The path towards primary prevention of dementia

Dementia is a cognitive state characterised by impairment in multiple cognitive domains, which lead to a reduced ability to perform activities of daily living. Dementia is the leading cause of death in the Netherlands and poses a major societal burden. Dementia has many underlying causes. At high age brain proteopathies such as amyloid aggregation and vascular abnormalities play a major role. Each of these pathologies have their own multifactorial cause including genetic factors and environmental risk factors. There are no therapeutic treatments for dementia-related disorders. Understanding the pathophysiology of dementia and their underlying causes will provide clues to prevention and treatments. So far, studies have addressed specific parts of the pathway towards dementia but an integrative approach that includes multiple pathologies, their risk factors, and genetic factors is currently lacking. Such an approach can only be achieved by pooling datasets and no single study has the power or the data needed to address this challenge. The main objective of this project is to unravel the pathophysiology of dementia in order to find clues for primary prevention by performing a pooled analysis of cohorts on aging and dementia. We will focus on amyloid and vascular pathologies as these are the major causes of dementia. The project has 3 main objectives: Scientific: To investigate the contribution of vascular pathology and amyloid pathology to the development of dementia Public health: To estimate the public health impact of these and other known risk factors in terms of their contribution to the population burden of dementia and the formulation of design guidelines for prevention trials. Infrastructural: To improve data infrastructure and data access to cohorts related to aging and dementia The study will be performed using data from 9 ongoing prospective cohorts studies on cognitive aging or dementia in the Netherlands, which have included over 200.000 participants. The main results will be: - Increased accessibility of cohort data - Publications on the pathophysiology of dementia - Recommendations for primary prevention of dementia