Department of Biomedical Engineering, Columbia University, New York, NY, United States of America.
Department of Psychiatry, Columbia University, New York, NY, United States of America.
PLoS One. 2020 Jul 29;15(7):e0234255. doi: 10.1371/journal.pone.0234255. eCollection 2020.
'Normal aging' in the brain refers to age-related changes that occur independent of disease, in particular Alzheimer's disease. A major barrier to mapping normal brain aging has been the difficulty in excluding the earliest preclinical stages of Alzheimer's disease. Here, before addressing this issue we first imaged a mouse model and learn that the best MRI measure of dendritic spine loss, a known pathophysiological driver of normal aging, is one that relies on the combined use of functional and structural MRI. In the primary study, we then deployed the combined functional-structural MRI measure to investigate over 100 cognitively-normal people from 20-72 years of age. Next, to cover the tail end of aging, in secondary analyses we investigated structural MRI acquired from cognitively-normal people, 60-84 years of age, who were Alzheimer's-free via biomarkers. Collectively, the results from the primary functional-structural study, and the secondary structural studies revealed that the dentate gyrus is a hippocampal region differentially affected by aging, and that the entorhinal cortex is a region most resistant to aging. Across the cortex, the primary functional-structural study revealed and that the inferior frontal gyrus is differentially affected by aging, however, the secondary structural studies implicated other frontal cortex regions. Together, the results clarify how normal aging may affect the brain and has possible mechanistic and therapeutic implications.
大脑中的“正常衰老”是指与疾病无关的与年龄相关的变化，特别是阿尔茨海默病。绘制正常大脑衰老图谱的主要障碍一直是难以排除阿尔茨海默病的最早临床前阶段。在这里，在解决这个问题之前，我们首先对小鼠模型进行了成像，并了解到树突棘丢失的最佳 MRI 测量方法，树突棘丢失是正常衰老的已知病理生理学驱动因素之一，该方法依赖于功能和结构 MRI 的联合使用。在主要研究中，我们随后部署了联合功能-结构 MRI 测量方法，对 20-72 岁的 100 多名认知正常的人进行了调查。接下来，为了涵盖衰老的末端，在二次分析中，我们调查了通过生物标志物证明无阿尔茨海默病的 60-84 岁认知正常的人的结构 MRI。总的来说，主要的功能-结构研究以及次要的结构研究结果表明，齿状回是受衰老影响不同的海马区域，而内嗅皮层是最能抵抗衰老的区域。在整个大脑皮层中，主要的功能-结构研究表明，下额回受到衰老的影响不同，但是，次要的结构研究涉及到其他额叶皮层区域。总之，这些结果阐明了正常衰老如何影响大脑，并具有可能的机制和治疗意义。
