Fighting cognitive decline and dementia caused by small vessel disease

Stopping Cognitive Decline and Dementia by Fighting Covert Cerebral Small Vessel Disease

This study is trying to see how changes in the brain and eye blood vessels can help predict dementia risk in people over 60 with small vessel disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 60 Years to 88 Years
• Sex: All
• Sponsor: University Hospital, Bordeaux (Academic / other)
• Locations: 2 sites (Bordeaux and 1 other locations)
• Trial ID: NCT05306834 on ClinicalTrials.gov

What this trial studies

This study investigates the relationship between brain and retinal microvasculature imaging characteristics and molecular biomarkers in patients aged 60 and older with varying degrees of covert cerebral small vessel disease (cSVD). It aims to develop innovative diagnostic and risk prediction tools for cSVD and its associated cognitive decline and dementia. By comparing two groups of patients—those with minimal and those with extensive cSVD—the study seeks to better understand the predictive ability of cSVD for dementia risk and improve management strategies. The interventions include retinal imaging, blood samples, cardiovascular risk evaluations, brain imaging (MRI), and cognitive tests.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 60 to 88 years with varying degrees of cognitive impairment and brain MRI results indicating either minimal or extensive cSVD.

Not a fit: Patients outside the age range of 60 to 88 years or those without cognitive complaints or MRI evidence of cSVD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved diagnostic tools and management strategies for preventing cognitive decline and dementia in older adults.

How similar studies have performed: While there is limited evidence on specific mechanistic treatments for cSVD, the study's approach of using multimodal biomarkers is innovative and may provide new insights into managing cognitive decline.

Eligibility criteria

Inclusion Criteria:

For the extensive cSVD patient group

1. For the extensive cSVD patient group included in the LEOPOLD trial:

   * Patients aged 60 to 88 years,
   * Patients included in the LEOPOLD trial and having performed their brain MRI on SIEMENS PRISMA machine
   * Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
   * Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study).
2. For the extensive cSVD patient group not included in the LEOPOLD trial:

   * Patients aged 60 to 88 years,
   * Patients with a cognitive complaint MMSE ≥ 20 performed in the 6 months before inclusion, associated or not with impaired cognitive tests and/or diaognosis of incipient dementia without pronounced cognitive deterioration,
   * Patients with a socio-educational level ≥ 3,
   * Patients with a moderate to high grade of hypersignals on an MRI OR on an CT scan performed prior inclusion (grades C and D of the modified Scheltens scale or grade 2/3 Fazekas),
   * Arterial hypertension defined by a Systolic Blood Pressure (SBP) and / or Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg (according to the definition of the national health authority \[HAS\]), treated or not, confirmed within the previous 12 months or at the latest on the day of inclusion.
   * Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
   * Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study)

For the minimal cSVD patient group:

* Patients aged 60 to 88 years,
* Patients with a cognitive complaint (MMSE ≥ 20 performed at the SHIVA inclusion visit or in the 6 monts prior the visit) associated or not with impaired cognitive tests and/or diagnosis of incipient dementia without pronounced cognitive deterioration,
* Patients with little or no white matter hypertensities on brain MRI (grades 0 or 1 on the Fazekas scale); without lacunes or microbleeds,
* Arterial hypertension defined by a Systolic Blood Pressure (SBP) and / or Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg (according to the definition of the national health authority \[HAS\]), treated or not, confirmed within the previous 12 months or at the latest on the day of inclusion. Blood pressure values for this inclusion criterion can be objectified by several self-measurements performed by the patient at home for 3 days in a sitting or lying position (3 measurements on sitting or lying position and 3 measurements in standing position).
* Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study

Exclusion Criteria:

For Extensive cSVD patient group :

1. For the extensive cSVD patient group also included in the LEOPOLD trial:

   * patients with severe myopia greater than -6 dioptres
   * partients with known allergy to Tropicamide (Mydriaticum®)
   * patients with an extensive cataract
   * patients with ptosis
2. For the extensive cSVD patient group not included in the LEOPOLD trial:

   * Orthostatic hypotension defined by a decrease of 20 mmHg in SBP and / or 10 mmHg in DBP in a standing position at 3 minutes sought in the previous 3 months or on the day of inclusion,
   * Very severe renal impairment (creatinine clearance less than 15 ml / min) on a blood test dating back less than one year,
   * Secondary hypertension: renovascular hypertension, primary hyperaldosteronism, pheochromocytoma...
   * Contraindication to MRI (presence of a ferromagnetic foreign body, in particular certain intracranial clips, certain heart valves, an intraocular foreign body, metal prosthesis, subject carrying a pacemaker, subject carrying prosthetic heart valves incompatible with MRI. ventricular shunt, claustrophobia),
   * Associated severe diseases, with a life expectancy of less than 3 months,
   * Physical problems likely to interfere with the feasibility of the tests (sight, hearing, etc.),
   * Existence of dementia of which the etiology is distinct from Alzheimer's disease, vascular or mixed dementia
   * Persons under tutorship or curatorship,
   * Patients with loss of autonomy living in EHPAD (nursing home)
   * patients with severe myopia greater than -6 dioptres
   * participants with known allergy to Tropicamide (Mydriaticum®)
   * patients with an extensive cataract
   * patients with ptosis

For the minimal cSVD patient group:

* Orthostatic hypotension defined by a decrease of 20 mmHg in SBP and / or 10 mmHg in DBP in a standing position at 3 minutes sought in the previous 3 months or on the day of inclusion,
* Very severe renal impairment (creatinine clearance less than 15 ml / min) on a blood test dating back less than one year,
* Secondary hypertension: renovascular hypertension, primary hyperaldosteronism, pheochromocytoma...
* Contraindication to MRI (presence of a ferromagnetic foreign body, in particular certain intracranial clips, certain heart valves, an intraocular foreign body, metal prosthesis, subject carrying a pacemaker, subject carrying prosthetic heart valves incompatible with MRI. ventricular shunt, claustrophobia),
* Associated severe diseases, with a life expectancy of less than 3 months,
* Physical problems likely to interfere with the feasibility of the tests (sight, hearing, etc.),
* Existence of dementia of which the etiology is distinct from Alzheimer's disease, vascular or mixed dementia
* Persons under tutorship or curatorship,
* Patients with loss of autonomy living in EHPAD (nursing home)
* Patients with severe myopia greater than -6 dioptries
* Patients with known allergy to Tropicamide (Mydriaticum®)
* Patients with an extensive cataract
* Patients with ptosis

Where this trial is running

Bordeaux and 1 other locations

• Bordeaux Hospital — Bordeaux, France (Recruiting)
• Broca Hospital — Paris, France (Recruiting)

Study contacts

• Principal investigator: Olivier HANON, Pr — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Stéphanie DEBETTE, Pr

Conditions Cerebral Small Vessel Diseases; Stroke; Dementia; Cognitive decline; Small vessel disease; Healthy brain aging; Brain imaging; Adaptive optics