Amyloid status imputed from a multimodal classifier including structural MRI distinguishes progressors from nonprogressors in a mild Alzheimer's disease clinical trial cohort.
Mild-Alzheimer's disease (AD) subjects without significant Aβ pathology represent a confounding finding for clinical trials because they may not progress clinically on the expected trajectory, adding variance into analyses where slowing of progression is being measured.



A prediction model based on structural magnetic resonance imaging (MRI) in combination with baseline demographics and clinical measurements was used to impute Aβ status of a placebo-treated mild-AD sub-cohort (N = 385) of patients participating in global phase 3 trials. The clinical trajectories of this cohort were evaluated over 18 months duration of the trial, stratified by imputed Aβ status within a mixed-model repeated measures statistical framework.



In the imputed Aβ-positive cohort, both cognitive (ADAS-Cog14 and MMSE) and functional (ADCS-iADL) measures declined more rapidly than in the undifferentiated population.



Our results demonstrate imputing Aβ status from MRI scans in mild-AD subjects may be a useful screening tool in global clinical trials if amyloid measurement is not available.
Department Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA, USA. Electronic address: duygu.tosun@ucsf.edu.
Duygu
D
Tosun
Eli Lilly and Company, Indianapolis, IN, USA.
Yun-Fei
YF
Chen
Eli Lilly and Company, Indianapolis, IN, USA.
Peng
P
Yu
Eli Lilly and Company, Indianapolis, IN, USA.
Karen L
KL
Sundell
BioClinica, CA, USA.
Joyce
J
Suhy
Eli Lilly and Company, Indianapolis, IN, USA.
Eric
E
Siemers
Eli Lilly and Company, Indianapolis, IN, USA.
Adam J
AJ
Schwarz
Department Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA, USA.
Michael W
MW
Weiner
D000368:Aged; D000544:Alzheimer Disease / Q000145:classification* / Q000000981:diagnostic imaging* / Q000628:therapy; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005026:Ethylene Glycols; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D000073216:Mental Status and Dementia Tests; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index
D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir
ADAS-Cog14; ADCS-iADL; Alzheimer's disease; Aβ pathology; Aβ-positivity; Clinical decline; Florbetapir PET; MMSE; Structural MRI