. Japanese and North American Alzheimer’s Disease Neuroimaging Initiative studies: Harmonization for international trials. Alzheimers Dement. 2018 May 9.


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  1. The results of this paper by Itwatsubo et al. comparing baseline characteristics and longitudinal clinical outcomes of late MCI and mild AD between JADNI and ADNI are important to those who are designing clinical trials that cover the spectrum of early AD. The weakness of this designated distinction between late MCI and mild AD, is that it is clinically but not biologically determined. The defining criteria that were used overlapped considerably in MMSE range (24-30 for LMCI vs 20-26 for mild AD), in CDR stages (0.5 for LMCI and mild AD and 1.0 for mild AD) and in their defined episodic memory impairment.  Nevertheless, it is apparent that despite the overlap, the defined mild AD group differed significantly in ADNI versus JADNI, with JADNI enrolling a more mildly impaired population who declined more slowly on cognitive, global, and functional measures. As this applies to clinical trials and the potential for pooling of data, these results suggest that caution is in order. Care should be given in the randomization approach to early AD trials, particularly in stratifying broadly defined study populations of early AD, which includes LMCI and mild AD. Modelling with effect sizes determined from stratified subgroups and balancing recruitment by a severity stratification factor such as CDR 0.5 and CDR 1.0 could help address these findings. Additionally it would be best to investigate treatment by severity interaction in early phase trials before undertaking a large inclusive later stage trial.

    View all comments by Howard Feldman
  2. The results of the JADNI project have given us a wealth of information. In particular, the very similar progress of MCI in Japan and the United States shows that Alzheimer’s disease might be fundamentally different from conventional diseases.

    In the past, there were far fewer Alzheimer patients. Therefore, Alzheimer’s may be described as a phenomenon created by increased longevity, apart from some rare exceptions such as juvenile Alzheimer’s. If Alzheimer’s is caused by aging, it is important that we diagnose the symptoms early and respond appropriately. Furthermore, unlike conventional diseases, Alzheimer’s may be caused by various factors being mutually related at the same time.

    An important contribution to the study of AD, the JADNI project made it possible to effectively gather research data worldwide by providing a standard for data quality. For future research, accurately grasping the symptoms related to this multifactorial disease and performing multiple analyses will be indispensable. From this point of view, future Japanese research is expected to greatly contribute to the world in terms of collecting high-quality data on multiple factors and performing multi-analysis using artificial intelligence.

    View all comments by Yoshihide Esaki

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  1. Japanese ADNI Data Parallel North American ADNI, Encouraging Global Trials