Atrophy Rates in Asymptomatic Amyloidosis Implications for Alzheimer Prevention Trials.docVIP

AtrophyRatesinAsymptomaticAmyloidosis: ImplicationsforAlzheimerPreventionTrials K.AbigailAndrews1,2*,MarcModat1,2,KateE.Macdonald1,TomYeatman1,M.JorgeCardoso1,2, KelvinK.Leung1,2,JosephineBarnes1,VictorL.Villemagne3,ChristopherC.Rowe3,NickC.Fox1, SebastienOurselin1,2,JonathanM.Schott1,theAustralianImagingBiomarkers,LifestyleFlagshipStudy ofAgeing 1Dementia Research Centre (DRC), University College London, London, United Kingdom, 2Centre for Medical Image Computing (CMIC), University College London, London,UnitedKingdom,3AustinHealth,DepartmentofNuclearMedicineandCentreforPET,Heidelberg,Victoria,Australia Abstract ThereisconsiderableinterestindesigningtherapeuticstudiesofindividualsatriskofAlzheimerdisease(AD)topreventthe onset of symptoms. Cortical b-amyloid plaques, the first stage of AD pathology, can be detected invivo using positron emission tomography (PET), and several studies have shown that ,1/3 of healthy elderly have significant b-amyloid deposition.Hereweassessedwhetherasymptomaticamyloid-PET-positivecontrolshaveincreasedratesofbrainatrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age=73.567.3yrs; MMSE=2961.3) from the Australian Imaging Biomarkers Lifestyle study who had a baseline PittsburghCompoundB(PiB)PETscanandtwo3TMRIscans,18-monthsapart.WecalculatedPETstandarduptakevalue ratios(SUVR),andclassifiedindividualsasamyloid-positive/negative.Baselineand18-monthMRIscanswereregistered,and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of b-amyloid load correlated with hippocampal atrophy rate independent of age (p=0.014). Twenty-two (1/3) were PiB-positive (SUVR.1.40), the remaining 44 PiB-negative (SUVR#1.31). Compared to PiB-negatives, PiB-positive individualswereolder(76.867.5vs.71.767.5,p,0.05)andmorewereAPOE4positive(63.6%vs.19.2%,p,0.01)butthere were no differences in baseline brain, ventricle or hippocam