Frequency of preclinical Alzheimer’s disease in Japanese clinical study settings: A meta‐analysis

Abstract

AbstractBackgroundUnderstanding the accurate frequency of preclinical Alzheimer’s disease (AD), those with positive evidence of amyloid accumulation in brain but without significant cognitive decline, is an important basis of conducting clinical trials for the development of disease‐modifying therapies for AD. Many of earlier studies reporting the frequency of preclinical AD among cognitive normal (CN) individuals have based on the clinical study cohort from Western countries (e.g., 38% in ADNI cohort or 33% in AIBL cohort), and the evidence about the frequency in Asian country cohorts is limited. In Japan, J‐ADNI cohort is one of the few cohorts that published the frequency of preclinical AD: it was 23% in J‐ADNI, to be lower than in ADNI or AIBL. The potential region‐specific difference in the frequency of preclinical AD may have influence on the required number of participants to recruit to AD clinical trials. In this study, we aim to estimate the frequency of preclinical AD in the clinical study settings in Japan, using meta‐analysis by incorporating some additional unpublished Japanese cohort study data.MethodWe reviewed earlier literatures reporting frequency of preclinical AD among CN (CDR‐global = 0) participants, and also reviewed the original data of 4 Japanese cohort study (i.e., AMED‐Preclinical, Brain/Minds Aging Imaging Study, J‐ADNI, and A4 study screening conducted in Japan), and included those who were diagnosed as CN (CDR = 0) at the study participation. These cohort data were meta‐analyzed with random‐effect model.ResultIn total, 238 CN participants in 5 different groups were evaluated, and among them 44 turned out to be amyloid positive. The overall frequency of preclinical AD (of any stage) was estimated as 18% (95% CI: 13‐23%), with the low statistical heterogeneity of I2 = 0% (as plotted on a forest plot in Figure). In meta‐regression while incorporating 14 earlier literature data, being the Japanese cohort had no association with the frequency of preclinical AD (p = 0.305).ConclusionIn the current meta‐analysis, there were no evidence to suggest the frequency of preclinical AD in clinical study settings of Japan is different from that of Western countries.