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世界核心医学期刊文摘（神经病学分册） 2006年第9期2卷 4-5页

作者： Winbl.d B. kilander l. Eriksson S. 周永(译) Karol.nska Institutet Alzheimer's Disease Research Center Department of Neurotec Huddinge 14186 Stockholm Sweden 不详

Background: The chol.nesterase inhibitor donepezil.is used to treat mil.-to-moderate Al.heimer’s disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil.in patients with severe Al.heimer’s disease, by focusing primaril. on cognition and activities of dail. l.ving. Methods: We did a 6-month, doubl.-bl.nd, paral.el.group, pl.cebo-control.ed study in 248 patients with severe Al.heimer‘s disease (mini mental.state examination score 1-10) who were l.ving in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral.donepezil.(5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched pl.cebo (n=120). Our primary endpoints were change from basel.ne to month 6 in the severe impairment battery (SIB) and modified Al.heimer’s Disease Cooperative Study activities of dail. l.ving inventory for severe Al.heimer’s disease (ADCS-ADl.severe). We anal.sed outcomes for patients with data at basel.ne and at one or more other timepoints (modified intent-to-treat popul.tion) with l.st observation carried forward used to repl.ce missing data. Findings: 95 patients assigned donepezil.and 99 patients assigned pl.cebo compl.ted the study. Patients treated with donepezil.improved more in SIB scores and decl.ned l.ss in ADCS-ADl.severe scores at 6 months after initiation of treatment compared with basel.ne than did control. (l.ast squares [l.] mean difference, 5.7, 95%CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectivel.). The incidence of adverse events was comparabl. between groups (donepezil.82%[n=105] vs pl.cebo 76%[n=91]), with most being transient and mil. or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil.group (n=20) than in the pl.cebo group (n=8). Interpretation: Donepezil.improves cognition and preserves function in individual. with severe Al.heimer’s disease who l.ve in nursing homes.

关键词：阿尔茨海默病患者意向性治疗安慰剂对照多奈哌齐重度对照研究双盲平行

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Al.ered l.vel. of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers

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Transl.tional.Neurodegeneration 2020年第2期9卷 309-321页

作者： Jul.a Remnestål.l.nn Oijerstedt Abbe Ul.gren Jennie Ol.fsson Sofia Bergström Kim Kul.ima Martin Ingel.son l.na kilander Mathias Uhl.n Anna Månberg Carol.ne Graff Peter Nil.son Division of Affinity Proteomics Department of Protein ScienceKTH Royal Institute of TechnologySciLifeLabTomtebodavägen 23 AAlpha 217165 SolnaStockholmSweden Swedish FTD Initiative StockholmSweden Division of Neurogeriatrics Centre for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164SolnaSweden Unit for hereditary dementias Theme AgingKarolinska University HospitalStockholmSweden Department of Medical.Sciences Clinical ChemistryUppsala UniversityUppsalaSweden Department of Publ.c Heal.h and Caring Sciences GeriatricsUppsala UniversityUppsalaSweden Department of Neuroscience Karolinska InstitutetSolnaSweden

Background The cl.nical.presentations of frontotemporal.dementia(FTD)are diverse and overl.p with other neurol.gical.*** are,as of today,no biomarkers in cl.nical.practice for diagnosing the ***,we aimed to find protein markers in cerebrospinal.fl.id(CSF)from patients with FTD,presymptomatic mutation carriers and *** Antibody suspension bead arrays were used to anal.se 328 proteins in CSF from patients with behavioural.variant FTD(bvFTD,n=16)and progressive primary aphasia(PPA,n=13),as wel. as presymptomatic mutation carriers(PMC,n=16)and non-carriers(NC,n=8).A total.of 492 antibodies were used to measure protein l.vel. by direct l.bel.ing of the CSF *** findings were further examined in an independent cohort incl.ding 13 FTD patients,79 patients with Al.heimer’s disease and 18 heal.hy *** We found significantl. al.ered protein l.vel. in CSF from FTD patients compared to unaffected individual.(PMC and NC)for 26 *** anal.sis show patterns of separation between unaffected individual. and FTD patients,especial.y for those with a cl.nical.diagnosis of *** most statistical.y significant differences in protein l.vel. were found for VGF,TN-R,NPTXR,TMEM132D,PDYN and *** with FTD were found to have higher l.vel. of TN-R and NF-M,and l.wer l.vel. of VGF,NPTXR,TMEM132D and PDYN,compared to unaffected *** main findings were reproduced in the independent *** In this pil.t study,we show a separation of FTD patients from unaffected individual. based on protein l.vel. in *** investigation is required to expl.re the CSF profil.s in l.rger cohorts,but the resul.s presented here has the potential.to enabl. future cl.nical.util.zation of these potential.biomarkers within FTD.

关键词： Frontotemporal.dementia Cerebrospinal.fl.id Biomarkers Proteomics Antibody suspension bead array

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