Brain health in Atherosclerosis and Cardiovascular risk in mid-life, a PESA-Brain project

Descripción del proyecto

Relacionar la salud cardiaca con el riesgo de Alzheimer

Cada vez hay más pruebas de que las prácticas cardiosaludables también pueden proteger el cerebro. Con el apoyo de las Acciones Marie Skłodowska-Curie, el equipo del proyecto BrainAtCardio pretende investigar cómo las alteraciones cardiovasculares tempranas pueden predisponer a padecer la enfermedad de Alzheimer. Los investigadores examinan los efectos de los síntomas leves de la aterosclerosis y otros factores de riesgo cardiaco sobre la estructura cerebral, el flujo sanguíneo y la memoria en adultos de mediana edad que no presentan ningún síntoma. Mediante imágenes cerebrales de última generación, biomarcadores sanguíneos y pruebas cognitivas, en el proyecto se determinará cómo afecta la salud cardiaca a los primeros signos de neurodegeneración y por qué hombres y mujeres pueden verse afectados de forma diferente.

Objetivo

This project aims to investigate the early associations between cardiovascular health and Alzheimer’s disease (AD) pathology, with a focus on subclinical atherosclerosis (SCAth) and cardiovascular risk factors (CVRFs), in a large cohort of asymptomatic, middle-aged individuals. The overarching objective is to determine how cardiovascular health in subclinical stages influences both cerebrovascular integrity and early AD biomarkers, and to examine how these factors contribute to cognitive decline, with particular emphasis on sex-specific differences.

The proposed research leverages data from the PESA-Brain study, a deeply phenotyped cohort integrating advanced neuroimaging and cognitive testing, with longitudinal cardiovascular and blood-based biomarkers assessments. We will first test the relationships between cardiovascular health markers and cerebrovascular health, focusing on brain perfusion, microstructure, and microinfarcts. We will then explore the links between cardiovascular health and AD pathology, using plasma and brain amyloid and tau biomarkers, as well as cognitive outcomes, including memory and executive function.

The project will employ advanced statistical approaches, such as linear mixed models and mediation analysis, to handle the complexity of multimodal data and examine causal relationships between cardiovascular health, brain pathology, and cognition. By including sex-stratified analyses, the research will provide critical insights into gender-specific susceptibilities, which have been underexplored in previous studies.

The relevance of this project to the work programme lies in its potential to shift the focus of AD prevention to midlife, offering novel insights into the neurobiological pathways that link cardiovascular dysfunction and neurodegeneration. These findings could pave the way for earlier interventions targeting modifiable CVRFs, significantly reducing the incidence and societal burden of dementia in aging populations.