Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.

Clinical features and relative factors of constipation in a cohort of Chinese patients with Parkinson's disease

BACKGROUND Constipation as a most common non-motor symptom of Parkinson's disease(PD),has a higher prevalence compared to the general population.The etiologies of constipation in PD are diverse.In addition to physical weakness and other factors of disease,the lifestyles and eating habits are also important factors.Therefore,the prevalence and influencing factors of constipation may vary among different populations.AIM To determine the prevalence of constipation and analyze relative factors in a cohort of Chinese patients with PD.METHODS All the patients diagnosed with PD according to the movement disorders society criteria were consecutively collected by a self-developed questionnaire.Rome III diagnostic criteria were used to assess functional constipation and Wexner score was used to estimate the severity of constipation.Non-motor symptoms(NMS)were assessed with the non-motor symptoms assessment scale(NMSS).Unified Parkinson's disease Rating Scale III(UPDRS III)was used to evaluate the severity of motor symptoms.The modified Hoehn-Yahr stage was used to evaluate the severity of PD.Cognitive function was assessed using Montreal cognitive assessment(MoCA).Depression and anxiety were rated with the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA).Quality of life was assessed using the Parkinson’s disease Questionnaire-39 items(PDQ-39).RESULTS Of 166 patients enrolled,87(52.41%)were accompanied with constipation,and 30(34.48%)experienced constipation for 6.30±5.06 years before motor symptoms occurred.Age,Hoehn-Yahr stage,disease duration,levodopa medication times,incidence of motor complications,the scores of UPDRS total,UPDRS III,NMSS,HAMD,HAMA,and PDQ-39 in the constipation group were higher than those in the non-constipation group(P<0.05),but there was no difference in the scores of MoCA,clinical types,or medications between the two groups(P>0.05).There was a higher incidence of depression in patients with constipation(P<0.05),but there were no difference in the incidence of anxiety and cognitive impairment between the two groups(P>0.05).As Hoehn-Yahr stages increased,the severity of constipation increased(P<0.05),but not the incidence of constipation(P>0.05).Pearson correlation analysis showed that constipation was moderately positively correlated with age,Hoehn-Yahr stage,and scores of NMSS,UPDRS III,UPDRS total,PDQ-39,HAMD,and HAMA(r=0.255,0.172,0.361,0.194,0.221,0.237,0.238,and 0.207,P<0.05).Logistic regression analysis showed that only NMSS score was an independent risk factor for constipation(P<0.001).CONCLUSION Our findings confirm that constipation has a relatively high frequency in patients with PD.PD patients with constipation have a higher incidence of depression,which leads to worse quality of life.

Study of an integrated non-motor symptoms questionnaire for Parkinson＇s disease

Background Although the validity of non-motor symptoms screening questionnaire （NMSQuest） for Parkinson＇s disease has been verified in several recent researches, the specificity of the questionnaire is still in doubt. This study aimed to compare the non-motor symptoms （NMS） in Parkinson＇s disease （PD） with a medically ill control group. Methods In this study, the first comprehensive clinic-based NMS screening questionnaire for PD developed by the Parkinson＇s Disease Non-Motor Group （PDNMG） was used. Data from 90 PD patients and 270 sex-and age-matched control subjects, including stroke （n=90）, heart disease （n=-90） and diabetes （n=-90） were analyzed. Results Compared with control group, NMS was more common in PD; on an average, most PD patients reported more than 12 non-motor items. There was a correlation of total NMS score in PD patients with Hoehn ＆ Yahr Staging, but not with age, sex distribution, disease duration, or age at disease onset. Additionally, depression, constipation and impaired olfaction which occurred prior to the motor symptoms of PD were reported in this study. Conclusions NMS are more common in PD patients. There are some NMS that occurred at the preclinical stage of PD and might predict the onset of motor symptoms of PD patients.

Effects of a Cocktail Supplement of Ginkgo Biloba and Acai Extract on Cognitive Symptoms of Parkinson’s Disease

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects and potential for dependency. This study investigates the effects of a natural supplement combination of Ginkgo Biloba and Acai Extract on cognitive symptoms in a 77-year-old male with PD. The participant underwent a three-month supplementation regimen, with cognitive function assessed using the Montreal Cognitive Assessment (MoCA) test before and after the intervention. The results indicated an improvement in cognitive scores, suggesting that the combination of Ginkgo Biloba and Acai Extract may offer a promising alternative or adjunct to conventional PD treatments. This study highlights the potential of natural supplements in managing PD symptoms and calls for further research with larger sample sizes to confirm these findings. Human data was performed in accordance with the Declaration of Helsinki by the Roxbury District IRB Board (IRB Number: IRB00011767).

Liquid Subcutaneous Levodopa-Carbidopa ND0612 Effects on Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson＇s Disease

Objective： This review examines the evidence that deep brain stimulation （DBS） has extensive impact on nonmotor symptoms （NMSs） of patients with Parkinson＇s disease （PD）. Data Sources： We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus （GPi）, subthalamic nucleus （STN）, and ventral intermediate thalamic nucleus. Study Selection： We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs： Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups： those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results： In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS： The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions： As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

Non-motor signs and symptoms in Parkinson’s disease

Motor symptoms are cardinal clinical features of Parkinson’s disease (PD). Progress in drug therapy and rehabilitation has been presenting beneficial effect for motor symptoms. However, non-motor symptoms and signs in PD have been accumulated growing attentions and its amelioration may also give beneficial effect for PD patients’ and their care givers’ quality of life. In this mini-review, I overviewed non-motor symptoms and signs in PD.

Non-Motor Symptoms in Parkinson’s Disease Patients—An Observational Study

Background: Parkinson’s disease (PD) remains a challenge for neurologists, particularly in its advanced stages when non-motor symptoms become a burden for the patient. While motor symptoms may be satisfactorily controlled with levodopa therapy or continuous levodopa/carbidopa intestinal gel (LCIG) administration, autonomic, sleep and mental disorders are hard to treat. During the last years, researchers have shifted their interest more to non-motor symptoms, PD being now considered a complex multiorgan impairment. Objective: The aim of this study was to describe non-motor symptoms in 40 Romanian patients diagnosed with PD, under conventional and LCIG administration treatment. Methods: A cross-sectional observational study was conducted, consisting of two groups of 20 patients each: the first group comprised PD patients who received conventional Levodopa treatment, while the second group was formed of patients receiving LCIG therapy. Various data concerning patient’s age, gender, duration of illness, comorbidities, motor and non-motor symptoms were recorded. The data were processed in SPSS v.20. Results: Subjects under continuous LCIG administration, although showing amelioration of motor symptoms, complained more frequently of constipation, mental, and sleeping disorders (statistically significant). Regarding anosmia, orthostatic hypotension, hypersalivation, urinary incontinence and restless legs syndrome, no statistical significant difference was observed between the two groups (p > 0.05). Conclusion: Nowadays, more research is conducted on non-motor symptoms in PD patients, as therapeutic measures try to limit these burdens, in order to improve patient’s quality of life.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Delusional parasitosis as premotor symptom of parkinson's disease:A case report

BACKGROUND Delusional parasitosis is characterized by a false belief of being infested with parasites,insects,or worms.This illness is observed in patients with Parkinson’s disease and is usually related to dopaminergic treatment.To our knowledge,no cases of delusional parasitosis have been reported as a premotor symptom or nonmotor symptom of Parkinson’s disease.CASE SUMMARY A 75-year-old woman presented with a complaint of itching that she ascribed to the presence of insects in her skin,and she had erythematous plaques on her trunk,arms,buttocks,and face.These symptoms started two months before the visit to the hospital.She took medication,including antipsychotics,with a diagnosis of delusional parasitosis,and the delusion improved after three months.A year later,antipsychotics were discontinued,and anxiety and depression were controlled with medication.However,she complained of bradykinesia,masked face,hand tremor,and mild rigidity,and we performed fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane positron emission tomography(PET),which showed mildly decreased DAT binding in the right anterior putamen and caudate nucleus.Parkinson’s disease was diagnosed on the basis of PET and clinical symptoms.CONCLUSION In conclusion,delusional parasitosis can be considered a non-motor sign of Parkinson’s disease along with depression,anxiety,and constipation.

Voltage adjustment improves rigidity and tremor in Parkinson's disease patients receiving deep brain stimulation

Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is consid- ered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson＇s disease （four men and two women, aged 37-65 years）, who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson＇s Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 ps and frequency at 130 Hz. Voltage adjust- ment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov （identifier： NCT01934881）.

The Effects of Exercise on People with Parkinson’s Disease—Review

Quality of life encompasses physical, psychological and social aspects of health. Apart from motor symptoms (physical aspects), Parkinson’s disease (PD) is also closely related with various non-motor symptoms (psychological and social aspects) that can undermine quality of life greatly, even in early stages of the disease. Most research studies in this field focus on analysis of motor symptoms in PD sufferers. Although benefits of physical activity for the psychosocial quality of life are well-known, they have been mostly neglected in case of the people suffering from PD. Numerous studies clearly show that training programs can ameliorate the quality of life as far as non-motor functions in PD sufferers are concerned. The only psychological aspects of the disease related to the effects of exercise that have been researched so far are depression and cognitive functions. Depression is the most common denominator of poor quality of life, while dementia often accompanies the Parkinson’s disease. Studies have shown positive effects of exercise on the social life of those suffering from the disease, especially in case of group exercise. Studying psychological and social aspects of such chronic conditions as PD is of utmost importance for monitoring the patient’s adjustment to the disease, functioning with it, as well as the overall well-being and satisfaction with life. Thus far, the results have been pointing towards improvement of the quality of life. Exercise is a readily available method of treatment in case of PD, especially if applied in the early stages of the disease. In addition to reviewing the existing studies on the relation between exercise and quality of life of the patients, this paper will also focus on the way the psychological and social aspects of PD are influenced by exercise.

Magnetic resonance morphometry of the loss of gray matter volume in Parkinson's disease patients

Voxel-based morphometry can be used to quantitatively compare structural differences and func-tional changes of gray matter in subjects. In the present study, we compared gray matter images of 32 patients with Parkinson’s disease and 25 healthy controls using voxel-based morphometry based on 3.0 T high-field magnetic resonance T1-weighted imaging and clinical neurological scale scores. Results showed that the scores in Mini-Mental State Examination and Montreal Cognitive Assessment were lower in patients compared with controls. In particular, the scores of visuospatial/executive function items in Montreal Cognitive Assessment were significantly reduced, but mean scores of non-motor symptoms significantly increased, in patients with Parkinson’s dis-ease. In addition, gray matter volume was significantly diminished in Parkinson’s disease patients compared with normal controls, including bilateral temporal lobe, bilateral occipital lobe, bilateral parietal lobe, bilateral frontal lobe, bilateral insular lobe, bilateral parahippocampal gyrus, bilateral amygdale, right uncus, and right posterior lobe of the cerebel um. These findings indicate that voxel-based morphometry can accurately and quantitatively assess the loss of gray matter volume in patients with Parkinson＇s disease, and provide essential neuroimaging evidence for multisystem pathological mechanisms involved in Parkinson’s disease.

Effects of Physical Activity Levels on Fatigue Perception in Patients with Parkinson’s Disease and Neurologically Healthy Individuals

Background: Recent researches involving fatigue and Parkinson’s disease (PD) sought to verify its incidence and the impacts of fatigue on quality life of patients with PD. Despite the importance of regular physical activity practice, there are only few studies that verified the influence of the levels of physical activity on fatigue in patients with PD. Objective: The aim of this study was to compare perception of fatigue between individuals with PD and neurologically healthy individuals (control group), considering the physical activity levels;and to verify the relation between physical activity levels and fatigue dimensions for individuals with PD and control group. Methods: Eighty individuals (40 patients with PD and 40 control individuals) participated in this study. Physical activity levels were evaluated through Modified Baecke Questionnaire for Older Adults. Multidimensional Fatigue Inventory (MFI) was used in order to evaluate fatigue dimensions (general, physical and mental fatigue, reduced motivation and activity). MANOVA two-way and Pearson linear correlation test were performed to analyze the data. Results: Patients with PD presented higher levels of fatigue, in all dimensions evaluated by MFI, comparing to control individuals. There was no association between physical activity levels and perception of fatigue for patients with PD and control individuals. Conclusion: Patients with PD showed increased perception of fatigue when compared to control individuals, due to PD characteristics. In addition, the perception of fatigue’s symptom was not influenced and had no relation by the level of physical activity.

Safety and Efficacy of a Transdermal Rotigotine for the Treatment of Fatigue and Quality of Life in Patients with Parkinson’s Disease

Aim: To evaluate safety and efficacy of a transdermal rotigotine for the treatment of fatigue and quality of life (QOL) in patients with Parkinson’s disease (PD). This was a multi-sites open-label study of 58 PD patients (male 26, female 32) who met a Japanese PD diagnosis criterion. They received a transdermal rotigotine 4.5 mg/day for 8 weeks. We added a rotigotine on the previous anti-Parkinson’s drugs. Clinical signs were evaluated by Hoehn-Yahr (H-Y) stage, unified Parkinson’s disease rating scale (UPDRS), fatigue severity scale (FSS), and Euro quality of life (QOL). The scores of UPDRS improved from 35.2 ± 8.0 (mean ± SD) to 31.8 ± 8.3 (P = 0.14). There was no significant improvement or worsening of the H-Y stages. The scores of FSS improved from 57.3 ± 12.7 (mean ± SD) to 50.1 ± 11.8 (P = 0.061). The scores of QOL improved from 38.1 ± 11.1 to 48.3 ± 10.0 (P = 0.068). Our data demonstrate that, in a small sample size, administration of a transdermal rotigotine was associated with few side effects and was modestly effective for the treatment of fatigue and QOL in patients with PD.

Effects of Cholinesterase Inhibitors in Cognition on Parkinson’s Disease Dementia: A Systematic Review and Meta-Analysis

Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.

Effectiveness of Istradefylline for Fatigue and Quality of Life in Parkinson’s Disease Patients’ and of Their Caregivers’

Objectives: We evaluated efficacy and safety of istradefylline that is the first selective adenosine A2A receptor antagonist, for the treatment of non-motor symptoms and quality of life (QoL) in Parkinson’s disease (PD) patients with and QoL in their caregivers. Methods: This was a multisites study of 40 PD patients (female 24, male 16) who fully filled UK PD society brain bank clinical diagnostic criteria. They received istradefylline 20 mg/day for 8 weeks. We added istradefylline on the previous anti-Parkinson’s drugs. Clinical severities were evaluated by Hoehn-Yahr (H-Y) stage, unified PD rating scale (UPDRS), non-motor symptoms in PD (NMSPD), fatigue severity scale (FSS) and Euro QoL. Also, we evaluated their caregiver’s QoL by Euro QoL. Results: The scores of UPDRS part I improved from 1.3 ± 1.1 to 06 ± 0.9 (P = 0.18), part II improved from 11.9 ± 3.2 to 11.0 ± 3.1 (P = 0.17), part III improved from 34.8 ± 7.2 to 32.1 ± 8.3 (P = 0.105). There was no significant improvement or worsening of the H-Y stages. The scores of NMSPD improved from 49.9 ± 11.2 to 43.9 ± 10.6 (P = 0.08). The scores of FSS improved from 62.8 ± 7.1 to 52.3 ± 9.3 (P = 0.049). The total scores of Euro QoL in PD patients improved from 48.8 ± 14.9 to 57.2 ± 13.0 (P = 0.045). The total scores of Euro QoL in patients’ caregivers improved from 54.2 ± 11.0 to 59.8 ± 10.9 (P = 0.046). Conclusions: Our data demonstrated that istradefylline was associated with few side effects and was modestly effective for the treatment of non-motor symptoms especially fatigue that might improve QoL in PD patients as well as in their caregivers’.

Parkinson’s disease: how should we consider the selectivity and progressivity of its neuropathology?

Parkinson’s disease(PD)is a common age-related neurodegenerative disease characterized by movement disorders.The hallmark pathological lesions of PD are the formation of Lewy pathology in selected populations of neurons throughout the nervous system.Braak and his colleagues created a staging system for PD describing the connection between Lewy pathology and disease severity.They proposed that Lewy pathology might be initially triggered by exogenous pathogens targeting the enteric or olfactory nervous system,then spread in a prion-like propagation manner from the peripheral nerves to the lower brainstem and midbrain,before finally reaching higher cortical structures,causing a sequential occurrence of the non-motor and motor symptoms,depending on the lesioned neurons.However,emerging evidence also supports a functional threshold hypothesis proposed by Engelender and Isacson in which Lewy pathology may occur parallelly in the central and peripheral nervous systems and the symptoms only begin when the functional reserve of the affected neurons(and their connecting brain regions)is unable to allow for network compensation.Consequently,early symptoms of PD reflect the loss of function in the least compensated systems,such as the enteric and olfactory nervous systems,rather than the spread of Lewy pathology from the peripheral to the central nervous systems.The current review article provides a comprehensive overview of the evidence supporting a merged mechanism that the neurodegeneration in PD happens to those neurons that are not only intrinsically vulnerable but also affected by the spread of Lewy pathology.

Sleep Disturbance in Parkinson’s Disease Varies with Age of Onset and Family History

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.

Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China

Background:Studies suggest seasonal fluctuations of symptoms in Parkinson’s disease(PD)patients in Western countries.However,the association between seasonal change and variation in nonmotor symptoms(NMS)in Chinese PD patients is unclear.Here,we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China.Methods:We studied 1005 PD patients between April 2008 and October 2020.Patients were classified into four seasons according to the 24 Chinese solar terms,based on assessment date.We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity.Results:Among the 1005 patients studied,the mean age was 64.2±9.7 years and 569(56.6%)of them were men.Relative to the summer group,patients assessed during winter had higher Scales for Outcomes in Parkinson’s disease-Autonomic Dysfunction(SCOPA-AUT)scores(P=0.045).The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer(P=0.009).Among patients who completed polysomnography during the same period(n=135),compared with summer follow-ups,we observed a higher percentage of NREMS1 in winter and spring follow-ups(P=0.042,P=0.011),a higher NREMS1 time in spring follow-ups(P=0.0024),a lower NREMS2 time in winter follow-ups(P=0.007),and a higher percentage of phasic rapid eye movement(REM)-sleep without atonia in autumn and winter follow-ups(P=0.026 and P=0.020,respectively).In a subset of patients with PD and REM sleep behavior disorder(RBD;n=182),those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1(dream-related sub-score)than those visited during summer(P=0.034,P=0.020).We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis.Conclusions:PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter,and less sleep disturbance than those in spring and winter,suggesting that seasonal change and NMS fluctuation are related,especially in patients with early stage PD.