Clinical trial NCT02264899: MEMENTO-VAScular COmponents of Dementia
Official title: MEMENTO-VAScular COmponents of Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease (AD)
Alzheimer's Disease (AD) Related Disorders
Keywords: Alzheimer's disease
Mild Cognitive Impairment
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry for Health and Solidarity, France
First posted: 2014-10-15
Enrollment: 332
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Change in cognitive performances over
timeFrame: 36 months from baseline
Secondary outcomes:
measure: Progression to clinical dementia of Alzheimer's type according to standardized criteria
timeFrame: 36 months from baseline
measure: Change in CSF and blood amyloid biomarkers of AD
timeFrame: 24 months from baseline
measure: Change in brain atrophy and hippocampal volumes
timeFrame: 24 months from baseline
measure: Progression of small vessels disease markers (white matter lesions, lacunar infarcts, microbleeds)
timeFrame: 24 months from baseline
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Bordeaux
country: France
facility: CHU de Bordeaux - Pellegrin
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: CHU de Lille
city: Lyon
country: France
facility: Hospices civils de Lyon
city: Marseille
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU de Montpellier
city: Paris
country: France
facility: AP-HP - Hôpital BROCA
city: Paris
country: France
facility: AP-HP - Hôpital LARIBOISIERE
city: Strasbourg
country: France
facility: CHU de Strasbourg
Study officials:
affiliation: CIC-EC1401 - ISPED - CHU de Bodeaux
name: Genevieve CHENE, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: CIC-EC1401 - ISPED - CHU de Bordeaux
name: Geneviève CHENE, Prof
role: STUDY_CHAIR
affiliation: CIC-EC1401 - ISPED - CHU de Bordeaux
name: Carole DUFOUIL, Director
role: STUDY_DIRECTOR
References: