Rates of Decline in Alzheimer Disease Decrease with Age 英文参考文献.docVIP

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Rates of Decline in Alzheimer Disease Decrease with Age 英文参考文献.doc

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Rates of Decline in Alzheimer Disease Decrease with Age 英文参考文献

RatesofDeclineinAlzheimerDiseaseDecreasewithAge DominicHolland1*,RahulS.Desikan2,AndersM.Dale1,2,LindaK.McEvoy2,fortheAlzheimer’sDisease NeuroimagingInitiative 1DepartmentofNeurosciences,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2DepartmentofRadiology,UniversityofCaliforniaSan Diego,LaJolla,California,UnitedStatesofAmerica Abstract AgeisthestrongestriskfactorforsporadicAlzheimerdisease(AD),yettheeffectsofageonratesofclinicaldeclineand brainatrophyinADhavebeenlargelyunexplored.Here,weexaminedlongitudinalratesofchangeasafunctionofbaseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90years (total n=723). The effect of age was modeledusingmixedeffectslinearregression.Therewaspronouncedreductioninratesofclinicaldeclineandatrophywith ageforADandMCIindividuals,whereasHCsshowedincreasedratesofclinicaldeclineandatrophywithage.Thisresulted inconvergenceinratesofchangeforHCsandpatientswithadvancingageforseveralmeasures.Baselinecerebrospinal fluiddensitiesofAD-relevantproteins,Ab1–42,tau,andphospho-tau181p (ptau),showedasimilarpatternofconvergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicatinguniformityofclinicalseverityatbaseline.TheseresultsimplythatthephenotypicexpressionofADisrelatively mildinindividualsolderthanapproximately85years,andthismayaffecttheabilitytodistinguishADfromnormalagingin theveryold. Ourfindings showthat inclusionof olderindividuals in clinical trialswill substantially reduce thepower to detectdisease-modifyingtherapeuticeffects,leadingtodramaticincreasesinrequiredclinicaltrialsamplesizeswithageof studysample. Citation:HollandD,DesikanRS,DaleAM,McEvoyLK,fortheAlzheimer’sDiseaseNeuroimagingInitiative(2012)RatesofDeclineinAlzheimerDiseaseDecrease withAge.PLoSONE7(8):e42325.doi:10.1371/journal.p