Abstract Details

Title Simple risk scores for the prediction of brain ß-amyloid and tau status in older adults with mild cognitive impairment

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-003

Background Targeting Aβ and tau pathology, have been the primary strategy in recent clinical trials for Alzheimer’s disease (AD). As therapies targeting Aβ and tau emerge, as exemplified Aducanumab, identifying persons likely to be biomarker positive can facilitate patient selection for biomarker testing.

Objective To demonstrate the feasibility of developing simple risk scores for predicting amyloid beta (Aβ) and tau status among individuals with mild cognitive impairment (MCI).

Design/Methods Participants were 447 individuals with MCI from the ADNI data-set. The sample was randomly divided into training (67%) and test (33%) sets. Biomarker status was defined based on the gold standard of Aβ and tau PET. A machine learning-based approach was used to develop risk scores in the training set. Performance of models were validated on the test set. Multiple risk score models were developed for both Aβ and tau positivity based on a hierarchical combination of categories of predictors including demographics, neuropsychological assessment, APOE4 status, and MRI measures.

Results The highest AUC for predicting Aβ positivity was 0.79 (sensitivity=69.0%, specificity=80.8%), which was achieved with a model that included age, ADAS-Cog 13 score, APOE4 genotype, and the presence of white matter hyperintensities. The best model for prediction of tau positivity included age, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), Trail Making Test B, and functional activities questionnaire (FAQ) scores, APOE4 alleles, binarized abnormal hippocampal volume variable (AUC=0.87, sensitivity=84.6%, specificity=86.8%). A sensitivity analysis showed that addition of binary Aβ status modestly improved performance of models predicting tau positivity (AUC=0.91, sensitivity=84.6%, specificity=89.8%).

Conclusions Simple risk scores using easily obtainable data could be used for predicting Aβ and tau positivity in individuals with MCI as a strategy for targeting individuals for more costly or invasive PET or CSF based biomarker assessment.

Authors/Disclosures
Ali Ezzati, MD (University of California, Irvine) PRESENTER	Dr. Ezzati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mist Research. Dr. Ezzati has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioDelivery Sciences International (BDSI) . The institution of Dr. Ezzati has received research support from NIA. The institution of Dr. Ezzati has received research support from Alzheimer's Association. The institution of Dr. Ezzati has received research support from Cure Alzheimer's Fund.
Richard B. Lipton, MD, FAAN (Albert Einstein College of Medicine)	Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Pfizer. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axon. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cool Tech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BDSI. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. Dr. Lipton has stock in Axon. Dr. Lipton has stock in CoolTech. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from Veterans Administration. Dr. Lipton has received publishing royalties from a publication relating to health care.
Kellen Petersen (Albert Einstein College of Medicine)	No disclosure on file