Brain Shape Changes Associated With Cerebral Atrophy in Healthy Aging and Alzheimer's Disease
Brain Shape Changes Associated With Cerebral Atrophy in Healthy Aging and Alzheimer's Disease
复制标题
DOI：
10.3389/fmech.2021.705653
复制
发表时间：
2021-07-19
影响因子：
2.3
通讯作者：
Weickenmeier, Johannes
中科院分区：
文献类型：
--
作者：
Blinkouskaya, Yana;Weickenmeier, Johannes
健康和病理性脑老化的特征都是不同程度的认知能力下降，这与被称为脑萎缩的形态学变化密切相关。这些标志性形态变化包括皮质变薄、白色和灰质体积损失、心室扩大以及脑回丧失，所有这些都是由无数亚细胞和细胞衰老过程引起的。虽然大脑老化的生物学已经被广泛研究，但大脑老化的机制仍然远远不够。在这里，我们提出了一个多物理模型，耦合组织萎缩和阿尔茨海默病生物标志物的进展。我们采用乘法分裂的变形梯度收缩和弹性的一部分。我们将萎缩建模为区域特异性各向同性收缩，并区分健康老龄化中恒定的组织依赖性萎缩率和阿尔茨海默病中与局部生物标志物浓度成比例的萎缩率。我们的有限元建模方法提供了一个计算框架，系统地研究脑萎缩的时空进展及其对大脑形状的区域影响。我们通过与横断面医学影像学研究的比较来验证我们的结果，这些研究揭示了持续的年龄相关性萎缩模式。我们的长期目标是开发一种诊断工具，能够区分健康和加速老化，通常在阿尔茨海默病和相关痴呆症中观察到，以便更早和更有效地干预。
Both healthy and pathological brain aging are characterized by various degrees of cognitive decline that strongly correlate with morphological changes referred to as cerebral atrophy. These hallmark morphological changes include cortical thinning, white and gray matter volume loss, ventricular enlargement, and loss of gyrification all caused by a myriad of subcellular and cellular aging processes. While the biology of brain aging has been investigated extensively, the mechanics of brain aging remains vastly understudied. Here, we propose a multiphysics model that couples tissue atrophy and Alzheimer's disease biomarker progression. We adopt the multiplicative split of the deformation gradient into a shrinking and an elastic part. We model atrophy as region-specific isotropic shrinking and differentiate between a constant, tissue-dependent atrophy rate in healthy aging, and an atrophy rate in Alzheimer's disease that is proportional to the local biomarker concentration. Our finite element modeling approach delivers a computational framework to systematically study the spatiotemporal progression of cerebral atrophy and its regional effect on brain shape. We verify our results via comparison with cross-sectional medical imaging studies that reveal persistent age-related atrophy patterns. Our long-term goal is to develop a diagnostic tool able to differentiate between healthy and accelerated aging, typically observed in Alzheimer's disease and related dementias, in order to allow for earlier and more effective interventions.