Retina Microvascular Remodeling and Cognitive Function In Hypertension

Study Overview
=================
Brief Summary
-----------------
This study aims to determine the relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients. The study plans to enrol 160 patients (100 patients with mild cognitive impairment -MCI- and 60 without MCI).

Detailed Description
-----------------
Our project stands on physiopathological and cognitive angles, and is mainly based on the major role of large and small arteries elasticity on cognitive aging. It will benefit from the recent innovative accurate and non invasive techniques such as MRI for central large arteries and adaptative optics for retina arterioles imaging. Study population is the following: 60 patients with hypertension and no MCI, 50 patients with hypertension and stable MCI, without dementia 50 patients with hypertension and progressive MCI, without dementia Every patients will perform a medical interview and examination, an MRI (brain + aorta), adaptative optics imaging, a cognitive tests and a blood test. Primary outcome is to determine the relationships between retina micro-vascular remodeling and cognitive function in this population.

Official Title
-----------------
Retina Microvascular Remodeling and Cognitive Function In Hypertension : Eyebrain

Conditions
-----------------
Hypertension, Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Behavioral: Cognitive tests
* Biological: Blood test
* Radiation: Brain and aorta RMI
* Other: Adaptative optics


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 65 or more hypertension (BP ≥140/90 mmHg and/or antihypertensive treatment) Signed informed consent by the patient Sufficient mastery of the French language to perform neuropsychological tests Exclusion Criteria: Impossibility to visualize the retinal : severe cataract Dementia (defined by MMSE<20) Clinical stroke Severe or resistant Hypertension Hypertension treated with more than 3 different pharmacological classes any other disease that may interfere with the assessment of cognitive disorders (epilepsy, Parkinson's disease, major depression, schizophrenia, manic-depressive) Enrolment in a therapeutic trial that could interfere with the main objective Less than 4 years of formal education Illiterate, unable to read, write or count major physical problems that may interfere with the tests (sight, hearing, ...) Short term life threatening disease Non-affiliation to a healthcare system Consent refusal Contraindication to MRI including claustrophobia, metallic devices, pacemaker, mechanical valve implanted before 1985, and nursing, as well as technical contra-indication: patient diameter > 70 cm or/and weight > 250 kg

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertension and progressive MCI<br>50 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics. | Behavioral: Cognitive tests<br>* Cognitive tests include: The MMSE (Mini Mental State Examination) Free and Cued Selective Recall Reminding Test (FCSRT). Executive functions (fluencies, TMT A and B, span). Tests of verbal fluency (literal and category) Digit symbol substitution test or Wechsler adult intelligence scale (W.A.I.S) The Clinical Dementia Rating Scale The IADL scale evaluates autonomy. Geriatric Depression screening Scale (GDS)<br>Biological: Blood test<br>* A blood test will be performed in order to collect following parameters: Urea, BUN, Creatinine, Potassium, Sodium, hematocrit, hsCRP, NFS, Pq, LDL-C, HDL-C, Triglycerides, Lp(a), Lp-PLA2 as well as fasting glucose, HbA1C and microalbuminuria<br>Radiation: Brain and aorta RMI<br>* A magnetic resonance imaging exam will be performed at the Neuroimaging Research Center of the Pitié-Salpêtrière Hospital. This exam will be optimized to fit in 30 minutes. Indeed brain 3D T1 and T2 FLAIR imaging lasts 15 minutes while cine and velocity encoded imaging of the aorta lasts 15 minutes.<br>Other: Adaptative optics<br>* The retina adaptative optic imaging will be performed at the Unité de prevention des maladies cardiovasculaires Pitié Salpetrière Hospital. This exam lasts 10 minutes including patient positioning and imaging.<br>|
| Hypertension and stable MCI<br>50 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics. | Behavioral: Cognitive tests<br>* Cognitive tests include: The MMSE (Mini Mental State Examination) Free and Cued Selective Recall Reminding Test (FCSRT). Executive functions (fluencies, TMT A and B, span). Tests of verbal fluency (literal and category) Digit symbol substitution test or Wechsler adult intelligence scale (W.A.I.S) The Clinical Dementia Rating Scale The IADL scale evaluates autonomy. Geriatric Depression screening Scale (GDS)<br>Biological: Blood test<br>* A blood test will be performed in order to collect following parameters: Urea, BUN, Creatinine, Potassium, Sodium, hematocrit, hsCRP, NFS, Pq, LDL-C, HDL-C, Triglycerides, Lp(a), Lp-PLA2 as well as fasting glucose, HbA1C and microalbuminuria<br>Radiation: Brain and aorta RMI<br>* A magnetic resonance imaging exam will be performed at the Neuroimaging Research Center of the Pitié-Salpêtrière Hospital. This exam will be optimized to fit in 30 minutes. Indeed brain 3D T1 and T2 FLAIR imaging lasts 15 minutes while cine and velocity encoded imaging of the aorta lasts 15 minutes.<br>Other: Adaptative optics<br>* The retina adaptative optic imaging will be performed at the Unité de prevention des maladies cardiovasculaires Pitié Salpetrière Hospital. This exam lasts 10 minutes including patient positioning and imaging.<br>|
| Hypertension, without MCI<br>60 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics. | Behavioral: Cognitive tests<br>* Cognitive tests include: The MMSE (Mini Mental State Examination) Free and Cued Selective Recall Reminding Test (FCSRT). Executive functions (fluencies, TMT A and B, span). Tests of verbal fluency (literal and category) Digit symbol substitution test or Wechsler adult intelligence scale (W.A.I.S) The Clinical Dementia Rating Scale The IADL scale evaluates autonomy. Geriatric Depression screening Scale (GDS)<br>Biological: Blood test<br>* A blood test will be performed in order to collect following parameters: Urea, BUN, Creatinine, Potassium, Sodium, hematocrit, hsCRP, NFS, Pq, LDL-C, HDL-C, Triglycerides, Lp(a), Lp-PLA2 as well as fasting glucose, HbA1C and microalbuminuria<br>Radiation: Brain and aorta RMI<br>* A magnetic resonance imaging exam will be performed at the Neuroimaging Research Center of the Pitié-Salpêtrière Hospital. This exam will be optimized to fit in 30 minutes. Indeed brain 3D T1 and T2 FLAIR imaging lasts 15 minutes while cine and velocity encoded imaging of the aorta lasts 15 minutes.<br>Other: Adaptative optics<br>* The retina adaptative optic imaging will be performed at the Unité de prevention des maladies cardiovasculaires Pitié Salpetrière Hospital. This exam lasts 10 minutes including patient positioning and imaging.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients. |  | September 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Associations between cognitive function and proximal aortic stiffness indices estimated from MRI images. |  | September 2017 | 
| • Associations between retina arteriolar remodelling and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images. |  | September 2017 | 
| • Associations between retina arteriolar remodelling and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images. |  | September 2017 | 
| • Associations between proximal aortic stiffness and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images. |  | September 2017 | 
| • Associations between proximal aortic stiffness and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images. |  | September 2017 | 
| • Associations between retina arteriolar remodelling and proximal aortic stiffness indices. |  | September 2017 |