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Rate of β‐amyloid accumulation varies with baseline amyloid burden: Implications for anti‐amyloid drug trials
Author(s) -
Guo Tengfei,
Dukart Juergen,
Brendel Matthias,
Rominger Axel,
Grimmer Timo,
Yakushev Igor
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.05.013
Subject(s) - positron emission tomography , standardized uptake value , context (archaeology) , medicine , alzheimer's disease , placebo , amyloid (mycology) , β amyloid , cognitive decline , disease , pathology , nuclear medicine , biology , dementia , paleontology , alternative medicine
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 .