Mayblyum Danielle V, Becker J Alex, Jacobs Heidi I L, Buckley Rachel F, Schultz Aaron P, Sepulcre Jorge, Sanchez Justin S, Rubinstein Zoe B, Katz Samantha R, Moody Kirsten A, Vannini Patrizia, Papp Kathryn V, Rentz Dorene M, Price Julie C, Sperling Reisa A, Johnson Keith A, Hanseeuw Bernard J
From the Department of Radiology (D.V.M., J.A.B., H.I.L.J., J.S., J.S.S., Z.B.R., S.R.K., K.A.M., J.C.P., K.A.J., B.J.H.), Massachusetts General Hospital, Gordon Center for Medical Imaging and Athinoula A. Martinos Center for Biomedical Imaging, Boston; Faculty of Health, Medicine and Life Sciences (H.I.L.J.), School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, the Netherlands; Department of Neurology (R.F.B., P.V., K.V.P., D.M.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School, Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston; The Florey Institute (R.F.B.) and Melbourne School of Psychological Science (R.F.B.), University of Melbourne, Victoria Australia; Department of Neurology (A.P.S., B.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; and Department of Neurology (B.J.H.), Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Neurology. 2021 Jun 14;96(24):e2933-e2943. doi: 10.1212/WNL.0000000000012108.
To compare how structural MRI, fluorodeoxyglucose (FDG), and flortaucipir (FTP) PET signals predict cognitive decline in high-amyloid vs low-amyloid participants with the goal of determining which biomarker combination would result in the highest increase of statistical power for prevention trials.
In this prospective cohort study, we analyzed data from clinically normal adults from the Harvard Aging Brain Study with MRI, FDG, FTP, and Pittsburgh compound B (PiB)-PET acquired within a year and prospective cognitive evaluations over a mean 3-year follow-up. We focused analyses on predefined regions of interest: inferior temporal, isthmus cingulate, hippocampus, and entorhinal cortex. Cognition was assessed with the Preclinical Alzheimer's Cognitive Composite. We evaluated the association between biomarkers and cognitive decline using linear mixed-effect models with random intercepts and slopes, adjusting for demographics. We generated power curves simulating prevention trials.
Data from 131 participants (52 women, age 73.98 ± 8.29 years) were analyzed in the study. In separate models, most biomarkers had a closer association with cognitive decline in the high-PiB compared to the low-PiB participants. A backward stepwise regression including all biomarkers demonstrated that only neocortical PiB, entorhinal FTP, and entorhinal FDG were independent predictors of subsequent cognitive decline. Power analyses revealed that using both high PiB and low entorhinal FDG as inclusion criteria reduced 3-fold the number of participants needed in a hypothetical trial compared to using only high PiB.
In preclinical Alzheimer disease, entorhinal hypometabolism is a strong and independent predictor of subsequent cognitive decline, making FDG a potentially useful biomarker to increase power in clinical trials.
This study provides Class II evidence that in people with preclinical Alzheimer disease, entorhinal hypometabolism identified by FDG-PET is predictive of subsequent cognitive decline.
比较结构磁共振成像（MRI）、氟脱氧葡萄糖（FDG）和氟他西匹（FTP）正电子发射断层扫描（PET）信号如何预测高淀粉样蛋白与低淀粉样蛋白参与者的认知衰退，目的是确定哪种生物标志物组合能使预防试验的统计效力得到最大程度的提高。
在这项前瞻性队列研究中，我们分析了来自哈佛衰老大脑研究的临床正常成年人的数据，这些数据包括在一年内进行的MRI、FDG、FTP和匹兹堡化合物B（PiB）-PET检查，以及平均为期3年随访的前瞻性认知评估。我们将分析重点放在预定义的感兴趣区域：颞下回、扣带回峡部、海马体和内嗅皮质。使用临床前阿尔茨海默病认知综合量表评估认知情况。我们使用具有随机截距和斜率的线性混合效应模型评估生物标志物与认知衰退之间的关联，并对人口统计学因素进行校正。我们生成了模拟预防试验的效力曲线。
本研究分析了131名参与者（52名女性，年龄73.98±8.29岁）的数据。在单独的模型中，与低PiB参与者相比，大多数生物标志物与高PiB参与者的认知衰退关联更为密切。一项纳入所有生物标志物的向后逐步回归分析表明，只有新皮质PiB、内嗅FTP和内嗅FDG是后续认知衰退的独立预测因子。效力分析显示，与仅使用高PiB相比，将高PiB和低内嗅FDG都作为纳入标准可使假设试验所需的参与者数量减少两倍。
在临床前阿尔茨海默病中，内嗅代谢减退是后续认知衰退的一个强有力的独立预测因子，这使得FDG成为提高临床试验效力的一个潜在有用的生物标志物。
本研究提供了II类证据，即在临床前阿尔茨海默病患者中，FDG-PET识别出的内嗅代谢减退可预测后续的认知衰退。
