THE ANTI-AMYLOID TREATMENT IN ASYMPTOMATIC ALZHEIMER'S DISEASE (A4) STUDY: REPORT OF SCREENING DATA RESULTS

Abstract

The A4 Study is a secondary prevention trial of an anti-amyloid antibody in clinically normal (CN) individuals age 65-85 with elevated brain amyloid on screening PET scan. Here we report the demographic, cognitive, APOE genotype and amyloid PET data from the A4 screening process. CN participants (CDR=0; MMSE 25-30) were screened at 67 centers in the United States, Canada, Australia, and Japan. Screening assessments obtained prior to Amyloid PET imaging included cognitive testing with the Preclinical Alzheimer Cognitive Composite (PACC), a participant and study partner reported functional assessment, the Cognitive Function Index (CFI), and APOE genotyping. A quantitative SUVr/visual read algorithm of 18F-Florbetapir Amyloid PET classified participants as Elevated Amyloid (Aβ+), eligible to continue in screening, or Not Elevated (Aβ-). 6762 participants (14% minority) were screened. Amyloid PET was acquired on 4487 participants, with 1323 (29.5%) classified as Aβ+ (mean SUVr=1.33±0.18). Aβ+ participants were slightly older than Aβ-, with no differences in sex, education, marital or retirement status (Table 1). Minority participants across multiple races were less likely to be Aβ+. Aβ+ were more likely to have a family history of dementia (74% Aβ+ vs. 68% Aβ-) and more likely to carry at least one APOEε4 allele (58% Aβ+ vs. 25% Aβ-). Aβ+ showed worse performance on screening PACC (p< 0.0001, adjusted for age, gender, and education; Table 2). Aβ+ participants and their study partners reported higher scores on CFI (p<0.0001). A4 completed enrollment in December 2017 with 1169 Aβ+ randomized participants. Aβ+ participants eligible for the A4 Study show similar demographic characteristics to AD dementia populations with nearly 60% APOEε4 carriers. Despite the relatively narrow range of normal cognitive performance required for A4 eligibility, Aβ+ performed significantly lower on screening cognitive tests and had higher rates of self- and study partner-reported cognitive functional decline. The A4 Study demonstrates the feasibility of enrolling a preclinical AD population in a large prevention trial that will test whether an anti-amyloid agent can slow cognitive decline during the preclinical stage of AD.