MEMENTO-VAScular COmponents of Dementia (VASCOD)

A Multicenter national longitudinal cohort study including at least 800 individuals recruited from French Research Memory Centers and followed up over 36 months and included in Memento.

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

Pulse wave velocity assessment Cerebral MRI including Arterial Spin Labeling (ASL) and Magnetic Resonance Angiography (MRA) sequences Ophthalmological exams: Spectral Domain-Optical Coherence Tomography (SD-OCT), colour photographs of the retina, visual acuity and axial lenght measurement Neuropsychological testing and behaviorial and mood scales Urinary albumin excretion measurement

standardized criteria : Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and National Institute of Neurological and Communicative Disorders and Stroke Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) classifications

Inclusion Criteria: Participants to MEMENTO-Vascod should be included in MEMENTO. To have signed a specific MEMENTO-Vascod informed consent form, prior to any Vascod ancillary study related procedures To be aged 50 years old and above To have a Clinical Dementia Rating scale <0.5 and to be not demented; Exclusion Criteria: Are under guardianship Live in skilled nursing facility Are Pregnant or breast feeding women Meet brain MRI exclusion criteria (Same criteria as in Memento main protocol)