常染色体显性阿尔茨海默病的皮质双相宏观和微观结构变化。
Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease.
机构信息
Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
出版信息
Alzheimers Dement. 2021 Apr;17(4):618-628. doi: 10.1002/alz.12224. Epub 2020 Nov 16.
INTRODUCTION
A biphasic model for brain structural changes in preclinical Alzheimer's disease (AD) could reconcile some conflicting and paradoxical findings in observational studies and anti-amyloid clinical trials.
METHODS
In this study we tested this model fitting linear versus quadratic trajectories and computed the timing of the inflection points vertexwise of cortical thickness and cortical diffusivity-a novel marker of cortical microstructure-changes in 389 participants from the Dominantly Inherited Alzheimer Network.
RESULTS
In early preclinical AD, between 20 and 15 years before estimated symptom onset, we found increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later preclinical and symptomatic stages. The inflection points 16 to 19 years before estimated symptom onset are in agreement with the start of tau biomarker alterations.
DISCUSSION
These findings confirm a biphasic trajectory for brain structural changes and have direct implications when interpreting magnetic resonance imaging measures in preventive AD clinical trials.
简介
在临床前阿尔茨海默病（AD）的脑结构变化中存在双相模型，可以调和观察性研究和抗淀粉样蛋白临床试验中的一些矛盾和悖论发现。
方法
在这项研究中，我们测试了线性和二次轨迹的模型拟合，并计算了皮质厚度和皮质弥散度（皮质微结构变化的新标志物）的拐点在 389 名来自显性遗传性阿尔茨海默病网络的参与者中的顶点位置。
结果
在临床前 AD 的早期，在估计症状出现前 20 到 15 年，我们发现皮质厚度增加，皮质弥散度降低，随后在临床前和症状阶段出现皮质变薄和皮质弥散度增加。在估计症状出现前 16 到 19 年的拐点与 tau 生物标志物改变的开始时间一致。
讨论
这些发现证实了脑结构变化的双相轨迹，当在预防 AD 临床试验中解释磁共振成像测量结果时具有直接意义。
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