Function In Parkinson's Disease Patients Research Articles

Cognitive reserve moderates the relationship between sleep difficulties and executive functions in patients with Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor disturbances as well as non-motor symptoms, such as sleep and cognitive difficulties. Recent evidence has shown that, in patients with PD, sleep disturbances selectively correlate with specific cognitive functions, such as non-verbal reasoning, attention and executive functions, and language abilities.The present study aimed to test the hypothesis of Cognitive Reserve (CR) as a potential moderator in the relationship between sleep difficulties and cognitive performance in PD patients. Participants were asked to attend two sessions in which they were assessed for cognitive functions and reserve, as well as subjective sleep quality, excessive sleepiness, and symptoms of REM sleep behavior disorder (RBD) and insomnia.The results of preliminary correlations confirmed the presence of a significant negative correlation between sleep quality and cognitive performance. The results of the moderation analysis revealed a significant role for CR as a moderator of the negative association between RBD and executive functions. Specifically, a significant negative correlation was observed between sleep difficulties and executive performance only in patients with low CR. Overall, our results suggest that patients with PD with low to average CR levels could be considered to be more at risk of developing cognitive deficits in the presence of sleep difficulties.

Efficacy of Probiotics in Improving Motor Function and Alleviating Constipation in Parkinson's Disease: A Randomized Controlled Trial.

Parkinson's disease (PD) is one of the common neurodegenerative diseases, and there has been an increasing interest in the potential role of intestinal dysbiosis in its pathogenesis and related gastrointestinal complications such as constipation. This study aims to evaluate the effects of multi-strain probiotics on constipation and motor function in PD patients. This study was a blinded, randomized controlled trial (RCT) that involved 27 PD patients who were diagnosed with constipation according to the ROME IV criteria for functional constipation. The primary outcome measured before and after the intervention in both the placebo and probiotic groups was the frequency of defecation. Secondary outcomes evaluated were laxative use, sense of complete evacuation, Bristol Stool Scale for consistency, and Unified Parkinson's Disease Rating Scale (UPDRS) scale. The study lasted for eight weeks. Both groups also were educated about lifestyle modification. Of 30 included patients (15 in each group), 13 were women, and 17 were men. Three patients dropped out of the study. Between-group analysis showed that the frequency of bowel movements significantly increased in the probiotic group 4 [3 - 5] in comparison with 2 [2 - 3] in placebo (P = 0.02). Stool consistency also improved in the probiotic group (P = 0.04). However, there were no significant differences in other outcomes. The within-group analysis showed improvement in stool consistency in both probiotics and placebo groups (P = 0.01 and P = 0.007, respectively), while stool frequency and sense of complete evacuation significantly improved only in the probiotic group (P < 0.05). This study demonstrated that multi-strain probiotics could improve frequency, consistency, and sense of complete evacuation in PD patients, while there was no significant effect on motor functions in 8 weeks. It is suggested that additional studies be conducted on longer-term effects.

Neurological Insights into Sleep Disorders in Parkinson's Disease.

Parkinson's disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep-wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep-wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD.

A top-down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls.

Parkinson's disease (PD) is a complex neurodegenerative disease with motor and non-motor symptoms. Diagnosis is complicated by lack of reliable biomarkers. To individuate peptides and/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top-down platform based on HPLC-ESI-IT-MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin β4, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of α-defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S-cysteinylated and S-glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. α-defensins, histatin 1, oxidized S100A9, and P-B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin β4 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate-immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD.

Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson's disease based on metagenomic sequencing.

The role of the microbiota-gut-brain axis in Parkinson's disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD. Fresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed. The relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values. Our study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD.

Low-Field Magnetic Stimulation Alleviates MPTP-Induced Alterations in Motor Function and Dopaminergic Neurons in Male Mice.

Recent studies show that repetitive transcranial magnetic stimulation (rTMS) improves cognitive and motor functions in patients with Parkinson's Disease (PD). Gamma rhythm low-field magnetic stimulation (LFMS) is a new non-invasive rTMS technique that generates diffused and low-intensity magnetic stimulation to the deep cortical and subcortical areas. To investigate the potential therapeutic effects of LFMS in PD, we subjected an experimental mouse model to LFMS (as an early treatment). We examined the LFMS effect on motor functions as well as neuronal and glial activities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated male C57BL/6J mice. Mice received MPTP injection (30 mg/kg, i.p., once daily for 5 days) followed by LFMS treatment, 20 min each day for 7 days. LFMS treatment improved motor functions compared with the sham-treated MPTP mice. Further, LFMS significantly improved tyrosine hydroxylase (TH) and decreased glial fibrillary acidic protein (GFAP) levels in substantia nigra pars compacta (SNpc) and non-significantly in striatal (ST) regions. LFMS treatment improved neuronal nuclei (NeuN) levels in SNpc. Our findings suggest that early LFMS treatment improves neuronal survival and, in turn, motor functions in MPTP-treated mice. Further investigation is required to clearly define the molecular mechanisms by which LFMS improves motor and cognitive function in PD patients.

Gustatory dysfunction is related to Parkinson's disease: A systematic review and meta-analysis.

Olfactory dysfunction has been reported to be involved in Parkinson's disease (PD) pathogenesis. However, gustatory dysfunction in PD has not been evaluated as in-depth as olfactory dysfunction. We reviewed the previously published studies regarding gustatory function in PD patients and suggested the possibility that gustatory dysfunction may also be associated with PD. MEDLINE, Cochrane Library, Embase, and PubMed databases were searched for studies evaluating gustatory function in PD patients. We used the standardized mean difference and a 95% confidence interval (CI) as the effect analysis index regarding the taste strip test. The relative risk and 95% CI were used as the effect analysis index for the questionnaires and propylthiouracil (PTU)/phenylthiocarbamide (PTC) perception test. Statistical heterogeneity was assessed using forest plots, Cochran's Q, and the I2 statistic; heterogeneity was considered high when I2 was over 75%. Publication bias was assessed by funnel plots and the Egger bias test. We identified 19 articles that reported the results of gustatory function tests in PD patients and healthy controls. Most of these studies used various gustatory tests, including taste strips, questionnaires, taste solutions, PTU/PTC perception tests, and electrogustometry, and reported significantly lower gustatory function in PD patients than in the controls. However, several articles reported contradictory results. Based on these studies, gustatory dysfunction is closely related to PD. However, the number of studies and enrolled subjects was small, and a unified gustatory function test was lacking. Therefore, further studies with larger populations and normalized gustatory function tests are needed.

Association between prediabetes and cognitive function in Parkinson's disease.

It remains largely unknown whether prediabetes is related to cognitive impairment in Parkinson's disease (PD). This study aimed to assess the association between prediabetes and cognitive function in PD patients. In this cross-sectional study, 262 PD patients (age, 69.8±10.3 years; Hoehn-Yahr stage, 2.3±0.8) were classified into diabetes (glycated hemoglobin [HbA1c] ≥6.5% or previously diagnosed, n=76), prediabetes (5.7%-6.4%, n=90), or diabetes free (≤5.6%, n=96) groups. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. Both the diabetes and prediabetes groups had significantly lower MoCA scores (17.0±6.6 and 18.0±6.1, respectively) than the diabetes free group (20.0±5.7), even after adjusting for potential confounders (p=.002 and p=.008, respectively). In the combined group of prediabetes and diabetes free patients, higher HbA1c levels significantly correlated with lower MoCA scores (p=.031). There was a significant interaction of diabetes status with age, but not with the duration of PD, on cognitive function. In addition to diabetes, prediabetes may negatively affect cognitive function in PD patients. Further prospective longitudinal studies are necessary to clarify the impact of prediabetes on the cognitive trajectory of these patients.

Altered BDNF levels are associated with cognitive impairment in Parkinson's disease patients with depression

ObjectiveDepression and cognitive impairment are both common non-motor symptoms of Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) may play an important role in both cognitive function and depression. In this study, we examined BDNF levels, cognitive function, and the relationship between BDNF and cognitive function in PD patients with and without depressive symptoms, which has not been reported yet. MethodsWe recruited 96 PD patients with (n = 46) and without depression (n = 50) and 102 controls and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and BDNF levels in all groups. The Zung Self-Rating Depression Scale (SDS) was used to assess the severity of depression and the Hoehn-Yahr staging test was used to assess motor abilities in PD patients. ResultsBDNF levels were lower in patients with depressive symptoms than in patients without depressive symptoms (p<0.01). The RBANS total score and the immediate memory, language and attention scores were lower in patients with depressive than in patients without depressive (all p < 0.05). Multiple regression analysis showed that BDNF was independent contributor to immediate memory, language and RBANS total score in the patients with depressive symptoms. BDNF and SDS were independent contributors to attention, and SDS was an independent contributor to delay memory (all p < 0.001). ConclusionsBDNF may be involved in the pathophysiology of PD patients with depressive symptoms. Moreover, the association between BDNF and cognitive performance only in patients with depressive symptoms suggest a close relationship in BDNF, cognition and depressive symptoms in PD patients.

Enlarged perivascular spaces are linked to freezing of gait in Parkinson's disease.

ObjectiveFreezing of gait (FOG) is one of common and disabling gait impairments of Parkinson's disease (PD). White matter hyperintensity (WMH) and lacunes, as common manifestations of cerebral small vessel diseases (CSVD), have been reported to be associated with gait function in PD patients. However, in the cases with FOG which present with extensive WMH or lacunes, it actually is difficult to distinguish pure PD pathology from vascular origin or combined effects. So far little is known about the correlation between enlarged perivascular space (PVS) and FOG in PD patients. This study aims to explore the role of enlarged PVS in FOG in PD patients.MethodsA total of 95 patients with PD in the absence of obvious WMH and lacunes were included in our study, which were divided into PD-FOG (+) group and PD-FOG (-) group. Demographic and clinical data were investigated. Enlarged PVS in the centrum semiovale (CSO) and basal ganglia (BG) were assessed. The association between enlarged PVS and FOG in patients with PD was analyzed using the multivariate models and the Spearman's correlation.ResultsThere were 36 PD patients grouped into PD-FOG (+) (37.9%), with an older age, a longer PD disease duration, and larger numbers of enlarged PVS in CSO and BG compared with PD-FOG (-) group. The highest-severity degree of enlarged PVS burden in CSO was independently associated with FOG in patients with PD [adjusted odds ratio (OR), 3.869; p = 0.022 in multivariable model]. The percentages of FOG case increased accompanied by the aggravation of enlarged PVS located in CSO. The grade and count of enlarged PVS in CSO and BG both correlated with FOGQ score in PD patients.ConclusionEnlarged PVS, particularly in CSO, are associated with FOG in patients with PD, which provides a novel perspective for the mechanisms of FOG in PD.

Metabolite changes in prefrontal lobes and the anterior cingulate cortex correlate with processing speed and executive function in Parkinson disease patients.

BackgroundProcessing speed and executive function can be impaired in patients with Parkinson disease (PD). However, the neural factors related to the slowdown in processing speed and dysexecutive function in PD are not completely understood. The objective of this study is to investigate the metabolic changes of the frontal and anterior cingulate cortex (ACC) through the use of 1H magnetic resonance spectroscopy and to explore the association between cognitive function and metabolic ratios.MethodsIn this retrospective case-control study, we conducted neuropsychological assessments of executive function and information processing speed in healthy controls (HCs) and in patients with PD. Chemical information was obtained for the of N-acetyl-aspartate (NAA):creatine (Cr) ratio and the choline-containing compounds (Cho):Cr ratio within the bilateral prefrontal cortex and ACC. Using hierarchical multiple regression analysis, we analyzed the relationship between cognitive function and metabolic ratios in the bilateral prefrontal lobe and ACC in patients with PD.ResultsIn all, 59 patients with PD and 30 HCs were recruited. Patients with PD showed worse performance in executive function and processing speed compared with HCs (P<0.001). In patients with PD, the Cho:Cr ratios in the ACC (Z=2.20, P=0.028) and the right prefrontal cortex (t=2.16, P=0.034) were significantly increased. The hierarchical multiple regressions in patients with PD showed that the NAA:Cr ratio in the ACC correlated with the Stroop A completion times (P<0.05) and that the NAA:Cr ratio of the right prefrontal cortex correlated with the scores of the Wechsler Adult Intelligence Scale (WAIS)-Digit symbol test (P<0.05).ConclusionsInformation processing speed and executive function are impaired in patients with PD. Neuronal integrity and membrane turnover in the ACC and the right prefrontal cortex may be important factors in the slowdown of the information processing speed in patients with PD.

Sensory and Motor Visual Functions in Parkinson’s Disease with Respect to Freezing of Gait Symptoms

Freezing of gait (FOG) is considered to be a motor disorder symptom that affects some Parkinson Disease (PD) patients; however, it is hypothesized that sensory systems may also be involved in FOG. This review article summarizes the results from previous studies focusing on visual functions in PD patients. More emphasize will be focused on freezing of gait PD patients and whether visual functions are affected to greater amount among them than non-freezing of gait PD patients. Visual functions include high contrast visual acuity, low contrast visual acuity, contrast sensitivity, Vernier acuity, mesopic vision, stereopsis, motion perception, and vergence eye movements are all affected in PD patients, with FOG patients having more deficits in some of these functions. FOG patients also had larger impairments in non-dopaminergic mediated functions such as pupil light reflex and visual processing speed test, which suggests that FOG patients have greater impairment in two functions that involve cholinergic neurotransmitters. Whether these impairments are contributing to the FOG or just associated with FOG is uncertain.

The Deep Brain Stimulation Impairment Scale: A useful complement in assessment of well-being and functioning in DBS-patients – Results from a large multicentre survey in patients with Parkinson's disease

BackgroundDeep Brain Stimulation (DBS) has been proven to alleviate motor symptoms in Parkinson's Disease (PD). Regarding non-motor symptoms, however, inconsistencies have been reported, on whether DBS causes reductions in well-being and functioning. To assess motor and non-motor impairment in DBS-patients, the Deep Brain Stimulation Impairment Scale (DBS-IS) has been developed. Yet, the extent to which the DBS-IS detects impairment in DBS-patients and thus could serve as a useful tool that complements the PDQ-39 (gold standard) in assessment of well-being and functioning in PD-patients has not been shown. ObjectivesBy comparing DBS and non-DBS-patients we aimed to identify DBS-specific symptoms. We thereby aimed to show in how far the DBS-IS complements the PDQ-39 in assessing well-being and functioning in PD patients under DBS. MethodsIn a cross-sectional study, 186 DBS-patients were matched (for age, disease duration and sex) to 186 non-DBS-patients (N = 372) and the two groups were compared regarding well-being and functioning: Impairment was assessed via DBS-IS and overall Quality of Life (QoL) was assessed via PDQ-39. Additionally, we analyzed differences in impairment between age and disease duration clusters. ResultsDBS-patients showed significantly higher total impairment (DBS-IS) and significantly higher impairment on the subscales Postural Instability and Gait difficulties and speaking difficulties than non-DBS-patients. Impairment increased with age and disease duration and, overall, differences in impairment rose by age. Overall QoL (PDQ-39) was non-significantly lower in DBS-patients. ConclusionSince there is evidence that the PDQ-39 misses some DBS-specific symptoms, the DBS-IS is recommended to complement the PDQ-39 when assessing DBS-patients.

P 15 Long-term subthalamic deep brain stimulation modulates pathological beta oscillations in the AAV-A53T-Synuclein Parkinson's disease rat model

Introduction: Aberrant beta (13-35 Hz) synchrony within the cortico-basal ganglia circuit has been reported as disease-specific hallmark of human Parkinson's disease (PD). The suppression of pathologically enhanced beta oscillations following subthalamic deep brain stimulation (STN-DBS ) is considered to be a crucial mechanism mediating improved motor function in PD patients and animal models. However, it remains unclear how long-term STN-DBS modulates beta oscillations over time in PD models with ongoing dopaminergic neurodegeneration. To clarify, we performed 3 weeks of continuous STN-DBS in a pathologically-relevant preclinical AAV-A53T-αSynuclein PD rat model (A53T). This model is characterized by a gradual nigrostriatal degeneration and reflects clinical hallmarks of human PD, thus allowing us to study neuromodulatory effects of long -term STN-DBS. Materials & methods: In this study, adult male Sprague Dawley rats were randomly assigned to EV (Empty Vector) and A53T groups and additionally divided into 2 subgroups: stim-ON and stim-OFF. During stereotaxic injection of viral vectors (EV or human AAV-A53T-αSynuclein virus), electrophysiological recordings and DBS electrodes were implanted. To obtain the LFP and ECoG data, we conducted monopolar LFP recordings in globus pallidus - external segment (GPe) and electrocorticography (ECoG) in motor cortex during 4 recording sessions - 1, 3, 6, 8 weeks after surgery. Continuous high frequency DBS / sham-DBS was induced from the 3rd week on, lasting for additional 3 weeks. Neuromodulatory effects of long-term STN-DBS on LFP / ECoG were evaluated immediately at stimulation termination in awake, resting state animals, and repeated after wash-out period for 2 weeks. Results: Both A53T groups developed augmented beta activity in MCx and GPe vs. EV at week 3 after surgery (X 2 ≥7.33, p≤0.03; z≥-2.45, p≤0.05). In the A53T stim-ON group, 3 weeks of continuous STN-DBS suppressed the elevated MCx and GPe beta power compared to EV at week 6 (z≥-1.12, p≥0.25). Specifically, in the A53T stim-ON group, the suppressive effect of beta power after the long-term STN-DBS was still present after 2 weeks wash-out period in the GPe (z = -1.41, p = 0.16), but not in the MCx (z = -2.12, p = 0.03) compared to EV. In contrast, the A53T stim-OFF group augmented MCx and GPe beta power sustainably for 8 weeks (z≥-2.45, p≤0.05). Conclusion: Our preliminary results suggest that long-term STN-DBS has a suppressive effect on pathological beta oscillations in the progressive A53T-aSyn PD rat model.

Perspectives on the urological care in Parkinson's disease patients.

Parkinson's disease (PD) is recognized as the most common neurodegenerative disorder after Alzheimer's disease. Lower urinary tract symptoms are common in patients with PD, either storage symptoms (overactive bladder symptoms or OAB) or voiding symptoms. The most important diagnostic clues for urinary disturbances are provided by the patient's medical history. Urodynamic evaluation allows the determination of the underlying bladder disorder and may help in the treatment selection. Pharmacologic interventions especially anticholinergic medications are the first-line option for treating OAB in patients with PD. However, it is important to balance the therapeutic benefits of these drugs with their potential adverse effects. Intra-detrusor Botulinum toxin injections, electrical stimulation were also used to treat OAB in those patients with variable efficacy. Mirabegron is a β3-agonist that can also be used for OAB with superior tolerability to anticholinergics. Desmopressin is effective for the management of nocturnal polyuria which has been reported to be common in PD. Deep brain stimulation (DBS) surgery is effective in improving urinary functions in PD patients. Sexual dysfunction is also common in PD. Phosphodiesterase type 5 inhibitors are first-line therapies for PD-associated erectile dysfunction (ED). Treatment with apomorphine sublingually is another therapeutic option for PD patients with ED. Pathologic hypersexuality has occasionally been reported in patients with PD, linked to dopaminergic agonists. The first step of treatment of hypersexuality consists of reducing the dose of dopaminergic medication. This review summarizes the epidemiology, pathogenesis, risk factors, genetic, clinical manifestations, diagnostic test, and management of PD. Lastly, the urologic outcomes and therapies are reviewed.

Efficacy and Safety of Light Therapy as a Home Treatment for Motor and Non-Motor Symptoms of Parkinson Disease: A Meta-Analysis.

BackgroundNon-visual effects of the retina have been increasingly confirmed in developing Parkinson disease (PD). Light therapy (LT) has been proven to be an effective non-pharmacotherapy for improving the prognosis of PD, but the pathway of action is unclear, and there is a lack of a unified and standardized LT regimen. We aimed to evaluate the efficacy and safety of various LT measures in improving motor and non-motor symptoms in patients with idiopathic PD via a meta-analysis.Material/MethodsCENTRAL, EMBASE, CINAHL, PEDro, and PubMed were searched for randomized controlled trials (RCTs) investigating the efficacy of LT for PD. Cochrane’s Risk of bias tool and the GRADE approach were used to assess evidence quality. A meta-analysis and subgroup analyses evaluated the differences in efficacy produced by the different LT protocols. Trial sequential analysis (TSA) verified the analyses outcome and quantified the statistical relevance of the data.ResultsPatients receiving LT had significantly better scores for motor function (MD=−4.68, 95% Cl −8.25 to −1.12, P=0.01) compared with the control group exposed to dim-red light. In addition, in terms of non-motor symptoms, depression (SMD=−0.27, 95% Cl −0.52 to −0.02, P=0.04) and sleep disturbance-related scores (MD=3.45, 95% Cl 0.12 to 6.78, P=0.04) similarly showed significant optimization after receiving LT.ConclusionsThe results of this meta-analysis show strong evidence that LT has significant efficacy on motor and non-motor function in PD patients.

Dopamine depletion and subcortical dysfunction disrupt cortical synchronization and metastability affecting cognitive function in Parkinson's disease.

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large‐scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting‐state blood‐oxygen‐level‐dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical–cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia.

Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease.

Sleep disorders are one of the most common non-motor symptoms in Parkinson's disease (PD). It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. The most cited sleep disorders in PD included insomnia, restless legs syndrome (RLS), rapid eye movement (REM), sleep behavior disorders (RBD), excessive daytime sleepiness (EDS) and sleep disordered breathing (SDB), which can appear alone or several at the same time. In this review, we listed the recommended pharmacological treatments for common sleep disorders in PD, and discussed the recommended dosages, benefits and side effects of relative drugs. We also discussed non-pharmacological treatments to improve sleep quality, including sleep hygiene education, exercise, deep brain stimulation, cognitive behavior therapy and complementary therapies. We tried to find proper interventions for different types of sleep disorders in PD, while minimizing relative side effects.

The PINK1-Parkin mitophagy signalling pathway is not functional in peripheral blood mononuclear cells.

Mutations in the PINK1 and PRKN genes are the most common cause of early-onset familial Parkinson disease. These genes code for the PINK1 and Parkin proteins, respectively, which are involved in the degradation of dysfunctional mitochondria through mitophagy. An early step in PINK1 -Parkin mediated mitophagy is the ubiquitination of the mitofusin proteins MFN1 and -2. The ubiquitination of MFN1 and -2 in patient samples may therefore serve as a biomarker to determine the functional effects of PINK1 and PRKN mutations, and to screen idiopathic patients for potential mitophagy defects. We aimed to characterise the expression of the PINK1 -Parkin mitophagy machinery in peripheral blood mononuclear cells (PBMCs) and assess if these cells could serve as a platform to evaluate mitophagy via analysis of MFN1 and -2 ubiquitination. Mitophagy was induced through mitochondrial depolarisation by treatment with the protonophore CCCP and ubiquitinated MFN proteins were analysed by western blotting. In addition, PINK1 and PRKN mRNA and protein expression levels were characterised with reverse transcriptase quantitative PCR and western blotting, respectively. Whilst CCCP treatment led to MFN ubiquitination in primary fibroblasts, SH-SY5Y neuroblastoma cells and Jurkat leukaemic cells, treatment of PBMCs did not induce ubiquitination of MFN. PRKN mRNA and protein was readily detectable in PBMCs at comparable levels to those observed in Jurkat and fibroblast cells. In contrast, PINK1 protein was undetectable and PINK1 mRNA levels were remarkably low in control PBMCs. Our findings suggest that the PINK1 -Parkin mitophagy signalling pathway is not functional in PBMCs. Therefore, PBMCs are not a suitable biosample for analysis of mitophagy function in Parkinson disease patients.

Increased activation of the caudate nucleus and parahippocampal gyrus in Parkinson's disease patients with dysphagia after repetitive transcranial magnetic stimulation: a case-control study.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively improve impaired swallowing in Parkinson's disease (PD) patients with dysphagia. However, little is known about how rTMS affects the corresponding brain regions in this patient group. In this case-control study, we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy, Capital Medical University. The patients received high-frequency rTMS of the motor cortex once per day for 10 successive days. Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls. The results revealed that before treatment, PD patients with dysphagia showed greater activation in the precentral gyrus, supplementary motor area, and cerebellum compared with healthy controls, and this enhanced activation was weakened after treatment. Furthermore, before treatment, PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus, caudate nucleus, and left thalamus compared with healthy controls, and this activation increased after treatment. In addition, PD patients with dysphagia reported improved subjective swallowing sensations after rTMS. These findings suggest that swallowing function in PD patients with dysphagia improved after rTMS of the motor cortex. This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus. The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University (approval No. 2018bkky017) on March 6, 2018 and was registered with Chinese Clinical Trial Registry (registration No. ChiCTR 1800017207) on July 18, 2018.