Vascular Alteration and Evolution of Cognitive Impairment

Study Overview
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Brief Summary
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In the cross sectional study Adelahyde 1 which took place between 2001 and 2005, the investigators data suggest that vascular alterations may play a role in the setting of subjective memory complaints. This longitudinal study (Adelahyde 2) aims to confirm the role of vascular factors in the evolution of cognitive function and dementia.

Detailed Description
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Background: The role of arterial hypertension and vascular alterations in the development of cognitive decline is a major issue in both research and clinical practice. In a recently published cross-sectional study (Kearney-Schwartz, Rossignol et al. 2009), conducted on the ADELAHYDE cohort comprised of older hypertensive patients with memory complaints, the investigators showed the association of arterial changes (hypertrophy and arterial stiffness, endothelial dysfunction) with cognitive functions and/or white matter hyperintensities on MRI. A longitudinal study is the only means to confirm the role of vascular factors in the evolution of cognitive function and onset of dementia. Objectives: i) Primary: To establish, in the ADELAHYDE cohort, the relationship between vascular alterations assessed at baseline during the cross-sectional study (hypertrophy and arterial stiffness, endothelial dysfunction) and the evolution of cognitive function (primary study endpoint) over a 8-year follow-up period; ii) Secondary a) To investigate the evolution of white matter hyperintensities on MRI (secondary study endpoint) as a function of peripheral vascular status, and especially of endothelial function. b) Determine the role of genetic factors and biomarkers of oxidative stress (from DNA and serum biobanks collected at the first visit) in the evolution of cognitive functions and white matter hyperintensities. Methods: Prospective longitudinal single center study. All patients (378 subjects) who participated in the baseline cross-sectional study conducted between 2001 and 2005, will be reconvened at the Clinical Investigation Centre (CIC) of Nancy. As in the cross-sectional study, the following will be assessed in this longitudinal phase: pulse wave velocity (PWV), carotid ultrasonography, flow-mediated dilation, brain MRI with semi-quantification of white matter hyperintensities, cognitive function evaluation and measurement of various biomarkers of endothelial function. Expected fallouts: A major benefit of this project is that this cohort has already been explored in terms of cognitive function, arterial properties and neurovascular imaging (MRI). Thus, the programmed reconvening of these subjects for this project in 2011 will enable us to identify the role of vascular alterations in the evolution of cognitive function and leucoaraiosis in this population at high risk of dementia over a period of at least 8 years. Finally, it could pave the way for further investigations, notably in the field of cognitive impairment prevention, aimed at reducing or delaying the onset of dementia by acting on the vascular factor, which is potentially modifiable.

Official Title
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Arterial Function and Structure and Evolution of Cognitive Impairment in Elderly Hypertensive Subjects With Subjective Memory Complaints

Conditions
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Cognitive Impairment

Intervention / Treatment
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* Biological: blood sampling
* Procedure: brain MRI and TEP cerebral
* Other: Assessment of cognitive functions
* Other: Electrocardiogram and blood pressure
* Procedure: Vascular explorations
* Biological: Urine sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient who have participated Adelahyde 1 study patient who have signed a consent patient who have a social security Exclusion Criteria: patient who can't understand information letter and who is not under legal protection

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Elderly hypertensive patients with mnemonic subjective<br>Elderly hypertensive patients with mnemonic subjective without dementia. Interventions : blood sampling brain MRI Assessment of cognitive functions brain MRI and TEP cerebral Electrocardiogram and blood pressure Pulse wave velocity Quality of life questionnaire Urine sample Vascular explorations | Biological: blood sampling<br>* take a sample of blood, 46 ml<br>Procedure: brain MRI and TEP cerebral<br>* magnetic resonance imaging<br>Other: Assessment of cognitive functions<br>* Folstein MMSE, Mac Nair scale, Depression (GDS) scale, The Benton Visual Retention Test, Test of verbal fluency, formal and categorical, Trail Making Test, Grober et Buschke scale (RL/RI-16), Apathy Robert scale, Praxis rating Scale .<br>Other: Electrocardiogram and blood pressure<br>* Electrocardiogramm Blood pressure monitoring<br>Procedure: Vascular explorations<br>* Pulse wave velocity, VWF, IMT<br>Biological: Urine sample<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global memory, visual retention and verbal fluency composite score |  | up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vascular exploration | Pulse wave velocity, VWF, IMT | up to two years | 
| white matter hyperintensities by fazekas score. | Hyperintensities of white matter will be classified following the Fazekas scale (6 ranks. | up to two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Cognitive function