Back to search

FRINATEK-Fri prosj.st. mat.,naturv.,tek

Towards a mathematical model and a computational framework of the physical processes leading to Alzheimers disease

Alternative title: Mot matematiske og beregningsorienterte rammeverk for å forstå de fysiske prosessene bak Alzheimers sykdom

Awarded: NOK 10.9 mill.

Project Number:

301013

Application Type:

Project Period:

2020 - 2024

Location:

Neurodegenerative diseases are a pressing concern in Europe and Alzheimer's disease costs was estimated to 100-200 billion euros in the European union in 2010 alone. To address the looming Alzheimer's disease crisis medical researchers are asking fundamental questions about metabolic waste clearance in the brain. In particular, the theories suggest that brain clearance is most efficient during sleep. New theories have upended centuries of previous medical opinion; however these theories are not without controversy and the experimental methods themselves have been called into question. Mathematical modeling have revealed deficiencies and revised the new theories; but these mathematical models fall short due to a lack of accounting for complex geometries, neglecting coupling effects, multi-physics, or relevant time scales. As such, advancing the mathematical modeling of the medical theories is a timely subject and is getting increased attention. This proposal aim to provide the next generation of mathematical models and software tools for this important medical problem. In particular, we address appropriate mathematical models that encompass not only multi-physics effects at both short and long time-scales but also involve fundamental questions of the appropriate preconditioning of monolithic multi-scale solvers. In our solution algorithms we employ a newly developed multi-level component where Laplace operators of mixed fractionality are utilised at the interface. This utility has not been explored for multi-physics problems despite their canonical appearance. This year we have together with researchers at the Rikshospital (Per Kristian Eide and Geir Ringstad) published on the effect of sleep with regards the brain clearance in the journal Brain. The study showed that there were significant differences and received significant attention internationally. Further, we have advanced our modeling substantially, resulting in a book to be published at Springer and several matematical papers in good mathematical journals such as SIAM.

Neurodegenerative diseases are a pressing concern in Europe and Alzheimer's disease costs was estimated to 100-200 billion euros in the European union in 2010 alone. To address the looming Alzheimer's disease crisis medical researchers are asking fundamental questions about metabolic waste clearance in the brain. New theories have upended centuries of previous medical opinion; however these theories are not without controversy and the experimental methods themselves have been called into question. Mathematical modeling (some by the PI) have revealed deficiencies and revised the new theories; but these mathematical models fall short due to a lack of accounting for complex geometries, neglecting coupling effects, multi-physics, or relevant time scales. As such, advancing the mathematical modeling of the medical theories is a timely subject and is getting increased attention. This proposal aim to provide the next generation of mathematical models and software tools for this important medical problem. In particular, we address appropriate mathematical models that encompass not only multi-physics effects at both short and long time-scales but also involve fundamental questions of the appropriate preconditioning of monolithic multi-scale solvers. In our solution algorithms we employ a newly developed multi-level component where Laplace operators of mixed fractionality are utilised at the interface. This utility has not been explored for multi-physics problems despite their canonical appearance. The mathematical toolchain and corresponding physiological simulations will be developed together with selected leading experts in biomedical mathematical modeling of the brain, biomedical scientific computing, and magnetic resonance imaging (MRI) brain-water imaging in developing our methodologies. As such, we aim to continue our tradition of publications in top-tier journals (PNAS, JCI etc.).

Publications from Cristin

No publications found

No publications found

No publications found

Activity:

FRINATEK-Fri prosj.st. mat.,naturv.,tek