Biomarkers to Measure Treatment Effects in Alzheimers Disease What Should We Look for英文文献资料.docVIP

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Biomarkers to Measure Treatment Effects in Alzheimers Disease What Should We Look for英文文献资料.doc

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Biomarkers to Measure Treatment Effects in Alzheimers Disease What Should We Look for英文文献资料

SAGE-HindawiAccesstoResearch InternationalJournalofAlzheimer’sDisease Volume2011,ArticleID598175,4pages doi:10.4061/2011/598175 ReviewArticle BiomarkerstoMeasureTreatmentEffectsinAlzheimer’sDisease: WhatShouldWeLookfor? KennethRockwood DivisionofGeriatricMedicine,DalhousieUniversityandCentreforHealthCareoftheElderly,CapitalDistrictHealthAuthority, 1421-5955VeteransMemorialLane,Halifax,NS,CanadaB3H2E1 CorrespondenceshouldbeaddressedtoKennethRockwood,kenneth.rockwood@dal.ca Received6December2010;Revised11August2011;Accepted16August2011 AcademicEditor:GiovanniB.Frisoni Copyright?2011KennethRockwood.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Itisoftensurprisinglydi?culttotellwhetheratreatmentforAlzheimer’sdiseaseise?ective.Biomarkersmighto?erthepotential ofaquanti?ableobjectivemeasureoftreatmente?ectiveness.Thispapersuggestsseveralcriteriabywhichbiomarkersmightbe evaluatedasoutcomesmeasures.Theseincludebiologicalplausibility,statisticalsigni?cance,dosedependence,convergenceacross measures,andreplicability.Ifbiomarkerscanmeetthesecriteria,then,pendingregulatoryapproval,theymayhavearoleinthe evaluationoftreatmente?ectivenessinAlzheimer’sdisease.Ifnot,theirusefulnessmaybeinsupplementing,butnotsupplanting, clinicalpro?lesoftreatmente?ects. Foracompoundtobeademonstrablye?ectivetreatmentfor Alzheimer’sdiseasetwobroadconditionsmustbemet:?rst, the compound must be e?ective, and, second, it must be tested in a way which allows that e?ectiveness to be demonstrated.Asformidablydi?cultasthe?rstchallenge is,italsocanbesurprisinglytrickytoshowthatanytreat- ment for Alzheimer’s disease that falls short of cure o?ers therapeutic potential. Even the tried-and-true Alzheimer’s DiseaseAssessmentScale—CognitiveSubscale(ADAS-Cog) misclassi?es important clinical change—typically overesti- mating decline [1]—so that more than twenty years into themo