Tengfei Guo1, Juergen Dukart2, Matthias Brendel3, Axel Rominger4, Timo Grimmer5, Igor Yakushev6. 1. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: tengfei.guo@berkeley.edu. 2. F. Hoffmann-La Roche, Pharma Research Early Development, Roche Innovation Centre Basel, Basel, Switzerland. 3. Department of Nuclear Medicine, Ludwig-Maximilians-Universität München, Munich, Germany. 4. Department of Nuclear Medicine, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland. 5. Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 6. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Abstract
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.
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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