Vascular and amyloid pathology in neurodegeneration and cognition: A population imaging study

Dementia is a clinical syndrome in which the brain gradually deteriorates, causing loved ones to slowly be lost, even though they are still there. As the population gets older, the number of people with dementia increases. However, much is still unknown about the causes of dementia and current treatments hardly improve symptoms. The two main causes of dementia are damage to the blood vessels and the buildup of the amyloid-beta protein. These processes can occur separately, but can also influence each other. This dissertation investigates these causes and their interaction in a group of people without dementia. It also explores how a new blood biomarker might give us more insight into the disease.

Chapter 2 shows that a higher level of education might protect against the development of brain damage. We also see that people with a higher risk of heart and blood vessel diseases tend to have more amyloid-beta buildup in their brains. Chapter 3 reveals that higher levels of a blood biomarker called plasma NfL are linked to worse thinking abilities and mainly more damage to the brain's white matter. Additionally, the connection between amyloid-beta and thinking abilities is stronger in people with more calcification in their blood vessels.

This thesis shows indications of an interaction between vascular problems and amyloid-beta, both in their origin and in their impact on thinking abilities in people without dementia. The final chapter places these findings in a broader context and highlights where further research is needed to better understand this interaction.