Clinical trial NCT02701855: Retina Microvascular Remodeling and Cognitive Function In Hypertension
Official title: Retina Microvascular Remodeling and Cognitive Function In Hypertension : Eyebrain
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypertension
Mild Cognitive Impairment
Lead sponsor: Institute of Cardiometabolism and Nutrition, France
Sponsor class: OTHER
Collaborators: name: Fondation de Recherche sur l'Hypertension Artérielle
First posted: 2016-03-08
Enrollment: 160
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients' recruitment will be carried out in two centers to ensure inclusion of both patients: 1) with hypertension and without cognitive impairment, 2) with hypertension and with mild cognitive impairment (without dementia) including patients with stable MCI and converters.

Population size: 160 patients:

* 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

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.

Eligibility criteria: Inclusion Criteria:

1. Aged 65 or more
2. hypertension (BP ≥140/90 mmHg and/or antihypertensive treatment)
3. Signed informed consent by the patient
4. Sufficient mastery of the French language to perform neuropsychological tests

Exclusion Criteria:

1. Impossibility to visualize the retinal : severe cataract
2. Dementia (defined by MMSE\<20)
3. Clinical stroke
4. Severe or resistant Hypertension
5. Hypertension treated with more than 3 different pharmacological classes
6. any other disease that may interfere with the assessment of cognitive disorders (epilepsy, Parkinson's disease, major depression, schizophrenia, manic-depressive)
7. Enrolment in a therapeutic trial that could interfere with the main objective
8. Less than 4 years of formal education
9. Illiterate, unable to read, write or count
10. major physical problems that may interfere with the tests (sight, hearing, ...)
11. Short term life threatening disease
12. Non-affiliation to a healthcare system
13. Consent refusal
14. 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

Primary outcomes:
measure: Relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients.
timeFrame: September 2017
Secondary outcomes:
measure: • Associations between cognitive function and proximal aortic stiffness indices estimated from MRI images.
timeFrame: September 2017
measure: • Associations between retina arteriolar remodelling and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images.
timeFrame: September 2017
measure: • Associations between retina arteriolar remodelling and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images.
timeFrame: September 2017
measure: • Associations between proximal aortic stiffness and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images.
timeFrame: September 2017
measure: • Associations between proximal aortic stiffness and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images.
timeFrame: September 2017
measure: • Associations between retina arteriolar remodelling and proximal aortic stiffness indices.
timeFrame: September 2017
Other outcomes:
Locations:
city: Paris
country: France
facility: Unité de prévention des maladies cardiovasculaires Pôle Cardiologie/Métabolisme Hôpital Pitié-Salpétriêre, APHP, 83 bd de l'hôpital,
Study officials:
References:
citation: Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7. doi: 10.1016/S0140-6736(05)67889-0.
citation: Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005 Aug 23;65(4):545-51. doi: 10.1212/01.wnl.0000172914.08967.dc.
citation: Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55. doi: 10.1016/s0197-4580(00)00096-8.
citation: Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005 Aug;4(8):487-99. doi: 10.1016/S1474-4422(05)70141-1.
citation: Perlmutter LS, Barron E, Saperia D, Chui HC. Association between vascular basement membrane components and the lesions of Alzheimer's disease. J Neurosci Res. 1991 Dec;30(4):673-81. doi: 10.1002/jnr.490300411.
citation: Hardy JA, Mann DM, Wester P, Winblad B. An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. Neurobiol Aging. 1986 Nov-Dec;7(6):489-502. doi: 10.1016/0197-4580(86)90086-2.
citation: Vagnucci AH Jr, Li WW. Alzheimer's disease and angiogenesis. Lancet. 2003 Feb 15;361(9357):605-8. doi: 10.1016/S0140-6736(03)12521-4.
citation: Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, Girerd X, Forette F. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke. 2005 Oct;36(10):2193-7. doi: 10.1161/01.STR.0000181771.82518.1c. Epub 2005 Sep 8.
citation: Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension. 2010 Feb;55(2):319-26. doi: 10.1161/HYPERTENSIONAHA.109.141275. Epub 2010 Jan 11.
citation: Redheuil A, Yu WC, Mousseaux E, Harouni AA, Kachenoura N, Wu CO, Bluemke D, Lima JA. Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling. J Am Coll Cardiol. 2011 Sep 13;58(12):1262-70. doi: 10.1016/j.jacc.2011.06.012.
citation: Rosenbaum D, Koch E, Girerd X, Rossant F, Paques M. [Imaging of retinal arteries with adaptative optics, feasibility and reproducibility]. Ann Cardiol Angeiol (Paris). 2013 Jun;62(3):184-8. doi: 10.1016/j.ancard.2013.04.017. Epub 2013 May 29. French.
citation: Herment A, Kachenoura N, Lefort M, Bensalah M, Dogui A, Frouin F, Mousseaux E, De Cesare A. Automated segmentation of the aorta from phase contrast MR images: validation against expert tracing in healthy volunteers and in patients with a dilated aorta. J Magn Reson Imaging. 2010 Apr;31(4):881-8. doi: 10.1002/jmri.22124.
citation: Bollache E, Kachenoura N, Redheuil A, Frouin F, Mousseaux E, Recho P, Lucor D. Descending aorta subject-specific one-dimensional model validated against in vivo data. J Biomech. 2014 Jan 22;47(2):424-31. doi: 10.1016/j.jbiomech.2013.11.009. Epub 2013 Nov 15.
citation: Dogui A, Kachenoura N, Frouin F, Lefort M, De Cesare A, Mousseaux E, Herment A. Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2011 Jan 27;13(1):11. doi: 10.1186/1532-429X-13-11.