The purpose of the study is to test the hypothesis of slowing the progression of White Matter Lesions (WML) by lowering blood pressure (BP) in patients with cognitive complaints and a moderate to high grade of WML on brain MRI.

SCIENTIFIC BACKGROUND: White Matter Lesions (WML) are cerebrovascular abnormalities discovered on MRI that are associated with an increased risk of dementia. High blood pressure (BP) is a major risk factor for WML. WML are therefore key lesions in the causal chain linking vascular factors and dementia, particularly Alzheimer's disease.

However, it has not been shown that lowering BP could limit the progression of the WML in people with cognitive impairment.

OBJECTIVES: To test the hypothesis of slowing progression of WML by lowering BP in patients with memory complaints with a moderate to high grade of WML on brain MRI.

STUDY DESIGN: PROBE (Prospective randomized open blinded end-point) trial. Blind reading of both MRI for every patient in each group. After stratified randomization on age, sex and center, patients will be assigned to two strategies:

• Reinforced Group (RG): enhanced strategy aiming at a systolic BP <135 mmHg;
• Usual Group (UG): usual strategy based on the usual routine care.

SAMPLE SIZE: patients will be enrolled (410 in each arm) in 12 Memory Resources and Research Center (CMRR) with access to 1.5 T or more MRI.

CONDUCT OF THE STUDY:

Duration of the inclusion period: 96 months and 2 weeks. Patient participation duration: 36 months + 6 months max Total study duration: 11 years. Clinical and para-clinical evaluation: MRI as part of research at the beginning of the study and before the end of the study at 36 months + 6 months max (primary endpoint); Clinical evaluation of neuropsychological tests at the beginning of the study and yearly ; walking speed measurement single leg stance balance test ; repeated BP measurements; monitoring of neurological signs and symptoms; blood test at the beginning of the study (electrolytes, lipid profiles, fasting blood glucose, if not existing); MRI if not existing for validation of the inclusion criterion and performed in the ordinary course.

Inclusion Criteria:

• 60 to 88 years old patients;
• Patient with cognitive complaint with MMSE ≥ 20performed within 6 months prior to enrollment (with or without dementia)
• Patient with a socio-educational level ≥ 3
• Presence of hyperintensities of moderate to high grade on the last MRI or old scan (grades C and D on the modified Scheltens scale, grades 2/3 Fazekas).
• Hypertension defined by a Systolic Blood Pressure (SBP) and / or a Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg, treated or not
• Affiliation to a social security system
• Informed consent given, signed consent

Exclusion Criteria:

• Presence of severe orthostatic hypotension defined as a decrease of 30 mmHg in SBP standing within 3 minutes
• Contraindication to MRI (presence of ferromagnetic foreign body (especially some intracranial clips, some heart valves, intraocular foreign bodies, metal prosthesis), subject carrying pacemaker, claustrophobic participants)
• Severe diseases associated with a life expectancy of less than 3 months;
• Major physical impairments that can interfere with the feasibility of the tests (sight, hearing ...)
• Presence of another dementia different than Alzheimer's disease vascular dementia or mixed dementia,
• Persons under guardianship;
• Secondary hypertension: renovascular hypertension, primary aldosteronism, pheochromocytoma ...;
• Patient already receiving 4 or more antihypertensive drugs at maximum dosage
• Patient participating in another clinical research study on drug requiring exclusion period
• severe renal impairment