Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease:a phaseⅠ/Ⅱclinical trial

Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure AD.Aims The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and 48.Results No adverse events were reported.In the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive function.Moreover,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36.There were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.

Ketogenic diet alleviates cognitive dysfunction and neuroinflammation in APP/PS1 mice via the Nrf2/HO-1 and NF-κB signaling pathways

Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractory epilepsy,has recently been proposed as a potential treatment for a variety of neurological diseases,including Alzheimer's disease.However,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains unclear.The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer's disease.Male amyloid precursor protein/presenilin 1(APP/PS1)mice were randomly assigned to either a ketogenic diet or control diet group,and received their respective diets for a duration of 3 months.The findings show that ketogenic diet administration enhanced cognitive function,attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice,and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway.Collectively,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation.This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.

Parkinson’s disease in China:a forty-year growing track of bedside work

The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications.From the view of clinical research,we also discuss the current status of clinical trials,diagnostic biomarkers,treatment of Parkinson’s disease,tertiary network and post-occupation education in Chinese Parkinson’s disease clinics.

The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease

Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Background Freezing of gait(FOG)is a common,disabling symptom of Parkinson’s disease(PD),but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers.The main focus of this review is to summarize the possible mechanisms underlying FOG,the risk factors for screening and predicting the onset of FOG,and the clinical trials involving various therapeutic strategies.In addition,the limitations and recommendations for future research design are also discussed.Main body In the mechanism section,we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG.In the risk factor section,gait disorders,PIGD phenotype,lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence.In the treatment section,we summarized the clinical trials of pharmacological and non-pharmacological treatments.Despite the limited effectiveness of current medications for FOG,especially levodopa resistant FOG,there were some drugs that showed promise such as istradefylline and rasagiline.Non-pharmacological treatments encompass invasive brain and spinal cord stimulation,noninvasive repetitive transcranial magnetic stimulation(rTMS)or transcranial direct current stimulation(tDCS)and vagus nerve stimulation(VNS),and physiotherapeutic approaches including cues and other training strategies.Several novel therapeutic strategies seem to be effective,such as rTMS over supplementary motor area(SMA),dual-site DBS,spinal cord stimulation(SCS)and VNS.Of physiotherapy,wearable cueing devices seem to be generally effective and promising.Conclusion FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration.Several risk factors of FOG have been identified,but need combinatorial optimization for predicting FOG more precisely.Although firm conclusions cannot be drawn on therapeutic efficacy,the literature suggested that some therapeutic strategies showed promise.

Salidroside reduces tau hyperphosphorylation via up-regulating GSK-3β phosphorylation in a tau transgenic Drosophila model of Alzheimer’s disease

Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment against AD.Salidroside(Sal)is the main effective component of Rhodiola rosea L.,which has several pharmacological activities.The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms.Methods:We used tau transgenic Drosophila line(TAU)in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system.After feeding flies with Sal,the lifespan and locomotor activity were recorded.We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry,and detected the levels of total glycogen synthase kinase 3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),t-tau and p-tau in the brain by western blot analysis.Results:Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity.We also observed less vacuoles in the mushroom body,upregulated level of p-GSK-3βand downregulated p-tau following Sal treatment.Conclusion:Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss.The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3βand down-regulation of the p-tau.

Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets

Microglia activation is observed in various neurodegenerative diseases.Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity.Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions.

Hemiballism-hemichorea induced by ketotic hyperglycemia: case report with PET study and review of the literature

Hemiballism-hemichorea(HB-HC)is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients.Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones.We described the computed tomography and magnetic resonance imaging findings in these two patients,which is similar to that of non-ketotic hyperglycemic HB-HC patients.FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other.We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages.

Efficacy and safety of rasagiline in Chinese patients with early Parkinson’s disease:a randomized, double-blind,parallel,placebo-controlled,fixed-dose study

Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is unclear.This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD.Methods:A 26-weeks,randomized,double-blind,placebo-controlled study has been performed at 15 sites in China and enrolled outpatients(≥35 years old)with idiopathic PD without a history of using any dopaminergic drugs.Participants were randomized 1:1 to receive rasagiline 1 mg once daily or placebo.The primary endpoint was the change of the Unified Parkinson’s Disease Rating Scale(UPDRS)total score from baseline to 26 weeks treatment.Secondary endpoints included changes in UPDRS subscale scores from part Ⅰ to Ⅲ.Health status was assessed with the PD Questionnaire(PDQ)-39 and EuroQol-Five-Dimension(EQ-5D)questionnaire.Safety profile was collected until 30 weeks after randomization.Results:A total of 130 patients(n=65/group)were recruited,and 127(rasagiline,n=64;placebo,n=63)were included in the full analysis set.Baseline characteristics were comparable between the two groups.The decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group(−3.18±0.95 vs.−0.18±0.98,P=0.025),and the mean UPDRS part I non-motor symptoms score(−0.54±0.15 vs.-0.08±0.15,P=0.003)were significantly decreased in the rasagiline group compared with placebo treated patients.An improvement trend was observed in the active treatment group for the subscales evaluation with parts Ⅱ and Ⅲ,while the difference to placebo was not statistically significant.Life quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated patients.The overall incidence of treatment-emergent adverse events(AEs)was slightly lower in the rasagiline group(41.5%)than in the placebo group(46.2%).Conclusions:Rasagiline is effective,safe,and well tolerated as monotherapy for the treatment of Chinese PD patients.

Recommendations for the diagnosis and treatment of paroxysmal kinesigemc dyskinesia: an expert consensus in China

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals.

Chinese expert consensus on programming deep brain stimulation for patients with Parkinson’s disease

Background:Deep Brain Stimulation(DBS)therapy for the treatment of Parkinson’s Disease(PD)is now a well-established option for some patients.Postoperative standardized programming processes can improve the level of postoperative management and programming,relieve symptoms and improve quality of life.Main body:In order to improve the quality of the programming,the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China.Conclusion:This Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD.

Objective assessment of bradykinesia in Parkinson’s disease using evolutionary algorithms:clinical validation

Background:There is an urgent need for developing objective,effective and convenient measurements to help clinicians accurately identify bradykinesia.The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping(FT)that uses evolutionary algorithms(EAs)and explore whether it can be used to identify early stage Parkinson’s disease(PD).Methods:One hundred and seven PD,41 essential tremor(ET)patients and 49 normal controls(NC)were recruited.Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger.Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs.The output from the device(referred to as"PD-Monitor")scaled from−1 to+1(where higher scores indicate greater severity of bradykinesia).Meanwhile,the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale(MDS-UPDRS)FT item.Results:With an increasing MDS-UPDRS FT score,the PD-Monitor score from the same hand side increased correspondingly.PD-Monitor score correlated well with MDS-UPDRS FT score(right side:r=0.819,P=0.000;left side:r=0.783,P=0.000).Moreover,PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup(FT bradykinesia scored from 1 to 3)were all higher than that in NC.Receiver operating characteristic(ROC)curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy(≥89.7%)in the right dominant hand.Furthermore,PD-Monitor scores could discriminate early stage PD from NC,with area under the ROC curve greater than or equal to 0.899.Additionally,ET without bradykinesia could be differentiated from PD by PD-Monitor scores.A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides.Conclusions:Our study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD,but also had the potential to differentiate early stage PD from normality.

Gut microbiome,cognitive function and brain structure:a multi-omics integration analysis

Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.Methods:We included 1430 participants from the Guangzhou Nutrition and Health Study(GNHS)with both gut microbiome and cognitive assessment data available as a discovery cohort,of whom 272 individuals provided fecal samples twice before cognitive assessment.We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit.Fecal 16S rRNA and shotgun metagenomic sequencing,tar-geted serum metabolomics,and cytokine measurements were performed in the GNHS.The validation analyses were conducted in an Alzheimer’s disease case-control study(replication study 1,n=90)and another community-based cohort(replication study 2,n=1300)with cross-sectional dataset.Results:We found protective associations of specific gut microbial genera(Odoribacter,Butyricimonas,and Bac-teroides)with cognitive impairment in both the discovery cohort and the replication study 1.Result of Bacteroides was further validated in the replication study 2.Odoribacter was positively associated with hippocampal volume(β,0.16;95%CI 0.06-0.26,P=0.002),which might be mediated by acetic acids.Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment.We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Conclusions:Our findings reveal that specific gut microbial features are closely associated with cognitive impair-ment and decreased hippocampal volume,which may play an important role in dementia development.

Subthalamic nucleus deep brain stimulation for Parkinson’s disease: 8 years of follow-up

Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.

The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study

Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.

Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice

Background Neuropsychiatric symptoms(NPS)such as depression,anxiety,apathy,and irritability occur in prodromal phases of clinical Alzheimer’s disease(AD),which might be an increased risk for later developing AD.Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor(SSRI)paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress,we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age.Next,we tested the cognitive,biochemical and pathological,effects of long term administration of paroxetine at 6 months old.Results Our results showed that AD mice displayed emotional dysfunction in the early stage.Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice.Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice.These neuroprotective effects are attributable to functional restoration of glutamate receptor(GluN2A)in AD mice.

Functional Connectivity-Based Modelling Simulates SubjectSpecific Network Spreading Effects of Focal Brain Stimulation

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity(up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity(Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy,and warrant future experimental investigation to validate its clinical utility.

A perspective on therapies for amyotrophic lateral sclerosis:can disease progression be curbed?

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease involving both upper and lower motor neurons,leading to paralysis and eventually death.Symptomatic treatments such as inhibition of salivation,alleviation of muscle cramps,and relief of spasticity and pain still play an important role in enhancing the quality of life.To date,riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries.While there is adequate consensus on the modest efficacy of riluzole,there are still open questions concerning the efficacy of edaravone in slowing the disease progression.Therefore,identification of novel therapeutic strategies is urgently needed.Impaired autophagic process plays a critical role in ALS pathogenesis.In this review,we focus on therapies modulating autophagy in the context of ALS.Furthermore,stem cell therapies,gene therapies,and newly-developed biomaterials have great potentials in alleviating neurodegeneration,which might halt the disease progression.In this review,we will summarize the current and prospective therapies for ALS.

The predictive value of SS-16 in clinically diagnosed Parkinson’s disease patients:comparison with ^(99m)Tc-TRODAT-1 SPECT scans

Background:Dopamine transporter based imaging has high diagnostic performance in distinguishing patients with Parkinson’s disease(PD)from patients with non-Parkinsonian syndromes.Our previous study indicated that the“Sniffin’Sticks”odor identification test(SS-16)acts as a valid instrument for olfactory assessment in Chinese PD patients.The aim of the study was to compare the efficacy of the two methods in diagnosing PD.Methods:Fifty-two PD patients were involved in this study and underwent single photon emission computed tomography(SPECT)imaging using the labeled dopamine transporter radiotracer ^(99)mTc-TRODAT-1 to assess nigrostriatal dopaminergic function.Olfactory function was assessed with the“Sniffin’Sticks”odor identification test(SS-16)in all patients who received DAT-SPECT scanning.Statistical analysis(SPSS version 21)was carried out to determine the diagnostic accuracy of SS-16 as well as its correlation with ^(99)mTc-TRODAT-1 SPECT,its positive predictive value(PPV),and negative predictive value(NPV).Results:We identified a negative correlation between SS-16 and DAT SPECT(Kappa=0.269,p=0.004).By using the ^(99)mTc-TRODAT-1 uptake results as the gold standard,the sensitivity and specificity of SS-16 was 56.8 and 37.5%,respectively.Furthermore,the negative and positive predictive values were calculated as 13.6 and 83.3%,respectively.Conclusions:SS-16 would not be used as a diagnostic tool for early stage PD patients.Negative results of SS-16 would not exclude the diagnosis of PD.Further tests are needed for validation.

Clinical management and associated costs for moderate and severe Alzheimer’s disease in urban China: a Delphi panel study

Background:Healthcare resource utilisation for Alzheimer’s disease(AD)in China is not well understood.This Delphi panel study aimed to describe the clinical management pathways for moderate and severe AD patients in urban China and to define the amount and cost of healthcare resources used.Methods:A panel of 11 experts was recruited from urban China to participate in two rounds of preparatory interviews.In the first round,9 physicians specialised in dementia gave a qualitative description of the clinical management of AD patients.In the second round,2 hospital administrators were asked about the cost of AD management and care.Results from the interviews were discussed by the experts in a Delphi panel meeting,where consensus was reached on quantitative aspects of AD management,including the rate of healthcare resource utilisation,the respective unit costs and caregiving time.Results:Interviewees reported that mild AD is under-recognised in China;most patients are diagnosed with moderate to severe AD.Loss of independence and agitation/aggression are the main drivers for healthcare resource utilisation and contribute to a heavier caregiver burden.It was estimated that 70%moderate AD patients are independent/non-aggressive at the time of diagnosis,15%are independent/aggressive,10%are dependent/non-aggressive,and 5%are dependent/aggressive.Dependent/aggressive AD patients are more likely to be hospitalised(70–90%)than accepted in a nursing home(0–20%),while the opposite is true for dependent/non-aggressive patients(5–35%for hospitalisation vs.80%for nursing home).Independent AD patients require 1–3 hours/day of caregiver time,while dependent patients can require up to 12–15 hours/day.Experts agreed that AD complicates the management of age-related comorbidities,found in 70–80%of all AD patients,increasing the frequency and cost of hospitalisation.Conclusions:The Delphi panel approach was an efficient method of gathering data about the amount of healthcare resources used and associated costs for moderate and severe AD patients in urban China.The results of this study provide a useful source of information for decision makers to improve future healthcare policies and resource planning,as well as to perform economic evaluations of AD therapies.