Parkinson's disease (PD), and increase in frequency with advancing disease. As many as 98% of patients with PD may suffer at some time from nocturnal symptoms, that can disturb their sleep. The causes of sleep disturbance in PD are numerous, and many patients may have several factors that contribute. These disorders can be broadly categorized into those that involve nocturnal sleep and daytime manifestations such as excessive daytime sleepiness. Objectives: To assess the levels of disturbances of nocturnal and daytime sleep of the Parkinson's disease patients in the city of Baghdad and to find out relationship between these levels and some demographic characteristics of patients. Methodology: A descriptive study was conducted between the ninth of September, 2013 and 15th of December 2013. A purposive non-probability sample of 100 elderly patients who are diagnosed with Parkinson's disease andanother 75 aged matched healthy controls were recruited to participate in the study. To reach the objectives ofthis study a questionnaire was constructed. The present questionnaire consists of two parts; demographiccharacteristics; gender, age, and duration of illness; and 15 items as a part of Parkinson's disease Sleep Scale(PDSS) for measuring levels of sleep disturbances. Results: The results indicate that all the patients with Parkinson's disease have different levels of sleepdisturbances: 55.0% with severe level, 32.0% with moderate level, and only 13.0% with mild level. There is asignificant association between levels of sleep disturbances and age and duration of illness. Also the resultsrevealed that there were a wide difference between the Parkinson's disease group and matched healthy controlgroup regarding the sub-categories of sleep disturbances. Conclusions: The results of the study indicated that more than half of PD patients had severe level of sleepdisturbance; there were significant relationships between severity of sleep disturbances and age and duration ofdisease; and finally there was a difference between PD participants and matched controls group. Recommendations: Establishing specialized centers which give daily cares for patients with Parkinson'sdisease, follow-up programs for each patient registered at these centers, and governmental financial supportfor those patients.

Parkinson's disease and sleep/wake disturbances.

Sleep disturbances are a common non-motor feature in patients with Parkinson's disease (PD). Early diagnosis and appropriate management are imperative for enhancing patient quality of life. Sleep disturbances can be caused by multiple factors in addition to age-related changes in sleep, such as nocturnal motor symptoms (rigidity, resting tremor, akinesia, tardive dyskinesia, and the "wearing off" phenomenon), non-motor symptoms (pain, hallucination, and psychosis), nocturia, and medication. Disease-related pathology involving the brainstem and changes in the neurotransmitter systems (norepinephrine, serotonin, and acetylcholine) responsible for regulating sleep structure and the sleep/wake cycle play a role in emerging excessive daytime sleepiness and sleep disturbances. Additionally, screening for sleep apnea syndrome, rapid eye movement sleep behavior disorder, and restless legs syndrome is clinically important. Questionnaire-based assessment utilizing the PD Sleep Scale-2 is useful for screening PD-related nocturnal symptoms. In this review, we focus on the current understanding and management of sleep disturbances in PD.

Deep brain stimulation does not provide long-term benefit to postural and gait disturbances in Parkinson disease

Deep brain stimulation does not provide long-term benefit to postural and gait disturbances in Parkinson disease

Does Integrative Medicine Enhance Balance in Aging Adults? Proof of Concept for the Benefit of Electroacupuncture Therapy in Parkinson's Disease

Background: Postural balance and potentially fall risk increases among older adults living with neurological diseases, especially Parkinson's disease (PD). Since conventional therapies such as levodopa or deep brain stimulation may fail to alleviate or may even worsen balance, interest is growing in evaluating alternative PD therapies. Objective: The purpose of the current study was to assess improvement in postural balance in PD patients following electroacupuncture (EA) as an alternative therapy. Methods: 15 aging adults (71.2 ± 6.3 years) with idiopathic PD and 44 healthy age-matched participants (74.6 ± 6.5 years) were recruited. The PD participants were randomly assigned (at a ratio of 2:1) to an intervention (n = 10) or to a control group (n = 5). The intervention group received a 30-min EA treatment on a weekly basis for 3 weeks, while the control group received a sham treatment. Outcomes were assessed at baseline and after the final therapy. Measurements included balance assessment, specifically the ratio of medial-lateral (ML) center-of-gravity (COG) sway to anterior-posterior (AP) sway (COG_ML/AP) and ankle/hip sway during eyes-open, eyes-closed, and eyes-open dual-task trials, the Unified Parkinson's Disease Rating Scale (UPDRS), as well as quality of life, concerns for fall, and pain questionnaires. Results: No difference was observed for the assessed parameters between the intervention and the control group at baseline. After treatment, an improvement in balance performance was observed in the intervention group. Compared with the healthy population, PD patients prior to treatment had larger COG_ML/AP sway with more dependency on upper-body movements for maintaining balance. Following EA therapy, COG_ML/AP sway was reduced by 31% and ankle/hip sway increased by 46% in the different conditions (p = 0.02 for the dual-task condition). The clinical rating revealed an overall improvement (p < 0.01) in mentation, behavior, and mood (UPDRS part I, 49%), activities of daily living (UPDRS part II, 46%), and motor examination (UPDRS part III, 40%). There was a significant reduction (p < 0.02) in the specific items regarding UPDRS fall status (67%) and rigidity (48%). Changes were small and nonsignificant in the controls (p > 0.29). Conclusions: This pilot study demonstrates improvement in rigidity and balance following EA. These preliminary results suggest EA could be a promising alternative treatment for balance disturbance in PD.

Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease

Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.

Alteration of Daily and Circadian Rhythms following Dopamine Depletion in MPTP Treated Non-Human Primates

Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([11C]-PE2I) and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed.

A Clinical Approach Towards Smell Loss in Parkinson's Disease

Impairment of olfaction is a characteristic feature of Parkinson's disease (PD). Recent data indicate that >90% of patients with PD are diagnosed with significant olfactory loss. The olfactory loss in PD has a bilateral and general character and all olfactory domains are involved. By clinical measurements, the olfactory deficit in PD is independent of disease severity and duration. Imaging studies however, point out that the olfactory impairment may be progressive in the early motor stages. Deficits in the sense of smell may precede clinical motor symptoms by years and can be used to assess the risk for developing PD in otherwise asymptomatic individuals. Numerous studies suggest that olfactory disturbances in PD may have diagnostic utility for the differentiation of PD from other movement disorders. This review summarizes the available information about the character of olfactory function in PD and possible therapeutic strategies. It indicates the advantageous use of olfactory probes as a contribution to early and differential diagnosis.

Imaging: What can it tell us about parkinsonian gait?

Functional neuroimaging has provided new tools to study cerebral gait control in Parkinson's disease (PD). First, imaging of blood flow functions has identified a supraspinal locomotor network that includes the (frontal) cortex, basal ganglia, brainstem tegmentum, and cerebellum. These studies also emphasize the cognitive and attentional dependency of gait in PD. Furthermore, gait in PD and related syndromes like progressive supranuclear palsy may be associated with dysfunction of the indirect, modulatory prefrontal-subthalamic-pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar input appears to be preserved and may contribute to the unflexible gait pattern in parkinsonian gait. Second, neurotransmitter and proteinopathy imaging studies are beginning to unravel novel mechanisms of parkinsonian gait and postural disturbances. Dopamine displacement imaging studies have shown evidence for a mesofrontal dopaminergic shift from a depleted striatum in parkinsonian gait. This may place additional burden on other brain systems mediating attention functions to perform previously automatic motor tasks. For example, our preliminary cholinergic imaging studies suggest significant slowing of gait speed when additional forebrain cholinergic denervation occurs in PD. Cholinergic denervation of the pedunculopontine nucleus and its thalamic projections have been associated with falls and impaired postural control. Deposition of β-amyloid may represent another non-dopaminergic correlate of gait disturbance in PD. These findings illustrate the emergence of dopamine non-responsive gait problems to reflect the transition from a predominantly hypodopaminergic disorder to a multisystem neurodegenerative disorder involving non-dopaminergic locomotor network structures and pathologies.

Disturbed sleep in Parkinson's disease: anatomical and pathological correlates

Abnormal sleep is a common feature of Parkinson's disease (PD) and prodromal disorders of sleep are frequent (e.g. restless legs syndrome and rapid eye movement sleep behaviour disorder). However, the exact pathological basis of disturbed sleep remains as yet undefined. To investigate this further, 32 PD cases were stratified into three groups: (1) PD with disturbed sleep, PD(S); (2) PD with dementia (PDD) and disturbed sleep, PDD(S); and (3) PD without disturbed sleep, PD(nS). The extent of α-synuclein (αSyn) and Alzheimer disease (AD)-type pathology [amyloid β peptide (Aβ) and tau] was assessed in 15 regions of the PD brain. The results demonstrate a significant association between disturbed sleep in PD and αSyn pathology in specific brainstem [locus coeruleus (P = 0.006) and raphe nuclei (P = 0.02)], hypothalamic [paramammillary nuclei (P = 0.04) and posterior nucleus (P = 0.02)], subcortical/limbic [amygdala (P = 0.03), thalamus (P = 0.01)] and cortical [entorhinal cortex (P = 0.01)] regions. A statistically significant increase of tau pathology was observed in the amygdala (P = 0.03), CA2 sector of the hippocampus (P = 0.01) and entorhinal cortex (P = 0.04) in PD cases with disturbed sleep. Pathological changes in these structures, residing in the brain circuitry relating to sleep physiology, strongly predict the presence of sleep disturbances in PD.

The study of subjective and objective evaluation of sleep disturbances in Parkinson's disease

Background Sleep disorder is one of the most common non-motor symptoms in Parkinson's disease (PD) patients. At present, there are subjective and objective tools to evaluate sleep disorders. Nevertheless, previous studies commonly used single subjective questionnaires or objective examinations. Therefore, we used the combinations of subjective and objective tools to analyze clinical characteristics of sleep disturbances in PD and investigated differences and consistence between subjective and objective tools. Methods One hundred and sixteen PD patients were eligible to participate into this study. All participants were evaluated by Pittsburgh Sleep Quality Index (PSQI), Unified Parkinson's Disease Rating Scale (UPDRS) in on condition, Hoehn-Yahr (H-Y) stage, Hamilton Depression Rating Scale (HAMD 24 items), Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), and underwent a video-polysomnography (Video-PSG). Results According to PSQI score of 116 PD patients, the proportion of PD patients with sleep disturbances (PSQI ≥ 7) was 50% (N = 58). Compared to PD patients without sleep disturbances, PD patients with sleep disturbances had lower score of MoCA (23.34 ± 3.50 vs 24.89 ± 3.52; t = 2.377, P = 0.019), higher score of UPDRSⅠ[4.00 (2.00, 5.00) vs 3.00 (2.00, 5.00); U = - 2.306, P = 0.021], UPDRSⅡ[12.00 (9.00, 16.00) vs 10.00 (6.00, 13.00); U = - 1.995, P = 0.046], higher levodopa equivalent daily dose [LED, (508.14 ± 335.85) vs (394.06 ± 236.40) mg/d; t = - 2.115, P = 0.037]. Although PD patients with sleep disturbances had more score of UPDSR Ⅲ and higher H-Y stage, the differences were not significant (P > 0.05). On the other hand, decreased total sleep time (TST), reduced sleep efficiency (SE), increased sleep latency (SL), decreased non-rapid eye movement (NREM) sleep stage Ⅱ time were found for PD patients with sleep disturbances (P 0.05, for all). The score of PSQI was positively correlated with the score of ESS (r = 0.200, P = 0.032), HAMD (r = 0.202, P = 0.030), UPDRSⅠ (rs = 0.266, P = 0.004) and Ⅱ (rs = 0.254, P = 0.007), LED (r = 0.213, P = 0.022), SL (rs = 0.211, P = 0.023). Moreover, the score of PSQI was negatively correlated with TST (r = -0.231, P = 0.003), SE (r = -0.192, P = 0.039) and MoCA (r = -0.236, P = 0.011). Conclusion PD patients with sleep disturbances had worse cognition impairment, more mood disorders, decreased activity of daily life. Meanwhile, most of PSG parameters were altered in PD patients with sleep disturbances. Moreover, the severity of sleep disturbances in PD patients was correlated with these factors. Overall sleep quality of PD patients assessed with the objective tool could be predicted by the subjective scale. However, to evaluate sleep architecture and other sleep disorders for PD patients, the objective tools (such as Video-PSG monitoring) are necessary to be used.

Gait freezing and speech disturbance in Parkinson’s disease

Gait freezing and speech disturbance are disabling axial features of Parkinson's disease (PD). However, the pathogenesis of these features remains unclear. We investigated the relation between changes in gait freezing and speech disturbance using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients with freezing (PDGF) and 9 without gait freezing were studied. Patients performed a 7-m back-and-forth walk in a baseline state and with visual and auditory cues. Gait velocity, stride length and cadence were evaluated using a three-dimensional gait analysis system. For speech evaluation, patients read ten sentences in a baseline state and with visual and auditory cues. The time delay of speech initiation, speech rate and the number of repetitions per sentence were quantified. In PDGF patients, the increase in gait velocity positively correlated with the decrease in the time delay of the speech initiation. Also, the increase in the gait velocity and cadence positively correlated with the decrease in the number of repetitions per sentence. The increase in the stride length positively correlated with the increase in speech rate. Lastly, the increase in stride length positively correlated with the decrease in the number of repetitions per sentence. These findings suggest that there is a common pathomechanism of gait freezing and speech disturbance in PD.

Reduction in Parkinson’s Disease Therapy Improved Punding But Not Feeling of Presence

Reduction in Parkinson’s Disease Therapy Improved Punding But Not Feeling of Presence