Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and cognitive testing obtained from cognitively normal individuals can be used to predict likelihood of progression to mild cognitive impairment several years later, for groups of individuals. However, it remains unclear whether these measures are useful for predicting likelihood of progression for an individual. The increasing focus on early intervention in clinical trials for Alzheimer’s disease emphasizes the importance of improving the ability to identify which cognitively normal individuals are more likely to progress over time, thus allowing researchers to efficiently screen participants, as well as determine the efficacy of any treatment intervention. The goal of this study was to determine which measures, obtained when individuals were cognitively normal, predict on an individual basis, the onset of clinical symptoms associated with a diagnosis of mild cognitive impairment due to Alzheimer’s disease. Cognitively normal participants (n = 224, mean baseline age = 57 years) were evaluated with a range of measures, including: cerebrospinal fluid amyloid-β and phosphorylated-tau, hippocampal and entorhinal cortex volume, cognitive tests scores and APOE genotype. They were then followed to determine which individuals developed mild cognitive impairment over time (mean follow-up = 11 years). The primary outcome was progression from normal cognition to the onset of clinical symptoms of mild cognitive impairment due to Alzheimer’s disease at 5 years post-baseline. Time-dependent receiver operating characteristic analyses examined the sensitivity and specificity of individual measures, and combinations of measures, as predictors of the outcome. Six measures, in combination, were the most parsimonious predictors of transition to mild cognitive impairment 5 years after baseline (area under the curve = 0.85; sensitivity = 0.80, specificity = 0.75). The addition of variables from each domain significantly improved the accuracy of prediction. The incremental accuracy of prediction achieved by adding individual measures or sets of measures successively to one another was also examined, as might be done when enrolling individuals in a clinical trial. The results indicate that biomarkers obtained when individuals are cognitively normal can be used to predict which individuals are likely to develop clinical symptoms at 5 years post-baseline. As a number of the measures included in the study could also be used as subject selection criteria in a clinical trial, the findings also provide information about measures that would be useful for screening in a clinical trial aimed at individuals with preclinical Alzheimer’s disease.

中文翻译：

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预测5岁个体从正常认知到轻度认知障碍的进展

最近的证据表明，从认知正常的人那里获得的脑脊液，MRI扫描和认知测验的测量值可用于预测数年后针对个人群体发展为轻度认知障碍的可能性。但是，尚不清楚这些措施是否可用于预测个体的进展可能性。对阿尔茨海默氏病临床试验中早期干预的日益关注强调了提高识别哪些认知正常个体更可能随着时间推移发展的能力的重要性，从而使研究人员能够有效地筛选参与者并确定任何治疗的功效干涉。这项研究的目的是确定当个体的认知正常时所获得的哪些量度，根据个人情况预测与诊断为阿尔茨海默氏病引起的轻度认知障碍相关的临床症状的发作。认知正常的参与者（n = 224，平均基线年龄= 57岁）通过一系列测量方法进行了评估，包括：脑脊液淀粉样蛋白β和磷酸化tau蛋白，海马和内嗅皮层体积，认知测验得分和APOE基因型。然后跟踪他们以确定哪些人随时间发展了轻度认知障碍（平均随访时间=11年）。主要结果是基线后5年从正常认知发展为阿尔茨海默氏病引起的轻度认知障碍的临床症状。随时间变化的接收器工作特性分析检查了单个度量以及度量组合作为结果预测指标的敏感性和特异性。基线后5年，六种量度的组合是过渡至轻度认知障碍的最简约的预测指标（曲线下面积= 0.85；敏感性= 0.80，特异性= 0.75）。来自每个域的变量的添加显着提高了预测的准确性。还研究了通过相继添加单个度量或一组度量而实现的预测的增量准确性，就像在临床试验中招募个人时所做的那样。结果表明，当个体认知正常时获得的生物标志物可用于预测基线后5年内哪些个体可能出现临床症状。由于研究中包括的许多措施也可以用作临床试验中的受试者选择标准，因此研究结果还提供了有关可用于针对临床前阿尔茨海默氏病患者进行临床试验筛查的措施的信息。