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Alzheimer′s disease is a progressive neurodegenerative disease that requires medication to improve patient symptoms, but there is an individual difference in the efficacy. In this paper, the correlation between single nucleotide polymorphism and the drug efficacy of Alzheimer′s disease (AD) in the past 20 years was searched through the databases of China National Knowledge Infrastructure, VIP Database, Wanfang Database, Pubmed, Springer Link and Cochrane Library with key words of Alzheimer′s disease, drug efficacy, single nucleotide polymorphism. The correlation between AD drug efficacy difference and gene single nucleotide polymorphism was reviewed, including ABCA1, ApoE, ChAT, CHRNA7, IL-6, A2M, CYP2D6, BChE, 5HT2a, PON-1 and ESR1 genes, so as to provide a reference basis for clinicians to select drugs in the treatment of AD.
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Objective To explore the features of connected speech produced by Chinese mild Alzheimer's disease (AD) patients.Methods Thirty Chinese mild AD patients (eight males and 22 females,and the age was (72.73 ± 7.78) years) and 30 age and education matched normal controls from three communities were recruited in Xuanwu Hospital from January 2018 to May 2018.All subjects completed tasks of picture naming,semantic fluency (animal),and Cookie Theft picture description.Picture description was analyzed for speech production (total word output,speech rate,sound errors),lexical content (number of nouns and verbs,proportion of pronouns and verbs,semantic errors),information content (information unit,idea density,efficiency),syntactic structure and complexity (mean length of utterance,words in sentences,syntactic errors).Differences between groups were calculated.Association between picture naming,semantic fluency,and measures in picture descriptions was analyzed.Results Compared with the controls,mild AD patients achieved lower scores on the picture naming task (74.45±8.04 vs 79.60± 1.73,t=-2.800,P=0.010) as well as on the semantic fluency task (10.35±3.08 vs 18.50±4.66,t=-6.520,P＜0.01) and produced lower speech rate (131.80±36.40 vs 149.64±26.69,t=-2.095,P=0.041),less number of nouns (7.52±2.55 vs 9.67±3.58,t=-2.509,P=-0.015) and verbs (4.40±2.24 vs 5.73±1.92,t=-2.375,P=0.021),increased proportion of pronouns (0.286 (0.319) vs 0.039 (0.122),Z=3.602,P＜0.01) and semantic errors (0.629 (1.396) vs 0 (0.779),Z=2.386,P=0.017),less information units (11.00±3.63 vs 13.70±3.53,t=-2.787,P=0.007),decreased idea density (0.11±0.04 vs 0.16±0.05,t=-3.946,P＜0.01),decreased efficiency (14.23±7.56 vs 22.95±7.14,t=-4.738,P＜0.01),shorter mean length of utterance (6.64± 1.27 vs 8.25± 1.70,t=-3.928,P＜0.01),and less words in sentence (0.84±0.10 vs 0.95±0.06,t=-4.625,P＜0.01).Group differences in total word output,sound errors,proportion of verbs,and syntactic errors did not reach statistical significance.Scores on picture naming task were negatively associated with the proportion of pronouns (r=-0.737,P=0.003),and positively associated with the idea density (r=0.540,P=0.046) and efficiency (r=0.592,P=0.026) in the AD group.Scores on semantic fluency task were negatively associated with the proportion of pronouns (r=-0.554,P=0.011).Conclusions Connected speech in mild AD patients was characterized by decreased naming accuracy,decreased sematic fluency,decreased content words,information units,conciseness,efficiency,and syntactic complexity,but motoric aspects of speech and sentence structure remained relatively preserved.Decreased content words and increased pronouns in mild AD may relate to semantic impairment.
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Objective@#To explore the influencing factors affecting the cognitive impairment of the elderly population in China.@*Methods@#A stratified multi-stage cluster sampling was used in 6 provinces (autonomous administrative regions and municipalities) to select the sample. A total 24 000 urban and rural residents aged 60 years and above received a set of standardized questionnaire interview, physical examinations, laboratory test of lipid and glucose levels of blood and apolipoprotein E (APOE) genotype. The primary screening of cognitive function was assessed by using the Chinese Version of Ascertain Dementia 8, and then suspicious cognitive impairment cases with more than two abnormal results would receive the further cognitive function assessment by using the Mini-Mental State Examination (MMSE). 1 300 cases with cognitive impairment and 2 600 controls without cognitive impairment were recruited and matched according to their age, gender and resident area in a 1∶2 case-control study. The conditional logistic regression model was used to analyze the association between relevant factors and cognitive impairment.@*Results@#Factors negatively associated with cognitive impairment and their OR (95%CI) values were primary or middle school as 0.63 (0.51-0.77), high school and above as 0.59 (0.39-0.88), daily neighborhood communication as 0.61 (0.50-0.75), weekly participating in social activities 0.59 (0.44-0.79), daily tea drinking as 0.71 (0.58-0.88) and doing regular exercise as 0.71 (0.57-0.88), reading newspaper (occasional: 0.50 (0.37-0.67); frequent: 0.40 (0.28-0.57)), playing majiang or cards (occasional: 0.51 (0.34-0.74); frequent: 0.50 (0.36-0.68)) respectively. Factors positively associated with cognitive impairment and their OR (95%CI) values were APOE-ε4 heterozygote as 1.31 (1.08-1.58), homozygote as 2.74 (1.52-5.00), diabetes onset before 50 years of age and after as 9.03 (3.07-33.60) and 4.40 (3.18-6.17), stroke as 1.90 (1.35-2.69), asthma as 1.95 (1.11-3.42) respectively.@*Conclusion@#APOE-ε4 alleles, lower educational level, stroke, asthma, diabetes are risk factors of cognitive impairment in the elderly. Keeping a healthy lifestyle and preventing chronic diseases in the whole life course could significantly reduce the incidence of cognitive impairment in the elderly.
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Objective: To develop an LC-MS/MS method for the determination of donepezil and rivastigmine in human serum. Methods: After protein precipitation with 600μl acetonitrile, the serum samples were analyzed by LC-MS/MS. Using loratadine as the internal standard, a Waters Xselect CSH C18(150 mm×3 mm, 2. 5 μm) column was used with the mobile phase consisting of water (containing 10 mmol·L-1ammonium acetate)-acetonitrile(20 ∶ 80)at a flow rate of 0. 4 ml·min-1with the column temperature at 40 ℃. The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding [M+H] +as the molecular ion peak of donepezil and rivastigmine monitored with m/z 380. 1→m/z 91. 1 and m/z 251→m/z 206. 5, respectively. The internal standard was monitored with m/z 383. 1→m/z 337. 1. Results: The linear range of donepezil and rivastigmine was 0. 5-400 ng·ml-1(r>0. 99) and the lowest quantification limit was 0. 5 ng·ml-1. For donepezil, the intra-day and inter-day RSD was 2. 06% to 12. 51% , the relative error was -6. 60% to 4. 20% , and the relative recovery was ranged from 80. 76% to 96. 17% (RSD<15% ). For rivastigmine, the intra-day and inter-day RSD was 1. 69% to 9. 31% , the relative error was -5. 58% to 5. 20% , and the mean relative recovery was ranged from 96. 69% to 100. 15% (RSD<15% ). For the two compounds, the serum samples were stable at -40℃ for 75 d and kept stable after three repeated freeze-thaw cycles. The prepared samples were stable in the automatic sample injector (4℃) for 5 h (RSD<15% ). Conclusion: The developed assay method can be applied in the therapeutic monitoring and pharmacokinetic study of donepezil and rivastigmine in human serum.
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Objective To explore the value of urine formaldehyde test in the diagnosis of Alzheimer's disease (AD),and the influential factors of urine formaldehyde level in AD patients.Methods A total of 52 AD patients and 53 cognitively normal controls were recruited in a cohort study.All subjects were no less than 65 years old,and those with acute infection,or dysfunction in heart,liver or kidneys were excluded.The impact of age,gender,onset age,MMSE score,NPI score,MTA score,and ApoE ε4 gene on urine formaldehyde of AD patients were analyzed by multiple regression analysis.Results Urine formaldehyde level of AD group was statistically higher than that of cognitively normal control group ((13.27±4.16)μmol/L vs (10.76±4.47)μmol/L,t=2.99,P=0.15).Urine formaldehyde of AD patients was statistically negatively correlated with MMSE score (β=-0.35,P=0.03) and MTA score (β=-0.38,P=0.02).The impact of onset age,neuropsychiatric disorders and ApoE ε4 gene on urine formaldehyde of AD patients was not statistically significant(all P>0.05).Conclusion Urine formaldehyde level is worthwhile to be explored as a marker in AD diagnosis and severity assessment.
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Objective To explore the clinical,neuroimage,and neuropsychological profiles of semantic dementia (SD).Methods Detailed medical history were collected on 18 SD patients.Brain MRI scans were administered.Neuropsychological evaluation taping semantic memory (things naming),overall cognitive function ( Mini-mental State Examination,MMSE),visuoconstructive skill ( Clock Drawing Test,CDT), daily functional ability (Activities of Daily Living, ADL), neuropsychiatric symptoms (Neuropsychiatric Inventory,NPI),and disease severity (Frontotemporal Lobar Degeneration Modified Clinical Dementia Rating Scale,FTLD-CDR) were performed on all patients.Results The mean age at onset was (60.6 ± 8.5 ) years,with 5 cases over 65. All patients developed progressive word-finding difficulty and anomic speech.Ten patients complained significant memory impairment and 14 experienced behavioral disturbance.Five patients were previously diagnosed as Alzheimer' s disease (AD) and 1 as schizophrenia.All patients developed marked semantic memory impairment both for living things and nonliving things.The mean score on MMSE was 10.94 ± 8.86,with 16 cases performed incorrectly on naming.Mean score on CDT copy was 4.61 ±0.85,with 14 cases scored normally.Mean score on ADL was 29.72 ± 8.75.Cases with a 5-year course showed a significant overall decline.Fourteen cases presented behavior symptoms and scored 8.00 ± 7.22 on NPI.All patients scored worst on language domain among all the domains evaluated in FTLD-CDR.Atrophy,typically involving the left anterior temporal was shown on MRI scans.However,predominantly right temporal atrophy was observed in one patient.Atrophy confined to the temporal lobe in patients with early stage and extended to the contralateral temporal,frontal lobe,and parietal lobe as disease progression. Conclusions Current study suggested that SD tend to develop in presenile age.However,about 1/3 cases develop the disease after 65 years. Deficit in language is the earliest and most prominent symptom. Behavior change is prevalent as well. Patients are commonly misdiagnosed as AD or lack a definite diagnosis.Visuoconstructive skill and other abilities are relatively preserved in the early stage.With progression into the 5th years,overall decline comes inevitably.Brain scans can reflect the disease characteristics and progression. Of note,there exists individual with right dominant atrophy.
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Objective To determine the risk factors and clinical features of mild vascular cognitive impairment due to subcortical small vessel disease (mVCI-SSVD).Methods Detailed demographic data,vascular risk factors, past and present history were collected and carefully neurological examination, National Institutes of Health Stroke Scale (NIHSS), as well as Hachinski ischemic score (HIS) were performed on 56 mVCI-SSVD patients.Further, the demographic data and vascular risk factors of mVCI-SSVD patients were compared with those of 80 normal control subjects.Results Proportions of smoking (39.3% (22/56)), hypertension (67.9% (38/56)), and diabetes (25.0% (14/56)) were higher in the patient group than in the normal control group (21.3% (17/80) , 47.5% (39/80), 11.3% (9/80)).Odds ratio (2.32(95% CI 1.05-5.13),2.15 (95% CI 1.02-4.54),2.26(95% CI 0.86-5.92)) between the two groups was statistically significant (P value: 0.039, 0.045, 0.047).There was no difference in terms of hyperlipidemia and cardiac disease between groups.Fifty percent (28/56) mVCI-SSVD patients had a clear stroke history.Twenty-six point eight percent (15/56) patients developed the cognitive impairment with an acute onset.Neurological focal signs presented in 20 patients (35.7%).Twenty four (42.9%) patients with HIS ≤ 4 points.Thirty eight cases (67.9%) scored 0 on NIHSS.Conclusions Current study suggested that smoking, hypertension, and diabetes may be risk factors for mVCI-SSVD.While hyperlipidemia and cardiac disease do not increase the risk of mVCI-SSVD.Unlike mVCI caused by large vessel disease, about half mVCI-SSVD patients lack of stroke history.Most patients show a relatively insidious onset and free of significant neurological focal signs.
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Objective To study the effect of lovastatin on the expression and activity of β-site APP cleaving enzyme (BACE1). Methods The SH-SY5Y cells were treated by lovastatin. Cell viability was assessed by MTT assay, and the levels of cholesterol were assayed spectrophotometrically, and the activity of BACE1 was detected by fluorometric assay, and the expression level of BACE1 was detected by Western Blot. Results Compared with the control group, the cholesterol levels were decreased by 33.0% (3.33 vs. 4.97; F=5.13, P =0.020) and the activity of BACE1 was reduced by 13.8% (343.14 vs. 398.22; F=3.773, P =0.035) after 24h treatment of 5μmol/L lovastatin; the cholesterol levels were decreased by 49.2% (2.65 vs. 5.22; F=12.239, P =0.001) and the activity of BACE1 was reduced by 38.0% (274.75 vs. 443.14; F=13.610, P <0.01). Treatment with 5μmol/L lovastatin,for 48 h did affect the expression level of BACE1. Conclusions Lovastatin do not affect the expression level of BACE1, but may inhibit its activity and decrease the cholesterol level, thus providing a new approach to prevent or treat Alzheimer's disease (AD).
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Objective: To investigate the clinical therapeutic effects on ischemic stroke by syndrome(differentiation) in traditional Chinese medicine(TCM) combined with differential diagnosis in western medicine.Methods: One hundred and thirtyeight cases suffered from ischemic stroke were randomly divided into treatment group and control group,and according to TCM(theory) the(treatment) group was subdivided into Qideficiency(气虚),phlegm(dampness)(痰湿),phlegmfire(痰火) and Yindeficiency(阴虚)(subgroups).(Different) TCM decoction was administrated respectively to the four subgroups.The clinical(symptoms) and signs,tongue picture of TCM diagnosis as well as the changes of national institutes of health stoke score(NIHSS) were observed and compared with those of the control group before and after treatment.Results: NIHSS scores were improved in all the groups(P
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Objective To study effects of Ginsenoside Rg1,Rb1 on activity and genetic expression of alpha secretase in the progress of metabolism of APP.Methods Chinese hamster ovary (CHO) cell line transacted by mutant PS1 (ML46L) genes and wild type PS1 genes was used.The activity of alpha secretase was tested by fluorometric reaction.The expression of ADAM9 and ADAM10 was analysis through western blotting and RT-PCR.Results The activity of alpha secretase was increased significantly in Ginsenoside Rg1,Rb1 group than that without Ginsenoside group (P
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BACKGROUND: The previous experiments have conformed the traditional Chinese medicine (TCM) Jiannaaan, with the effects of tonifying kidney, promoting blood circulation and resolving phlegm, can inhibit the increased content of glucocorticoid (GC) in 2-24 hours after cerebral ischemic reperfusion (CIR), and reduce toxic effects of promoting nervous cell apoptosis induced by high GC. However, it is unclear whether this effect exists in GC receptor (GR).OBJECTIVE: To observe the intervention of TCM Jiannaoan on GR,further study protective mechanism of Jiannaoan power to hippocampal neurons after CIR, and perform positive control with compound almitrine.DESIGN: A randomized and controlled trial taken animals as subjects.SETTING: Center Laboratory of Beijing University of Chinese Medicine.MATERIALS: The experiment was conducted at the Center Laboratory of Beijing University of Traditional Chinese Medicine between July 2002 and March 2003. Eighty male SD rats were randomized into 5 groups with 16 in each: Sham group, model group, treatment group, positive control group and antagonist group. And each group was divided into 4 subgroups: 2, 6,12 and 24 hours after CIR, with 4 rats at every time point.METHODS:①Administration: Except model group, rats in other 4 groups were administrated by intragastric infusion since 7 days before model establishment, once per day, with dose of 7 μL/g per day distilled water in sham group, 7.39 mg/kg per day compound almitrine in positive control group, 6.7 g/kg per day Jiannaoan crude drug (consisted of desertliving cistanche herb, tatarinowii sweetflag rhizome and rhubarb, etc) in treatment group and 10 g/kg per day GR antagonist mifepristone in antagonist group.② After 7-day administration, the CIR models were prepared on the experimental rats with middle cerebral artery occlusion (MCAO) filament method, while the rats in sham group were sutured after common carotid artery detachment at anesthesia, without filament.MAIN OUTCOME MEASURES: All the rats were executed to take out brains at different time points of reperfusion, and the change of GR protein expression was observed with immunohistochemical method then the amount of positive cells were calculated in 3×200 sight of CA2 region.RESULTS: Totally 80 rats were entered into the result analysis. Compared with uninjured side, the protein expression of GR in model group,treatment group, positive control group and antagonist group were significantly lower than that of sham group (P ＜ 0.05), in which GR expression of injured side was equal to that of uninjured side without significant difference. No obvious change was found in the protein expression of GR among treatment group, positive group and antagonist group at different time points of reperfusion, and no significant difference was found between above groups and model group (P ＞ 0.05).CONCLUSION: Jiannaoan power is selective for adjusting GR and content of GC: Jiannaoan can not adjust expression of GR, identical as compound almitrine; But Jiannaoan can protect the neurons through decreasing the content of GC in plasm and brain tissues after CIR.
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Objective:To study protective e ects of ginsenoside Rg1,Rb1 on cultured CHO cell injure induced by beta-amyloid protein 25-35(A?25-35).Methods:MTT assay was used to measure the cell viability after incubated with 40?mol/L A?25-35 for 24h and ginsenoside Rg1,Rb1 added into substratum.The e ect of anti-apoptosis of ginsenoside Rg1 and Rb1 were assayed through ow cytometric analysis.Results:Compare with the control group,the cellular activity was decreased(P
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AIM: To investigate the relationship between glucocorticoid (Gc) and injury of hippocampus neurons and the effect of Gc on dementia episode after cerebral ischemia-reperfusion. METHODS: The rat model of middle cerebral artery occlusion (MACO) was established. Cortisol contents in hippocampus and plasma of the model rats were examined by means of the radioimmunoassay at 2 h, 6 h, 12 h, 24 h after reperfusion. RESULTS: The levels of cortisol content in model group were significantly higher than those in sham group and normal group both in hippocampus and plasma. The highest cortisol content was observed at 6 hours after reperfusion. HE staining showed that the impairment of hippocampus neurons was aggravated progressively with reperfusion interval elongating. CONCLUSION: The increased cortisol in hippocampus and plasma, after 2 h cerebral ischemia and 24 h reperfusion, could aggravate the injury of hippocampus neurons and lead to dementia post stroke.