Evaluation of the Link Between Carotid Arterial Wall Viscosity and Major Neurocognitive Disorders

Официальное название

Evaluation of the Link Between Carotid Arterial Wall Viscosity and Major Neurocognitive Disorders of Vascular Origin or Linked to Alzheimer's Disease

Обзор

The mechanical behavior of conductance arteries is viscoelastic. While the elastic component has been extensively studied, the viscous component has often been neglected for methodological reasons and also because it was considered weak. Unlike a purely elastic solid, which exhibits instantaneous deformation/relaxation upon application/discontinuation of a force, a viscoelastic solid is characterized, from a mechanical point of view, by a delay between the application or discontinuation of the force and deformation. Thus, at the arterial level, the elasticity of the arterial wall allows the internal diameter to increase proportionally to the blood pressure during systole. The viscous component will induce a delay in diameter restoration, resulting in a larger diameter at each pressure level during the diastolic phase compared to the systolic phase. This results in a shift between the systolic and diastolic curves of the pressure-diameter relationship, creating a hysteresis loop. From a thermodynamic point of view, while a purely elastic material fully restores the energy stored during the loading phase, viscoelastic arteries will incompletely restore this energy. Thus, the surface of the hysteresis loop reflects the energy dissipated during each cardiac cycle (WV), and the area under the loading phase curve represents the energy stored by the arterial wall (WE) during the latter. Thus, arterial wall viscosity (APV) can be expressed either as the absolute value of WV or as a function of the stored energy (WV/WE). Physiologically, this energy loss is low. Its increase could be accompanied by excessive energy dissipation, leading to increased cardiac work and cardio-circulatory decoupling. Conversely, low parietal viscosity could lead to damage to peripheral organs by excessive transmission of pulsatile energy to the periphery due to lack of damping.

Подробное описание

Preliminary work in the laboratories has highlighted the role of vaso-relaxing endothelial factors and smooth muscle tone in the regulation of the Arterial Pulse Rate (APR) of the radial artery in the basal and stimulated state and the alteration of this stimulated regulation during Arterial Hypertension (AH). Furthermore, a decrease in relative carotid APR in middle-aged subjects compared to young subjects, and an increase in carotid APR in diabetic patients has been found in unpublished results. The link between aortic arterial stiffness and the existence of vascular dementia but also Alzheimer's is strongly suggested. Indeed, the increase in arterial stiffness could be responsible for an increase in pulsatility transmitted to the brain, participating in the accumulation of beta amyloid proteins. A probable inflammatory and oxidative stress component could also have an added deleterious role through the production of free radicals. Thus, previous studies have shown the existence of a link between arterial stiffness and the presence of leukoaraiosis, lacunae, microbleeds but also with brain volume and the progression of cerebral atrophy. These repercussions on the cerebral parenchyma are visible on MRI.

A link has also been suggested between increased arterial stiffness and impaired cognitive function (as demonstrated by neurocognitive tests) or the presence of markers of small vessel damage in neuroimaging (microbleeds, lacunae, leukoaraiosis). One hypothesis to explain this link is that arterial stiffness promotes impaired hippocampal microcirculation. Other studies have shown that carotid-femoral pressure wave velocity (CFV), a marker of large arterial stiffness, was higher in populations with Alzheimer's disease and vascular dementia than in older populations without cognitive impairment or with minor neurocognitive impairment.

However, no studies have evaluated the link between baseline VPA and vascular dementia or Alzheimer's disease.

Our study suggests that carotid VPA is associated with increased cerebrovascular injury, impaired cognitive testing, and the diagnosis of vascular dementia.

Вмешательства

• Диагностический тест Assessment of carotid wall viscosity in patients with vascular dementia
  Carotid wall viscosity will be assessed by simultaneous and continuous measurement by 2 operators of local pressure and diameter at the level of the right and left carotids by coupling echotracking (Vevo 3100®) with applanation tonometry (Millar®). 3 successive measurements will be carried out. These measurements will establish the diameter-pressure relationship and its analysis will allow the calculation of wall viscosity by measuring the area under the curve of this relationship during the car
• Диагностический тест Assessment of carotid wall viscosity in patients with Alzheimer's disease
  Carotid wall viscosity will be assessed by simultaneous and continuous measurement by 2 operators of local pressure and diameter at the level of the right and left carotids by coupling echotracking (Vevo 3100®) with applanation tonometry (Millar®). 3 successive measurements will be carried out. These measurements will establish the diameter-pressure relationship and its analysis will allow the calculation of wall viscosity by measuring the area under the curve of this relationship during the car
• Диагностический тест Assessment of carotid wall viscosity in patients not presenting dementia.
  Carotid wall viscosity will be assessed by simultaneous and continuous measurement by 2 operators of local pressure and diameter at the level of the right and left carotids by coupling echotracking (Vevo 3100®) with applanation tonometry (Millar®). 3 successive measurements will be carried out. These measurements will establish the diameter-pressure relationship and its analysis will allow the calculation of wall viscosity by measuring the area under the curve of this relationship during the car

Первичные конечные точки

• Evaluation of the difference in relative arterial wall viscosity value of the common carotid artery of patients with vascular dementia compared to that of patients with Alzheimer's disease [Срок оценки: Day 1]
• Evaluation of the difference in relative arterial wall viscosity value of the common carotid artery of patients with vascular dementia compared to that of patients not presenting dementia [Срок оценки: enrollment visit]

Вторичные конечные точки (9)

• Evaluation of the link between arterial parietal viscosity of the common carotid artery and the intensity of cerebral vascular [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (MMSE) [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (Gröber test) [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (verbal fluency) [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (cognitive performance score (BREF)) [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (score oral naming score (DO80)) [Срок оценки: enrollment visit]
• Study of the link between arterial parietal viscosity of the common carotid artery and the severity of cognitive impairment (number of successful gestural praxis) [Срок оценки: enrollment visit]
• link between arterial stiffness (carotid and aortic) and the intensity of cerebral vascular lesions in MRI [Срок оценки: Enrollment visit]
• Link between arterial stiffness (carotid and aortic) and the intensity of cerebral vascular lesions in MRI as well as with the severity of cognitive impairment [Срок оценки: enrollment visit]

Критерии участия

Критерии включения

• Age over 70
• Memory consultation consultant (neurology or geriatrics)
• Brain MRI less than one year old or planned as part of the cognitive assessment performed.
• Patient diagnosed with Alzheimer's disease according to DSM-5 criteria or vascular dementia according to DSM-5 criteria, or presenting a memory complaint without evidence of a dementia-related condition.
• No objection from the patient or their caregiver.
• Patient covered by a health insurance plan

Критерии исключения

• Known unilateral or bilateral carotid stenosis or history of carotid surgery
• Permanent CA/AF
• Patient presenting with confusion
• Known psychiatric illness (severe depression, psychosis, etc.)
• Non-vascular, non-Alzheimer's dementia (e.g., Lewy Body Dementia, Parkinsonian Dementia, Progressive Supranuclear Palsy)
• Refusal to participate
• MMS less than or equal to 10
• Contraindication to performing an MRI
• Any acute decompensated pathology
• Patient under guardianship or curatorship

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

Франция · 1 центр

• University Rouen Hospital — Rouen

Идентификаторы

NCT: NCT07205003 · 2021/021/OB · 2021-A00291-40

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗