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

Guo, Tengfei; Dukart, Juergen; Brendel, Matthias; Rominger, Axel Oliver; Grimmer, Timo; Yakushev, Igor (2018). Rate of β-amyloid accumulation varies with baseline amyloid burden: Implications for anti-amyloid drug trials. Alzheimer's & dementia, 14(11), pp. 1387-1396. Elsevier 10.1016/j.jalz.2018.05.013

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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 (SUVRGM).
RESULTS:
Subjects with BL SUVRGM of 0.56 to 0.92 (n = 134) appeared to accumulate Aβ approximately 1.5 times faster than remaining subjects. In subjects with SUVRGM 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 SUVRGM.

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