Objective: to provide an answer to the following question: in patients with AD, does treatment with a ChEI improve cerebral autoregulation?
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Dementia and amnestic conditions
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective: to test the hypothesis that ChEI*s augment cerebral
autoregulation in patients with AD. To test this hypothesis, we will
continuously monitor CBF together with BP before and during treatment with
ChEI*s in patients with AD.
Primary outcome parameter: dynamic cerebral autoregulation, quantified by the
parameter *phase lead*.
Explanatory note on cerebral autoregulation and vasomotor reactivity
Dynamic cerebral autoregulation will be quantified by transfer function
analysis based on spectral analysis of induced oscillations in beat-to-beat
changes in CBF-velocity, recorded by TCD, and beat-to-beat changes in blood
pressure, recorded by Finapres. The transfer function between BP and
CBF-velocity will be characterized by the parameters phase lead and gain. The
gain quantifies the damping effect of dynamic CA on changes in BP and marks the
efficiency of the response, whereas phase shifts can be considered surrogate
measures for the time delay of the autoregulatory response. A positive phase
shift indicates that oscillations in CBF-velocity lead oscillations in BP;
changes in CBF-velocity recover faster than changes in BP and this is
interpreted as intact dynamic CA.
Cerebral vasomotor reactivity is defined as the cerebrovascular response to
changes in arterial carbon dioxide (CO2), a potent cerebral vasodilator.
Hypercapnia augments CBF, whereas hypocapnia reduces CBF. Hypocapnia is induced
by hyperventilation, hypercapnia is induced by inhalation of room air, enriched
with 7 % CO2. Vasomotor reactivity will be expressed as the percentage changes
in CBF-velocity.
Secondary outcome
-dynamic cerebral autoregulation, quantified by the parameter *gain*
-vasomotor reactivity
Background summary
Rationale: Cholinesterase-inhibitors (ChEI*s) are drugs used to treat symptoms
of Alzheimer*s disease (AD), which is characterized by a progressive
cholinergic deficit. The central theory of this explorative study is that
ChEI*s directly act to augment cerebral autoregulation. Consequently, we
hypothesise that a vascular mechanism is responsible for most of the observed
clinical effects of ChEI*s in patients with AD. This theory is closely related
to recent insights in the contribution of cerebral vascular disease to the
pathogenesis of AD, known as the vascular hypothesis of AD. Central to both the
vascular hypothesis and our new theory are the common findings of
cerebrovascular lesions in the brains of AD patients, and the high prevalence
of cardiovascular risk factors in these patients. In our hypothesis, the
cholinergically-mediated vascular effects include an improvement of cerebral
autoregulation.
Study objective
Objective: to provide an answer to the following question: in patients with AD,
does treatment with a ChEI improve cerebral autoregulation?
Study design
The design of this explorative pilot study, is an open-label design.
Study burden and risks
This study includes diagnostic tests that are included in, or closely resemble,
the standard diagnostic and therapeutic approach to patients with Alzheimer*s
disease at our institution. Extra burden for patients consists of two repeated
site visits during which we will monitor cerebral blood flow, blood pressure
and cortical oxygenation. These tests are non-invasisve and pose no health
risks. The study drug is approved for use in Alzheimer*s disease.
P.O. Box 9101
6500 HB Nijmegen
NL
P.O. Box 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Meeting DMS-IV R criteria for dementia
meeting NINCDS-ADRDA criteria for probable AD
clinical dementia rating scale (CDR) 0.5 - 2
Exclusion criteria
Contra-indication for or unwilling to receive treatment with cholinesterase inhibitors
major cerebrovascular disease (stroke)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005426-71-NL |
| CCMO | NL19922.091.07 |