Retina Microvascular Remodeling and Cognitive Function In Hypertension

Overview

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).

Full Title of Study: “Retina Microvascular Remodeling and Cognitive Function In Hypertension : Eyebrain”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: September 2017

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.

Interventions

  • Behavioral: Cognitive tests
    • 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)
  • Biological: Blood test
    • 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
  • Radiation: Brain and aorta RMI
    • 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.
  • Other: Adaptative optics
    • 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.

Arms, Groups and Cohorts

  • Hypertension and progressive MCI
    • 50 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics.
  • Hypertension and stable MCI
    • 50 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics.
  • Hypertension, without MCI
    • 60 subjects will perform brain and aorta RMI, blood test, cognitive tests and adaptative optics.

Clinical Trial Outcome Measures

Primary Measures

  • Relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients.
    • Time Frame: September 2017

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 65 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Institute of Cardiometabolism and Nutrition, France
  • Collaborator
    • Fondation de Recherche sur l’Hypertension Artérielle
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • David Rosenbaum, Dr, 01 42 17 57 74, david.rosenbaum@psl.aphp.fr

References

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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.

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.

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.

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.

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.

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.

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.

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.

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