Identification of prognostic factors to predict cognitive decline of patients with early Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative study

INTRODUCTION: The objective of this study was to determine the factors including neuropsychological test performances and cerebrospinal fluid (CSF) biomarkers which can predict disease progression of early Alzheimer's disease (AD) in a Japanese population. METHODS: The group classification on early AD population in both Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and North American ADNI (NA-ADNI) was performed using the inclusion criteria including brain amyloid positivity on positron emission tomography or CSF. Participants with early AD from each cohort were stratified into two groups based on a cutoff 1.0 of Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) change at month 24 (m24): participants in “progress group” have CDR-SB change ≥ 1.0 and participants in “stable group” have CDR-SB change < 1.0. Then, we performed identification of prognostic factors from baseline items including neuropsychological scores (Assessment Scale-Cognitive Subscale[ADAS-cog 13], Mini-Mental State Examination (MMSE), CDR, FAQ, and Geriatric Depression Scale ), CSF markers (t-tau, p-tau, and beta-amyloid 1-42), vital signs (body weight, pulse rate, etc.,), by using two statistical approaches, Welch's t-test and simple linear regression by ordinary least squares. Comparisons between participants with J-ADNI and participants with NA-ADNI were also performed. RESULTS: Trends of CDR-SB changes were very similar between J-ADNI and NA-ADNI early AD population enrolled in this study. Baseline levels of CSF t-tau, p-tau, Mini-Mental State Examination, FAQ, and ADAS-cog13 were identified as prognostic factors in both J-ADNI and NA-ADNI. Based on a detailed subscale analysis on ADAS-cog13, four subscales (Q1: word recall, Q3: construction, Q4: delayed word recall, and Q8: word recognition) were identified as prognostic factors in both J-ADNI and NA-ADNI. DISCUSSION: Characterizing population with early AD can provide benefits for promoting efficiency in conducting AD clinical trials for disease-modifying treatments. Thus, implementing these prognostic factors into clinical trials may be potentially a good method to enrich participants with early AD who are suitable for evaluating treatment effects.