Rate of β-amyloid accumulation varies with baseline amyloid burden: Implications for anti-amyloid drug trials.

Introduction: This study examined a longitudinal trajectory of β-amyloid (Aβ) accumulation at the predementia stage of Alzheimer's disease in the context of clinical trials.
Methods: Analyzed were baseline (BL) and 2 years' follow-up 18F-florbetapir positron emission tomography data of 246 Aβ-positive subjects with normal cognition and mild cognitive impairment. We studied the relationship between annual accumulation rates of 18F-florbetapir and BL standard uptake value ratios in whole gray matter (SUVR _GM ).
Results: Subjects with BL SUVR _GM of 0.56 to 0.92 (n = 134) appeared to accumulate Aβ approximately 1.5 times faster than remaining subjects. In subjects with SUVR _GM above 0.95, most regions with the highest annual accumulation rate were outside the established set of Alzheimer's disease typical regions.
Conclusion: There are global and regional variations in annual accumulation rate at the predementia stage of Alzheimer's disease. When taken into account, the sample size in anti-amyloid trials can be substantially reduced. Critically, treated and placebo groups should be matched for BL SUVR _GM .
(Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)