MEMENTO-VAScular COmponents of Dementia

Alzheimer's disease (AD) is a neurodegenerative disorder thought to be caused by the accumulation of the peptide amyloid beta and the hyperphosphorylated tau protein in the brain. There are increasing arguments in favor of an important role of vascular damages in the development and progression of AD.

The time course of these vascular alterations and how they relate to dementia and AD pathology remain unclear, as no protocol that allows the development of the diverse vascular pathology to be scored, and hence to be tracked with ageing, has so far been developed and widely validated. The aims of this project are to investigate, in a large clinical sample of patients presenting either isolated cognitive complaints or light to mild cognitive deficits, how vascular risk factors and vascular alterations (assessed at macro and micro levels) relate to cerebrovascular disease and cognitive decline.

The primary objective of this ancillary study is to investigate the prospective association between vascular risk factors, inflammation markers and vascular damages on cognitive decline and neurodegeneration progression over up to 4 years of follow-up in a sample of individuals presenting with a spectrum of cognitive profiles ranging from isolated cognitive complaints to cognitive deficits without dementia.

The secondary objectives are the following

• To investigate the role of vascular risk factors (diabetes, hypertension, hypercholesterolemia) and vascular damages on progression to clinical dementia over up to 4-year follow-up.
• To study whether the interaction between changes in markers of macrovascular and microvascular structures on cognitive deficits progression.
• To study the association between in BP, hypertension, antihypertensive treatments and vascular damages, progression of cerebrovascular disease seen at MRI and cognitive decline and dementia risk
• To assess the temporality of vascular damages burden on neurodegeneration
• To assess the association between retinal vasculature defect and brain neurovascular damages
• To study the link between vascular damages and AD pathology (Cerebro-Spinal Fluid (CSF) and Positron emission tomography (TEP) amyloid imaging) biomarkers in the subsample of participants having all measures available
• To investigate how inflammatory markers mediate the association between vascular damages and neurodegeneration
• To assess whether vascular factors and neurodegenerative factors act independently or synergistically on the course of cognitive decline
• To assess simultaneously the impact of vascular damages on end organs (brain, eye, and kidney)
• To study the correlation between cerebral blood flow, measured by Arterial spin-Labeled (ASL) MRI and cognitive decline
• To study whether genetic polymorphisms revealed from genome-wide association studies (GWAS) of AD of vascular factors could modulate the association between vascular damages and cognitive decline