Brain clearance during sleep by cerebrovascular pulsations - a new approach to dementia prevention

Objective

Dementia affects 8 million people in the EU, with cases projected to reach 14 million by 2050 due to an ageing population. It is the final stage of neurodegenerative diseases—Alzheimer’s disease being the most prevalent—marked by a total loss of autonomy with severe cognitive and physical decline. With no cure available, dementia places a growing strain on society underscoring the urgent need for prevention strategies. Recent findings highlight that cerebrovascular pulsations during sleep enhance brain clearance of neurotoxic proteins—key contributors to these diseases. These pulsations are promising targets for prevention as they can be non-invasively measured and modulated through neurostimulation. However, the mechanisms driving this brain clearance process remain unclear, posing a major obstacle to the development of effective strategies. To address this challenge, BrainSomnia will develop advanced multi-scale computational models to study the mechanical aspects of brain clearance. These models will be based on a novel theory of solute transport in deformable porous media, validated through experiments in brain-mimicking hydrogels. By integrating these models with in-vivo data of cerebrovascular dynamics during sleep, BrainSomnia aims to: 1) understand how vascular pulsations drive solute transport; 2) link these pulsations to brain clearance and Alzheimer’s disease progression; 3) identify patterns that optimize brain clearance; and 4) propose a clinical pipeline for dementia risk assessment and therapy. Through its transdisciplinary approach, BrainSomnia introduces a paradigm shift in dementia prevention by including a mechanical pathway alongside standard biochemical approaches. The impacts will improve risk detection and guide revolutionary therapeutic interventions that modulate sleep vascular pulsations to delay or prevent dementia. These efforts aim to preserve patients autonomy, reduce healthcare burdens, and enhance quality of life in an ageing society.