The dynamic effects of hypertension on the brain and its vessels

High blood pressure and specifically hypertension affects many people in the
population and is the largest contributor to global mortality. Moreover
hypertension has many devastating consequences ranging from kidney failure to
stroke and death. The damage caused by hypertension gradually evolves and is
often found when damage already happened. Despite these consequences, it is
poorly understood how hypertension is initiated and what the global
consequences are of hypertension on the brain and vessels, also on a diurnal
level. Furthermore midlife high blood pressure is a well-known risk factor for
cerebrovascular diseases, ultimately leading to cognitive decline at an older
age. As such, antihypertensive medication is suggested to be protective for
cognitive brain changes.

Recent research in mice showed that sleep is important for restoring the brain.
During our night-time the interstitial space increased with more than 60%
resulting in better perfused tissue by CSF. The exchange of interstitial fluid
and CSF enables toxins and waste products of metabolites to be drained from the
brain into the perivascular spaces and ultimately into the lymphatic system.
This brain drainage system is now known as the *glymphatic system*. It is
indicated that the glymphatic function is suppressed in various disease. This
reduction in function may lead to accumulation of protein aggregation and seems
to follow the day-night cycle. Even so, failure of the drainage system may
contribute to the development of neurodegenerative disease, but also to brain
injury and stroke. Since we know that this system exists it may be hypothesized
that differences in brain volume and CSF may be found between day and
night-time as a result of different glymphatic activity. One of the diseases
suggested to be affecting the glymphatic system is stroke. Since hypertension
is the utmost important risk factor of stroke and glymphatic function probably
fails in stroke, it may be suggested that hypertension directly acts on this
system.

Our research aim is fourfold:
1) We aim to assess the effect of hypertension on functional and structural
markers of the brain using 3 tesla (T) and 7T MRI in patients who are temporary
drug naïve and will be switched-on to medication as part of their regular
clinical work-up.Therefore baseline scans (without medication) will be compared
to follow-up scans (with medication) in patients.
2) Functional and structural markers of the brain in patients at baseline will
be compared to these markers in healthy volunteers at baseline using 3T and 7T
MRI.
3) In a subset (1/3) of patients and (1/3) healthy volunteers we will also
assess the circadian rhythm of these functional markers using 3T MRI.
4) To obtain a basic understanding of the possible clinical and subclinical
consequences of hypertension, we will also perform neuropsychological tests in
all subjects.

This study is designed as a single-center prospective case-control study. MR
imaging at baseline and after three months will be performed with a 3T MRI
system in patients with hypertension who are temporary medication naïve as part
of their regular clinical care. A second MRI exam will be performed at 7T, also
at baseline and after three months. In healthy volunteers only the baseline
scans (one at 3T and one at 7T) will be obtained. One third of the volunteers
will be asked to come back in the afternoon for an additional 3T MRI to obtain
information about circadian rhythms.

Baseline characteristics of all subjects will be collected during inclusion of
this study. 3T MRI exams will be acquired before the start of medication and
within three months when patients are switched-on antihypertensive medication
as part of their regular clinical care. 7T MR imaging will be performed within
one week after the first and second 3T MRI scan. A third of the volunteers will
be asked to come back in the afternoon for an additional 3T MRI to obtain
information about circadian rhythms.

The radiologist and a second (scientific) observer will be blinded for clinical
information.

During the MRI, patients are exposed to strong magnetic fields and radio waves.
In normal clinical practice, MRI is very
often used. There are no harmful effects on the human body determined. In some
cases, people experience flashes of
light, tingling and transient dizziness. These are always during the scan and
disappear immediately after scanning.
Implanted medical devices might become disturbed by the magnetic field. People
with medical implants are therefore
not considered for the study.