Identification of prognostic factors to predict cognitive decline of patients with early Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative study
Identification of prognostic factors to predict cognitive decline of patients with early Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative study
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日本阿尔茨海默病神经影像倡议研究中确定预测早期阿尔茨海默病患者认知能力下降的预后因素
DOI：
10.1016/j.trci.2019.06.004
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发表时间：
2019
影响因子：
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通讯作者：
Japanese Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
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作者：
Yagi Takuya;Kanekiyo Michio;Ito Junichi;Ihara Ryoko;Suzuki Kazushi;Iwata Atsushi;Iwatsubo Takeshi;Aoshima Ken;Alzheimer's Disease Neuroimaging Initiative;Japanese Alzheimer's Disease Neuroimaging Initiative
本研究的目的是确定在日本人群中预测早期阿尔茨海默病(AD)疾病进展的因素，包括神经心理测试成绩和脑脊液(CSF)生物标志物。方法以日本阿尔茨海默病神经成像倡议(J-ADNI)和北美ADNI(NA-ADNI)的脑淀粉样蛋白阳性为纳入标准，对早期AD人群进行分组。每个队列中早期AD的参与者根据第24个月(M24)临床痴呆评定量表总和变化的截止点1.0被分层为两组：“进展组”参与者的≥变化为1.0，而“稳定组”的参与者的CDR-SB变化为1.0。然后，我们从基线项目中识别预后因素，包括神经心理评分(评估量表-认知子量表[ADAS-cog 13]、简易智力状态检查(MMSE)、CDR、FAQ和老年抑郁量表)、脑脊液标志物(t-tau、p-tau和β-淀粉样蛋白1-42)、生命体征(体重、脉率等)，使用两种统计方法，韦尔奇t检验和普通最小二乘的简单线性回归。结果纳入本研究的J-ADNI和NA-ADNI早期AD人群CDR-SB变化趋势非常相似。脑脊液中t-tau、p-tau、简易智力状态检查、FAQ和ADAS-cog13的基线水平被确定为J-ADNI和NA-ADNI的预后因素。基于对ADAS-cog13的详细子量表分析，四个子量表(Q1：单词回忆，Q3：建构，Q4：延迟单词回忆，Q8：单词再认)被确定为J-ADNI和NA-ADNI的预后因素。因此，将这些预后因素应用到临床试验中，可能是一种潜在的很好的方法来丰富适合评估治疗效果的早期AD患者。
IntroductionThe 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.MethodsThe 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.ResultsTrends 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.DiscussionCharacterizing 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.