Abstract
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.
Highlights
Brain aging is characterized by a myriad of biological, chemical, and mechanical hallmark features
We propose a constitutive model for the evolution of the atrophy measure θ that allows to differentiate between healthy brain aging and accelerated aging observed in many neurodegenerative diseases such as Alzheimer’s disease (AD) (Weickenmeier et al, 2018; Schäfer et al, 2019)
We evaluate our simulations with respect to hallmark features of cerebral atrophy and aim at identifying key differences between healthy brain aging and accelerated aging associated with AD
Summary
Brain aging is characterized by a myriad of biological, chemical, and mechanical hallmark features. While biological and chemical aging processes have been studied for decades, the mechanical aspects of brain aging remain understudied (Raz and Rodrigue, 2006; Hall et al, 2020). While healthy brain aging is characterized by these changes, neurodegenerative diseases, such as Alzheimer’s disease (AD) and related dementias, exhibit a significant acceleration of brain aging mechanisms that cause a noticeable divergence from the healthy atrophy trajectory observed in cross-sectional studies (Coupé et al, 2019). The changes in the aging brain become so pervasive that they are clearly
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