Brain Shape Changes Associated With Cerebral Atrophy in Healthy Aging and Alzheimer’s Disease

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.

Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes

“…The brain undergoes various morphological changes with aging, such as cerebral atrophy, gray and white matter changes (GM and WM, respectively), volume loss, ventricular enlargement, and sulci widening ( Blinkouskaya and Weickenmeier, 2021 ). It is widely known that the volume of the brain and its weight decreases with age at a rate of around 5% per decade after 40 years of age ( Peters, 2006 ).…”

“…In GM, cerebral atrophy occurs through morphological alterations related to a decrease in the complexity of dendrite arborization ( Blinkouskaya and Weickenmeier, 2021 ). Dendritic shortening, loss of dendritic shortening, and decreased dendritic spines trigger a progressive reduction in synaptic density and synaptic transmission, with major consequences on cognitive decline ( Dickstein et al, 2007 ).…”

“…During normal aging, the GM volume fraction has been reported to drop from 52.35% in those in their 40s to 50.49% in those in their 80s ( Taki et al, 2011 ). The WM has been reported to decrease from 47.63% in those in their 40s to 40.29% in those in their 80s, whereas the ventricular volume fraction increases from 3.22 to 5.66% ( Blinkouskaya and Weickenmeier, 2021 ). In addition, ventricular enlargement is caused by an increase in the space between folds and loss of gyrification ( Blinkouskaya and Weickenmeier, 2021 ).…”

3D finite-element brain modeling of lateral ventricular wall loading to rationalize periventricular white matter hyperintensity locations

“…Specifically, experimentally-informed constants of = 0.34 kPa and = 3.3 kPa for gray matter and = 0.68 kPa and = 6.6 kPa for white matter were chosen [56][57][58][59]. For simulations conducted here, lateral ventricle elements were removed from the models and the subarachnoid space was modeled as an ultrasoft compressible material with a Young's modulus of 1.0 Pa and a Poisson's ratio of 0.30 [60].…”

“…Ventricular enlargement is a hallmark feature of the aging brain and results from gradual white and gray matter atrophy [60,84]. Age-related ventricular volume growth is characterized by a mostly uniform expansion of the lateral ventricle [39,85].…”