Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
J Alzheimers Dis. 2019;68(4):1549-1559. doi: 10.3233/JAD-181243.
Biomarkers may soon be used to predict decline in older individuals. Extended follow-up studies are needed to determine the stability of such biomarker-based predictions.
To examine the long-term performance of baseline cognitive, neuroimaging, and cerebrospinal fluid (CSF) biomarker-assisted prognosis in patients with mild cognitive impairment.
Established, biomarker-defined, cohorts of subjects with mild cognitive impairment were examined for progression to dementia. Subjects with a baseline volumetric MRI, lumbar puncture, and Rey Auditory Verbal Learning Test were included. Dementia-free survival time in each biomarker-defined risk group was determined with Kaplan-Meier survival curves. The influence of each risk factor or combination of factors on dementia-free survival was examined with Cox proportional hazard analyses.
185 subjects were followed longitudinally for a mean (SD) 4.3 (2.8) years. 59% of participants converted within the follow-up period and the median dementia-free survival time was 2.8 years. Each individual risk factor predicted conversion to dementia (HR 1.9-3.7). The joint presence of any two risk factors increased risk for conversion (HR 7.1-11.0), with the presence of medial temporal atrophy and memory impairment showing the greatest risk for decline. Concordant atrophy, memory impairment, and abnormal CSF amyloid and tau was associated with the highest risk for conversion (HR 15.1). The presence of medial temporal atrophy was associated with the shortest dementia-free survival time, both alone and in combination with memory impairment, abnormal CSF amyloid and tau, or both.
These results suggest that baseline biomarker-assisted predictions of decline to dementia are stable over the long term, and that combinations of complementary biomarkers can improve the accuracy of these predictions.
生物标志物可能很快被用于预测老年人的衰退。需要进行扩展的随访研究，以确定此类基于生物标志物的预测的稳定性。
检查轻度认知障碍患者基线认知、神经影像学和脑脊液（CSF）生物标志物辅助预后的长期表现。
对轻度认知障碍患者进行了既定的、基于生物标志物的队列研究，以检查向痴呆的进展。纳入了基线容积 MRI、腰椎穿刺和 Rey 听觉言语学习测试的患者。使用 Kaplan-Meier 生存曲线确定每个生物标志物定义的风险组中无痴呆生存时间。使用 Cox 比例风险分析检查每个危险因素或危险因素组合对无痴呆生存的影响。
185 名患者平均（SD）随访 4.3（2.8）年。59%的参与者在随访期间发生转换，中位数无痴呆生存时间为 2.8 年。每个单独的危险因素都预测向痴呆的转化（HR 1.9-3.7）。任何两个危险因素的共同存在增加了向痴呆转化的风险（HR 7.1-11.0），内侧颞叶萎缩和记忆障碍的存在显示出最大的下降风险。一致的萎缩、记忆障碍以及异常的 CSF 淀粉样蛋白和 tau 与最高的转化风险相关（HR 15.1）。内侧颞叶萎缩的存在与无痴呆生存时间最短相关，无论是单独存在还是与记忆障碍、异常 CSF 淀粉样蛋白和 tau 或两者同时存在。
这些结果表明，基于生物标志物的衰退至痴呆的预测在长期内是稳定的，并且互补生物标志物的组合可以提高这些预测的准确性。
