1. Study the BBB permeability in cSVD patients and compare it with healthy control subjects. 2. Examine the relationship between BBB permeability and cognitive function. 3. Examine the relationship between BBB permeability and the extent of…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
BBB permeability, cognitive function, extent of structural lesions on MRI
associated with cSVD (WML, lacunar infarcts, BMB).
Secondary outcome
Sublingual glycocalyx thickness
Background summary
Cerebral small vessel disease (cSVD) is a disorder involving the small brain
arteries. It is associated with structural lesions on brain MRI such as white
matter lesions (WML), lacunar infarcts, brain microbleeds (BMB) and enlarged
Virchow-Robin spaces. Clinically, cSVD is associated with diseases such as
lacunar stroke (LACI) and vascular cognitive impairment (VCI). In addition, the
radiological abnormalities of cSVD appear to be related to disease severity.
Previous studies have shown that the extent of WML on brain MRI are related to
the extent of cognitive decline. Furthermore, progression of WML correlates
with progression of cognitive problems. Recent, preliminary studies have shown
that the blood-brain barrier (BBB) may play a major role in the pathophysiology
of cSVD. The BBB consist of different types of brain cells and endothelial
cells. It forms a protective neuro-vascular unit for the brain by preventing
harmful substances to leak out of the blood vessels into the brain tissue, and
by establishing a stable micro-environment for the neurons. Dysfunction of the
BBB however may lead to disruption of these protective mechanisms, resulting in
aberrant angiogenesis, inflammatory reactions and changed transport of
molecules between blood and brain. It is possible that this disruption plays a
pivotal role in the pathophysiology of cSVD. However, up till now limited data
are available on the role BBB in cSVD.
Furthermore, as cSVD is considered an endotheliopathy and alteration of the
glycocalyx, a layer that covers the vascular endothelium, is associated with an
increased vascular permeability, it is possible that the glycocalyx is
associated with BBB permeability in cSVD. However, the relationship between
glycocalyx and BBB permeabiliteit has never been studied yet.
Study objective
1. Study the BBB permeability in cSVD patients and compare it with healthy
control subjects.
2. Examine the relationship between BBB permeability and cognitive function.
3. Examine the relationship between BBB permeability and the extent of
structural lesions on MRI associated with cSVD (extent of WML, number of
lacunar infarcts and BMB).
4. Examine whether the degree of BBB permeability can predict future cognitive
decline and/or progression of structural lesions on MRI.
5. Examine the relationship between BBB permeability and glycocalyx thickness
in cSVD and healthy control subjects.
Study design
Prospective, observational, follow-up cohort study
Study burden and risks
Participants will receive structural brain MRI at two time points and one
dynamic contrast-enhanced brain MRI (DCE-MRI), the latter requiring
intravascular injection of a contrast agent for which the participant in rare
cases can develop an allergic reaction. It is possible that participants will
experience the MRI scans a uncomfortable due to the small space and the noise.
In addition, participants will receive a neuropsychological assessment (NPA) at
two time points, they will undergo a venipuncture for blood analysis once.
Venipuncture may be experienced as uncomfortable and it may give the
participant a temporary hematoma at the side of venipuncture. A glycocalyx
measurement will be done once. This assessment does not have risks for the
participants.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
LACI patients: A first-ever acute lacunar stroke ;Mild VCI due to cSVD:
- Subjective complaints of cognitive functioning and objective cognitive impairment in at least 1 cognitive domain on cognitive testing, and
- A Clinical Dementia Rating <=1 and a MMSE >=20 (i.e. no dementia), and
- Vascular lesions on brain MRI (lacunar infarts, white matter lesions, deep microbleeds) that suggest a link between the cognitive deficit and cSVD.;Healthy control subjects: Healthy control subjects are included from the general population and matched to the LACI and mild VCI patients according to gender and age.
Exclusion criteria
Exclusion criteria for all subjects:
Cerebrovascular abnormalities in history
o Ischemic stroke
o Haemorrhagic stroke (subarachnoid or intracerebral)
Contra indications for MRI/DCE-MRI
o Heart valve prosthesis
o Pacemaker
o Intracerebral clips (aneurysm)
o Intra-ocular metal pieces
o Cochlear implant
o Claustrophobia
o Poor kidney function (GFR<30ml/min)
o Previous allergic reaction to contrast agent (gadobutrol)
Psychiatric disorders associated with (temporarily) cognitive decline (e.g. depression, psychosis);Group specific exclusion criteria:
Lacunar stroke
- Potential cardiac embolic source (e.g. atrial fibrillation)
- Stenosis of >=50% of one or both internal carotid arteries.
Mild cognitive impairment due to cSVD
- Clinical and/or subclinical cortical events
- Other causes for cognitive impairment (e.g. Alzheimers Disease)
Healthy subjects
- Clinically overt cardiovascular diseases
- Clinically overt cerebrovascular diseases
- Disease of the central nervous system (e.g. Multiple Sclerosis, brain tumor/metastasis)
- Extensive structural lesions on MRI associated with cSVD
- Cognitive impairment (i.e. objective and/or subjective cognitive deficits).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL41952.068.12 |
| OMON | NL-OMON26559 |