AbstractIntroductionWe conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J‐ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America.MethodsA total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography‐ or cerebrospinal fluid amyloid β(1–42)‐positive LMCI and mild AD between J‐ADNI and ADNI.ResultsAmyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J‐ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid‐positive LMCI in J‐ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J‐ADNI (n = 73) compared with ADNI (n = 230).DiscussionThese results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries.
Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons
IntroductionLittle is known about the utility of plasma amyloid beta (Aβ) in clinical trials of Alzheimer's disease (AD).MethodsWe analyzed longitudinal plasma samples from two large multicenter clinical trials: (1) donezepil and vitamin E in mild cognitive impairment (n = 405, 24 months) and (2) simvastatin in mild to moderate AD (n = 225, 18 months).ResultsBaseline plasma Aβ was not related to cognitive or clinical progression. We observed a decrease in plasma Aβ40 and 42 among apolipoprotein E epsilon 4 (APOE ε4) carriers relative to noncarriers in the mild cognitive impairment trial. Patients treated with simvastatin showed a significant increase in Aβ compared with placebo. We found significant storage time effects and considerable plate‐to‐plate variation.DiscussionWe found no support for the utility of plasma Aβ as a prognostic factor or correlate of cognitive change. Analysis of stored specimens requires careful standardization and experimental design, but plasma Aβ may prove useful in pharmacodynamic studies of antiamyloid drugs.