Study on performance comparison between Brain Health System's clinic digital memory assessment and previously used assessments in dementia risk screening / 中华老年医学杂志

Objective:To study on performance comparison between clinic digital memory assessment and previously used assessments in dementia risk screening.To compare the performance comparison between Beijing Aging Brain Rejuvenation Initiative(BABRI)Brain Health System's Clinic Digital Memory Detection as study and Alzheimer Disease-8(AD8)and the Brief Community Screening Instrument for Dementia(BCSID)as controls, We calculated and evaluated the accuracy, sensitivity and specificity of screening Mild cognitive impairment(MCI)among these tests.Furthermore, BABRI Brain Health System was used to conduct a large sample brain health examination and early dementia screening to test the validity, adaptability and stability of the evaluation results by BABRI Brain Health System'Clinic Digital Memory Detection.Methods:Dataset 1 contained 669 elderly subjects from five communities in Beijing were recruited according to inclusion and exclusion standard.The diagnosis of MCI was based on the full set of neuropsychological scale and Petersen standard.Dataset 1 was used to compare the discriminant effect of BABRI Brain Health System'Clinic Digital Memory Detection as study versus AD8 and BCSID as controls.The sensitivity, specificity, positive predictive value, negative predictive value and Youden index of each measurement tool were calculated.Then, the receiver operator characteristic(ROC)curve was prepared to compare the discrimination ability of MCI between each measurement tool.While the area under the curve(AUC)of different tools was compared by Wald χ2 test.Dataset 2 contained 284 103 subjects from 16 communities in Beijing, which were used to test the applicability of large sample screening in BABRI Brain Health System. Results:77 patients with MCI were found among 666 people, and incidence rate was 11.56% using the full set of neuropsychological scales in dataset 1.Compared with the results of other tests, the sensitivity of BABRI Brain Health System to correctly distinguish MCI was 0.753, which was close to BCSID, and better than AD8.In addition, BABRI Brain Health System's Youden's index was 0.741 and AUC was 0.905, which suggested that the specificity, positive predictive value, negative predictive value and cognitive domain coverage of MCI screening were generally better in BABRI Brain Health System than in AD8 and BCSID.Finally, the Brain Health Examination results of 284, 000 people in dataset 2 showed that the high-risk detection rate of MCI(8.65%)of the tool for people over 50 years old under a large sample was quite close to the results of dataset 1(8.67%), indicating that the BABRI Brain Health System had high stability.Conclusions:BABRI Brain Health System has not only high sensitivity and specificity, but also wide cognitive field coverage and high stability.BABRI Brain Health System is suitable for large-scale brain health examination and dementia risk screening in grass-roots communities, and is worthy of popularization.

Application of comprehensive cognitive intervention in patients with Alzheimer's disease / 中华老年医学杂志

Alzheimer's disease is the most common cause of dementia.Current treatment options for Alzheimer's disease are very limited, and non-drug treatment is receiving more and more attention.Cognitive intervention is a relatively new non-drug treatment for Alzheimer's disease.A large number of previous studies have confirmed that cognitive intervention can prevent and mitigate clinical symptoms of Alzheimer's disease.In this review, we systematically introduce cognitive intervention as a prevention tool for Alzheimer's disease and its ability to alleviate clinical symptoms of the disease, and put forward suggestions for the future application of cognitive intervention in Alzheimer's disease.

Clinical and genetic phenotypes of an autosomal recessive spinocerebellar ataxia-10 patient due to ANO10 gene mutations / 中华神经科杂志

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10 (SCAR10).Methods:A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected. Friedreich ataxia and other causes of acquired ataxia were excluded, then probands were detected by whole-exome sequencing (WES), and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members. Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results:A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES. The 40-year-old male proband of this pedigree carried compound heterozygous mutations: c.1219-2A>C and c.1163-2A>G of the ANO10 gene, both of which were novel mutations, and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents. Bioinformatic analysis predicted these two mutations were pathogenic. The proband exhibited progressive unsteady walk, dysarthria, mild cognitive impairment. His plasma total coenzyme Q 10 was decreased (0.76 μg/ml). Brain magnetic resonance imaging showed remarkable cerebellar atrophy. Conclusions:Through WES, a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified, which is rare in China. The main clinical manifestation was progressive cerebellar ataxia and cognitive decline, and brain image showed remarkable cerebellar atrophy.

Clinical and genetic phenotypes of a patient with POLR3B gene-related hypomyelinating leukodystrophy and hypogonadism / 中华神经科杂志

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of POLR3B gene related autosomal recessive cerebellar ataxia with hypogonadism.Methods:A female proband from a Chinese non-consanguineous family was admitted to Department of Neurology, China-Japan Friendship Hospital in March 2016, performed detailed physical and auxiliary examinations and excluded acquired causes of cerebellar ataxia. Genomic DNA was extracted from peripheral blood of the proband and conducted whole exome sequencing (WES) and verified in her asymptomatic parents. Potential pathogenic variants were validated by Sanger sequencing.Results:The proband exhibited progressive unsteady walk, cognitive impairment, dysarthria and dysphagia, dystonia, congenital cataract, hypogonadism as well as delayed puberty, amenorrhea and short stature and was effectively treated by hormone therapy. Magnetic resonance imaging of her brain showed diffused hypomyelination of white matter, relatively sparing the thalamus, globus pallidus, and optic radiations, as well as cerebellar atrophy and thin corpus callosum. X ray of her chest revealed thoraco-lumbar scoliosis. WES identified compound heterozygous mutations c.479A>C (p. E160A) and c.2657G>C (p.R886T) of POLR3B gene in this patient, and they were novel mutations, which were respectively inherited from her father and mother validated by Sanger sequencing. Bioinformatic analysis predicted these two mutations were pathogenic.Conclusion:The clinical and imaging features of POLR3B-associated leukodystrophy with hypogonadism were considerably evident, diagnosis and treatment of which should be conducted as early as possible.

Characteristics of apolipoprotein E genotype and cognitive impairment in patients with cerebral microbleeds and positive β amyloid / 中华老年医学杂志

Objective:To analyze the characteristics of the apolipoprotein E(Apo E)genotype and cognitive impairment in patients with cerebral microbleeds(CMBs)and positive β-amyloid(Aβ)by using [18F]-AV45 positron emission tomography(PET).Methods:From September 2015 to May 2018, 152 patients with cognitive impairment and CMBs on the susceptibility-weighted imaging(SWI)sequence of head MRI at the neurology department of our hospital, assessed by mini-mental status examination(MMSE)score ≤26 and Montreal cognitive assessment(MoCA)≤25, were consecutively recruited in this retrospective study.After assessment with the inclusion and exclusion criteria, 69 patients aged 68.8±9.3 years were considered eligible for further analysis.Patients were divided into the Aβ-positive group(Aβ + Group, n=37)and the Aβ-negative group(Aβ -Group, n=32)after cognitive assessment, ApoE genotyping and [18F]-AV45 PET examination.Twenty-one healthy elderly controls(HC Group)who took health examination during the same period were enrolled.The results of cognitive assessment and Apo E genotyping were compared between the three groups. Results:The positive rate of the ApoE ε4 allele was 35.6%(32/90), 56.8%(21/37), 18.8%(6/32), and 23.9%(5/21)in the Aβ + , Aβ -and HC groups, respectively, with statistical significant differences between the groups( χ2=12.467, P<0.01). There were significant differences in the positive rate of the ApoE ε4 allele between the Aβ + and HC groups and between the Aβ + and Aβ -groups( χ2=5.880 and 10.407, P<0.05 and P<0.01). The percentage of patients with deep cerebral microbleeds was higher(56.3% or 18/32 vs.8.1% or 3/37, χ2=18.784, P<0.01)and of patients with lobar hemorrhage was lower(12.5% or 4/32 vs.45.9% or 17/37, χ2=9.066, P<0.01)in the Aβ -group than in the Aβ + group, while there was no significant difference in the percentage of patients with mixed cerebral microbleeds between the Aβ -and Aβ + groups( χ2=1.556, P>0.05). There were significant differences in cognitive function between the Aβ + and HC groups, in memory, executive function, visuospatial ability and language between the Aβ + and Aβ -groups, and in executive function, visuospatial ability and attention between the Aβ -and HC groups. Conclusions:Cognitive impairment is more extensive and severe in CMBs patients with Aβ deposition and is associated with positive ApoE ε4.

Subjective memory decline:risk factors and advances in neuroimaging research / 中华老年医学杂志

Subjective memory decline is one of the most common symptoms reported in the elderly,which is considered as a high-risk factor for dementia.This article presented an overview of an update of definition and epidemiology of subjective memory decline,reviewed its risk factors,and summarized neuroimaging changes in brain structure and function.Finally,some suggestions for future research were also proposed.

A study on language features in Alzheimer's disease versus behavioral variant frontotemporal dementia / 中华老年医学杂志

Objective To investigate and compare the language features among patients with behavioral variant frontotemporal dementia(bv-FTD),Alzheimer's disease(AD) and healthy controls,and to determine the clinical value of language tests in the diagnosis and differential diagnosis of the two kinds of dementia diseases.Methods A total of 17 bv-FTD patients,18 AD patients and 18 healthy controls were enrolled in Beijing hospital from Nov.2012 to Dec.2013.The language performances in four aspects of listening,speaking,reading and writing by seven items of listening comprehension,repetition,naming,speaking,read aloud,reading comprehension and writing were compared by using the one-way analysis of variance(ANOVA)and least significant difference(LSD)tests.Results There were significant differences among the three groups in speaking general scores (AD 128± 46,bv-FTD 113 ± 19,controls 158 ± 13) (F =23.34,P =0.049) and in writing (AD 8 ± 5,bv-FTD 8 ± 4,controls 11 ± 1) (F =27.07,P =0.000).A t rend of statistical difference was observed in general scores of listening comprehension(F =20.96,P =0.060).No difference was found in general scores of repetition,in naming,in reading aloud and in reading comprehension(all P ＞ 0.05).As compared with controls,bv-FTD patients were comprehensively impaired in sub-items of listening comprehension,in naming and in speaking(all P ＜0.05).As compared with controls,AD patients were significantly impaired in a few sub-items of listening comprehension,in naming and in speaking(P ＜0.05).There were significant differences in naming objects,grammar and word finding between AD patients and bv-FTD patients(51± 19 vs.47±13,6±1 vs.6±1,6±1 vs.6±1,P=0.037,0.010 and 0.021,respectively).Conclusions The detailed language examinations are helpful for screening AD and bv-FTD.However,the values are limited in the differential diagnosis between the two types of dementia diseases.It is necessary to combine the detailed language examinations with other tests.

Diagnostic value of 18F-AV45 positron emission tomography for cerebral microbleeds of different regions / 中华老年医学杂志

Objective To analyze the relationship of cerebral microbleeds (CMBs)of different regions,especially mixed-CMBs,with cerebral amyloid angiopathy (CAA)detected using 18F-AV45 positron emission tomography(PET).Methods A total of 52 consecutive patients (68.17 ± 9.89 years old)with memory decline and CMBs found in susceptibility-weighted images(SWI)according to the inclusive and exclusive criteria were recruited.Patients were divided into three groups based on different regions of CMBs,the strictly lobar CMBs (SL-CMBs) group,the deep-CMBs (D-CMBs) group and the mixed-CMBs (M-CMBs)group.Patients in the three groups underwent 18F-AV45 PET detection and then were analyzed based on the results of 18F-AV45 PET.Results The positive rates of cerebral amyloid angiopathy in the SL-CMBs,M-CMBs and D-CMBs groups were 68.4 ％ (13/19),82.4 ％ (14/17) and 25.0 ％ (4/16),respectively,with statistical significance (P =0.002).There were significant differences in positive rates of cerebral amyloid angiopathy between the D-CMBs group and the M-CMBs group and between the D-CMBs group and the SL-CMBs group(P =0.001 and 0.010,respectively),while there was no difference between the M-CMBs and SL-CMBs groups in positive rates of cerebral amyloid angiopathy(P =0.335).Using the D-CMBs group as the reference group,multivariate logistic regression analysis showed that the odds ratios of positive CCA detected by PET in SL-CMBs and M-CMBs were 30.585(95％CI:2.492-375.360)and 8.107(95％CI:1.072-61.295),respectively.Conclusions Compared with D-CMBs,M-CMBs and SL-CMBs are more likely to be related to cerebral amyloid angiopathy.The presence of M-CMBs also indicates that patients have a high probability of CAA.

Analysis of gene and imaging on a late onset Alzheimer's pedigree concomitant with presenilin 1 mutation / 中华行为医学与脑科学杂志

Objective To analyze the clinical manifestation,imaging data and genetics mutation variants of late onset familial Alzheimer's disease concomitant with a novel mutation of presenilin 1.Methods The clinical manifestations and auxiliary examination recordings of the pedigree were analyzed.DNA was extracted from peripheral blood samples of the proband and her sons.Mutational analysis was performed by the next-generation sequencing technology and the mutation event was confirmed by Sanger sequencing technology.Results Two patients of the family presenting as Alzheimer's dementia were late onset.MRI of the proband showed extensive cerebral microbleeds.The gene detection showed p.S289P mutation in the exon 8 of presenilin 1 of the proband.Conclusion Mutation of p.S289P in the presenilin 1 gene may contribute to late onset Alzheimer's disease accompanied by amyloid angiopathy.

Clinical and genetic analysis of a patient with Perrault syndrome and additional neurological features / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation.@*METHODS@#Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing.@*RESULTS@#The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines.@*CONCLUSION@#Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.

Diagnostic significance of the difference values between Mini-Mental State Examination and Montreal Cognitive Assessment in elderly patients with dementia / 中华老年医学杂志

Objective To investigate the diagnostic significance of the difference values between Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)in elderly patients with dementia.Methods 331 elderly patients with dementia were collected from outpatients in our hospital.There were 148 people with Alzheimer's disease (AD),87 cases with vascular dementia (VaD),44 cases with mixed dementia (MD),41 cases with frontotemporal dementia (FTD) and 11 cases with dementia with Lewy bodies (DLB).MMSE and MoCA were applied to test the cognitive impairment separately.Results The difference values between MMSE and MoCA was (3.3±1.7) points,(6.6±2.1) points,(6.6±2.1) points,(5.4±2.3) points,(6.1 ± 1.9) points in AD,VaD,MD,FTD and DLB group respectively,and there were statistical differences among the five groups (F=46.420,P=0.000).Statistical differences were found in the difference values between MMSE and MoCA between dementia patients with AD and non-AD (t=-13.429,P=0.000).According to receiver operating characteristic curve (ROC curve),the optimal cut off point of the difference values between MMSE and MoCA for differential diagnosis between AD and non-AD dementia was 5 points,with 79.8％ sensitivity and 78.4％ specificity,and area under the curve was 0.848 (95％CI:0.807-0.890).Conclusions The difference values between MMSE and MoCA may be one of parameters for differential diagnosis between AD and non-AD dementia.

Clinical study of deep brain magnetic stimulation technique in the treatment of Alzheimer's disease / 中华老年医学杂志

Objective To explore the effectiveness and safety of deep brain magnetic stimulation technique (dTMS) for treatment of Alzheimer's disease (AD).Methods Totally 116 patients with AD were randomly divided into 4 groups:(1) dTMS:given dTMS really stimulation therapy,(2)medication group:treatment with donepezil 5 mg/d,(3) combination treatment group:given dTMS and donepezil therapy,(4) blank control group:given pseudorandom stimulation treatment.33 healthy control cases were given dTMS's stimulation treatment.The treatment course was 6 months.Application of mini mental state examination scale (MMSE),the Montreal cognitive assessment scale (MoCA),Hamilton Depression Scale (HAMD),ischemic scale (HIS),Boston naming test,activity of daily living(ADL) and neuropsychological questionnaire (NPI) were used to evaluate the cognitive function.All the participants received blood tests and ECG in order to evaluate the safety of dTMS.Results After 6 months treatment,compair with the blank control group,all scale scoresof dTMS group,medication group and combined treatment group were improved significantly in MMSE (t=2.49,2.46,2.20),MoCA(t=2.59,2.39,2.87),ADL(t=2.35,2.17,2.83),NPI(t=3.05,2.40,2.65) and sub-cognitive scale score (all P＜0.05).All scale scores of combination treatment group were better than dTMS group and medication group (P＜0.05).There's no significant difference between drug treatment groups and dTMS group (P＞0.05).After 6 months treatment,compared with healthy control group,the scale scores were aggravated in 4 groups of AD (P＜0.05)Conclusions dTMS can be effective and safe in the treatment of AD patients with cognitive and noncognitive symptoms.

Value of Alzheimer-associated neuronal thread protein level in urine for diagnosing Alzheimer's disease / 中华老年医学杂志

Objective To investigate the value of Alzheimer-associated neuronal thread protein (AD7c-NTP) level in urine for diagnosing Alzheimer's disease (AD). Methods The urine samples of 450 subjects were collected from out-department of our hospital.There were 257 people with AD diseases (131 mild cases,126 moderate and severe cases) and 193 healthy control.ELISA was applied to test the level of AD7c-NTP in urine samples. Results The levels of AD7c-NTP were (1.94±0.74)μg/L,(3.92 ± 0.86 ) μg/L and (0.65 ± 0.80) μg/L in mild AD,moderate and severe AD,healthy control groups,respectively.There were differences among three groups(F=-13.520,P＜0.001),and between mild and moderate and severe AD(t =1.727,P＜ 0.001).The level of AD7c-NTP was negatively related with MMSE score in mild AD (r =- 0.23,P =0.006),while no correlation was found between AD7c-NTP and MMSE in moderate and severe AD(r=0.59,P =0.113).Using receiver operating characteristic curve(ROC curve),the optimal cutoff point of AD7cNTP in urine for diagnosis of AD was 1.50 μg/L,with 90.6％ sensitivity and 91.8％ specificity,area under the curve was 0.94(95％ CI:0.91-0.97). Conclusions The level of AD7c-NTP in urine may be one of parameters for diagnosing AD.

A survey of the consultative status of patients with Alzheimer disease and the efficacy and safety of donepezil treatment / 中华老年医学杂志

Objective To investigate the consultative status of patients with Alzheimer Disease (AD), and to evaluate the efficacy and safety of donepezil (Aricept) in the treatment of AD.Methods This survey was initiated by Chinese society of Geriatrics, and was sponsored by Eisai (China) Inc. It was conducted in 60 hospitals of 40 cities in China. The diagnosis of dementia was made according to ICD-10 and DSM-Ⅳ criteria. The cognition, behavior and ability of daily living of the patients were compared before and after 3-month treatment with donepezil. Results A total of 808 dementia patients were recruited. The main reasons for patients' seeing doctors included memory problem (n= 703, 87%), behavioral and psychological symptoms (n= 250, 31%), impairment of ability of daily living (n= 388, 48% ). The disease course was from 9 months to 16 months, and mean disease course was (13.0 ±0. 2) months. Patients mainly sought treatment from neurologist (74 % ),psychiatrist (6 % ) and geriatrics ( 19 %). They received dementia diagnosis at ( 14.4 ± 0.3) months after their dementia symptoms appeared. Treatment with donepezil for three months improved their cognition, ability of daily living and mental condtion (all P＜0.05). The main adverse effects were nausea, vomiting etc. Conclusions In China, the percentage of people with dementia seeking treatment is low. Most people with dementia see doctors when they reach moderate and severe stages,which affects the efficacy of treatment and daily activity of the patients. Treatment with donepezil for 3 months is effective in improving cognition, behavior and activity of daily living.

The preliminary study on assessment of cerebral blood flow by arterial spin-labeling magnetic resonance imaging in patients with Alzheimer's disease / 中华老年医学杂志

Objective To explore the clinical utility of arterial spin-labeling (ASL) magnetic resonance(MR)imaging for the detection of cerebral blood flow (CBF) abnormalities in patients with Alzheimer disease(AD). Methods Twenty-two subjects with probable AD and twenty normal control subjects underwent ASL and structural MR imaging. Among them, 16 AD patients and 11 control subjects were also examined with single photon emission computed tomography(SPECT). The CBF images were obtained by processing ASL perfusion data. The CBF values of bilateral frontal lobe, temporal lobe, temporoparietal junction, parietal lobe, occipital cortices and hippocampal areas were measured by CBF images. And the CBF values of cerebral structures between AD and control subjects were compared. Results ASL perfusion imaging in AD revealed marked hypoperfusion mainly in temporal lobe (72.7%), temporoparietal junction (54.5%), parietal lobe(45.5%). The brain regions involved were similar to those seen with SPECT. The CBF values of bilateral frontal lobe, temporal lobe, temporoparietal junction, parietal lobe and hippocampal areas were significantly decreased compared with control subjects (all P<0.05). The CBF values of right frontal lobe, left temporoparietal junction, left parietal lobe in patients with AD were positively correlated with the mini-mental state examination score (r= 0.49, 0.54, 0.64, all P<0.05). Conclusions ASL MR imaging can show regional hypoperfusion in AD patients, which is similar to that seen with SPECT. The results suggest ASL MR imaging is an useful tool for assessment of cerebral blood flow in patients with AD.

Multicenter controlled randomized clinical trial of akatinol memantine for treatment of Aizheimer's disease / 中华神经科杂志

Objective To evaluate the clinical efficacy and safety of akatinol memantine in the treatment of Alzheimer's disease (AD).Methods Two hundred and forty-one patients with AD were randomly assigned to receive 10 mg of donepezil daily or 20 mg of memantine daily for 24 weeks.The primary efficacy variables were the Clinician' s Interview-Based Impression of Change Plus (CIBIC-Plus),the Alzheimer Disease Assessment Scale-cognition (ADAS-cog) and the Activities of Daily Living (ADL).The secondary efficacy variables were the Neuropsychiatric Inventory (NPI) and the Mini-Mental Status Examination (MMSE).Results Two hundred and seven patients completed the study and were evaluated at week 24.Both memantine and donepezil had significant efficacies at the end point, according to the ADAS-cog, the ADL, the NPI and the MMSE.Patients receiving memantine had a similar outcome as those receiving donepezil, according to the results of all the variables changes (CIBIC-Plus: memantine 3.4±0.8vs donepezil 3.5±0.8; ADAS-cog: memantine-4.7±5.8 vs donepezil-4.6±6.5; ADL: memantine -2.4±6.7 vs donepezil-2.2±5.3 ; NP1: memantine-5.8±9.0 vs donepezil-3.1±8.5 ; MMSE:memantine 1.7±3.1 vs donepezil 1.8±2.8, all P >0.05).The adverse events were as following: donepezil group 41.88% and memanintine group 30.58%.Conclusion The memantine as a new drug for AD, has the similar efficacy as donepezil, and it is safe.

Efficiency and safety assessment of donepezil for treating mild and moderate Alzheimer disease / 中国组织工程研究

BACKGROUND: As the second anti-Alzheimer disease drug approved by Food and Drug Administration(FDA), donepezil (Aricept) has been applied in European and American market. According to the regulation of Health Ministry of China, it needs conducting clinical trial of multiple center nationwide in order to come into Chinese market.OBJECTIVE: To evaluate the efficiency and safety of donepezil on treating mild and moderate Alzheimer disease (AD).DESIGN: Randomized, single blind and placebo control prospective study based on patients.SETTING: Neurological Department of Peking Hospital and Neurological Department of the 301 Hospital of Chinese PLA, and ect.PARTICIPANTS: Totally 188 patients with mild and moderate AD[with mini-mental state examination(MMSE) score of 10 to 24 points] from 15 big hospitals of Beijng, Shanghai and Guangzhou were conducted 12 weeks'clinical trial, among which 89 cases were of single blind and placebo control study while 99 cases were of self-controlled study. All the cases met the AD diagnostic standard of clinical neurology, linguistic dysfunction and stroke(NINCDS-ADRDA) and the 4th edition of Statistic Manual (DSM-IVR).INTERVENTIONS: Donepezil (5 rmg/tablet, ip, 5 rmg/time) or placebo with same color, shape, flavor and size with donepezil ( ip, 1 tablet/time)was taken orally for 12 consecutive weeks.MAIN OUTCOME MEASURES: MMSE, clinical dementia rating scale(CDR), activities of daily life scale(ADL), biochemical parameters, electrocardiograph(ECG) and chest x-ray were conducted once every 4 weeks before and after treatment.RESULTS: The random, single blind and placebo control study showed that the score of MMSE, CDR and ADL was greatly improved in donepezil group after 12 weeks' treatment when comparing with placebo group(P ＜ 0. 01,0.05, 0.01 ). Self-controlled study showed that the score of MMSE, CRD and ADL in donepezil group after 12 weeks' treatment increased 3.5, 0.6 and 7.1 points respectively compared with those before treatment(P ＜ 0.01,0.05, 0.01 ) . The score of MMSE was already improved in the 4th week of treatment. Among the 145 patients who took donepezil, 7 cases(4.8% )experienced side effect of mild cholinergic excitability. In the placebo group,2 of the 43 cases appeared dizziness and nausea. There was no difference between two groups( P ＞ 0.05).CONCLUSION: Donepezil can effectively treat mild and moderate AD patients and improve their cognitive functions, dementia level and daily living abilities with good tolerance and high safety.

Evaluation of the role of plasma level of p-tau(~ (181)p) protein for clinical diagnosis of Alzheimer′s disease / 中华老年医学杂志

Objective To evaluate the roles of plasma p-tau(~ 181P)protein for clinical diagnosis of Alzheimer′s Disease (AD). Methods Subjects including 23 mild AD(19≤MMSE≤26) and 35 moderate and severe AD(MMSE0.05). Level of p-tau(~ 181P) protein was significantly higher in the moderate and severe AD group(18.3?20.3)ng/L than that in HC( P

The safety and efficacy of aricept in patients with Alzheimer disease / 中华神经科杂志

Objective To assess the efficacy and safety of aricept in treatment of mild to moderate Alzheimer disease(AD).Methods 188 patients with AD were followed up in a multicentre,with randomized study for 12 weeks. 89 patients had a single -blind,placebo-controlled trial and 99 a self-matched trial.Results The results of randomized single-blind,placebo-controlled trial showed that the improvements in MMSE、CDR and ADL were statistically significantly greater with aricept 5 mg/d than with placebo(P value respectively 0.05).Conclusion Aricept is effective in treating patients with mild to moderate AD. It could produce improvements in cognition and ability of daily life. Aricept was well tolerated and safe.