Around 55 million people are affected by dementia worldwide. Prevention appears to be essential in the absence of curative treatment. Among critical pathways involved in dementia, neuroinflammation appears to play an important role. However, the underlying mechanisms by which neuroinflammation may damage the brain and its primary determinants remain partly elucidated. Unhealthy lifestyles, including diet, could increase the level of neuroinflammation and subsequently accelerate cognitive aging trajectories.
We will look into the composition of lifestyle-related patterns most likely to foster (or alternatively decrease) neuroinflammation on the path to dementia, which have yet been undetermined. Our general objective is to identify lifestyle-related factor profiles associated with levels of neuroinflammation and with dementia outcomes (cognitive decline, cerebral structural alterations at MRI and dementia risk).
We will consider modifiable risk factors from the Lancet Commission for dementia prevention as well as dietary surveys to build: Life’s Essential 8; Lifestyle for BRAin health score; and a diet inflammatory index. Studied outcomes include (1) repeated measures of blood GFAP to assess trajectories of neuroinflammation, and (2) repeated measures of cognition, MRI phenotypes and incident dementia. We will also consider (3) genetic risk factors for dementia as potential modifiers (Apoe4 genotype and a polygenic risk score of Alzheimer’s disease). We plan to test associations of risk factor scores with trajectories of plasma GFAP and cognition as well as incident dementia, all adjusted on confusion factors, and to subsequently explore mediation analyses (lifestyle > neuroinflammation > cognitive outcomes).
This project will allow (1) to identify the most effective prevention targets capable of modulating neuroinflammation in early brain aging stages, and (2) to identify a high-risk population in need of personalized and adapted prevention strategies.
