Predicting progression from normal cognition to mild cognitive impairment for individuals at 5 years
Predicting progression from normal cognition to mild cognitive impairment for individuals at 5 years
复制标题
DOI：
10.1093/brain/awx365
复制
发表时间：
2018-03-01
期刊：
影响因子：
14.5
通讯作者：
Wang, Mei-Cheng
中科院分区：
文献类型：
--
作者：
Albert, Marilyn;Zhu, Yuxin;Wang, Mei-Cheng
最近的证据表明，从认知正常个体获得的脑脊液，MRI扫描和认知测试的测量可用于预测几年后进展为轻度认知障碍的可能性。然而，目前尚不清楚这些措施是否有助于预测个人进展的可能性。对阿尔茨海默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有可能随着时间的推移而进展的能力的重要性，从而使研究人员能够有效地筛选参与者，以及确定任何治疗干预的有效性。本研究的目的是确定当个体认知正常时获得的哪些措施，在个体基础上预测与阿尔茨海默病所致轻度认知障碍诊断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）进行了一系列的措施，包括：脑脊液淀粉样蛋白-b和磷酸化tau，海马和内嗅皮质体积，认知测试评分和APOE基因型。然后对他们进行随访，以确定哪些人随着时间的推移出现轻度认知障碍（平均随访时间= 11年）。主要结局是基线后5年时从正常认知进展至阿尔茨海默病所致轻度认知障碍的临床症状发作。时间依赖性受试者操作特征分析检查了个体测量的敏感性和特异性，以及测量组合作为结果的预测因子。六项指标相结合，是基线后5年转变为轻度认知障碍的最简约预测因素（曲线下面积= 0.85;敏感性= 0.80，特异性= 0.75）。从每个域的变量的添加显着提高了预测的准确性。还检查了通过连续添加单个测量或测量集来实现的预测的增量准确性，正如在临床试验中招募个体时可能会做的那样。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哪些个体可能在基线后5年出现临床症状。由于研究中包括的许多措施也可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措施的信息，这些措施可用于针对临床前阿尔茨海默病患者的临床试验中的筛查。
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-b 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.