The cardiac contribution to cerebral perfusion - 'the heart-brain axis'

Cardiovascular disease is associated with loss of cognitive functioning. Both
conditions are more common in elderly people. The condition of the heart and
the large vessels determines the flow of blood to the brain and we suppose a
larger role of the heart than previously is assumed. According to the
traditional paradigm of cerebrovascular autoregulation in humans, the cerebral
perfusion (e.g. cerebral blood flow (CBF)) is largely influenced by the
cerebral perfusion pressure (CPP). The CPP, in turn, mainly depends on changes
in cerebrovascular resistance. According to the classical model of
autoregulation, CBF is maintained constant within a wide range of CPP. However,
we and others have demonstrated in the past period that a decline in perfusion
pressure within the cerebral autoregulatory range can lead to a decrease in
CBF.
The prevalence of cardiovascular disease in relation to cognitive decline
increases with age. Knowledge about the effect of ageing on the relationship
between systemic (baroreflex) and cerebrovascular control mechanisms (mechanic-
and chemo regulation), CPP and systemic blood flow is, however, incomplete.
This impedes the development of new therapeutic strategies about treatment and
prevention of loss of cognitive functioning. This study investigates the effect
of ageing on the relationship between the systemic and cerebrovascular
circulation combining state of the art techniques (ultrasound, ultra-high field
(3T) MRI).

Answering the question about the influence of ageing on the relationship
between systemic flow and pressure on the one hand and cerebral perfusion on
the other hand.

Before the start of the study (study phase), the subjects will be medically
screened. This study consists of two pilot- and one study phase. In the first
pilot phase, the different protocols as described in the study phase will be
tested (inlcuding LBNP and handgrip exercise). During the second pilot phase,
we will refine the protocol and investigate the reproducibility. In both the
pilot as in the study phase, the same protocols will be tested and the same
parameters will be measured.

The cerebral perfusion is evaluated in both the AMC Laboratory for Clinical
Cardiovascular Physiology and in the LUMC Gorter center. Brain blood flow
(velocity) will be qualified with Doppler ultrasound and ASL (arterial spin
labeling) techniques on two different measurement days. Subsequently, the
(baroreflex mediated) sympathetic and parasympathetic cardiovascular control
will be compared in both young and elderly subjects during postural load
together with quantification of the cerebrovascular mechanic- and
chemoregulation.

There are no foreseen risks with participating in this study (for both pilot as
study phase). The burden for the subject is minimal because almost all
measurements done in this study are non-invasive (except for MRI
meausurements). The physical load of the routine tests in this study is
generally well tolerated. During the entire study, the subject will
continuously be monitored to ensure subjects safety. The medical screening
prior to the study is of great scientific interest. There are also no foreseen
risks during the medical screening.