Primary objective: describe the longitudinal changes of Aβ38, Aβ40, Aβ42, and Aβ43 concentrations in CSF of patients with CAA, AD, and healthy control cases and estimate the differences in change between those…
ID
Source
Brief title
Condition
- Other condition
- Cranial nerve disorders (excl neoplasms)
- Vascular haemorrhagic disorders
Synonym
Health condition
Dementie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective:
Describe the longitudinal changes of Aβ38, Aβ40, Aβ42, and Aβ43 concentrations
in CSF of patients with CAA, AD, and healthy control cases and estimate the
differences in change between those groups.
Secondary outcome
1. Quantified volume of cerebral perivascular gadolinium signal and structural
features in CAA patients
2. Biomarker assays for BBB-dysfunction detection
3. Correlations between biomarker concentrations with Aβ in the study
populations
4. Correlation between biomarker concentrations and gadolinium signal
5. Correlation analysis between APOE and BBB-dysfunction biomarker and the Aβ
peptides
Background summary
We have recently described that different forms of the amyloid beta peptide,
Aβ38, Aβ40, Aβ42, and Aβ43, have different concentrations in cerebrospinal
fluid (CSF) when cross-sectionally compared between (Dutch-type) Cerebral
amyloid angiopathy ((D-)CAA), Alzheimer*s disease (AD), and healthy control
patients (de kort, et. al. 2022). These peptides and other toxic molecules are
cleared from the brain by the blood brain barrier (BBB). Despite being studied
extensively at a single time point, the temporal changes in concentrations is
currently unknown in both the pathophysiological and physiological context.
Furthermore, it is unclear if concentration changes are correlated with the
dysfunction of the BBB due to the lack of adequate BBB-monitoring biomarkers.
Describing the longitudinal changes of amyloid-beta in CSF of CAA and AD
patients will provide additional insights in the mechanisms of these
neurodegenerative diseases. Moreover, early stage changes of concentraties
could function as earlie stage diagnostic tool for CAA and/or AD. This is
benefitial with the prospect of novel treatments targeting amyloid-beta.
Furthermore, monitoring these peptides overtime during disease can be used as
additional prognostic biomarker.
Describing BBB-dysfunction with the use of biomarkers has potential to
elucidate the ethiology and progressive character of CAA, AD and potentially
other neurodegenerative diseases. In addition, these biomarker could play an
assisting role in therapydesicion or early detection of intracerebral
heamorraghes.
Study objective
Primary objective: describe the longitudinal changes of Aβ38, Aβ40, Aβ42, and
Aβ43 concentrations in CSF of patients with CAA, AD, and healthy control cases
and estimate the differences in change between those groups.
1. Explorative study to establish brain (micro)structure and vascular function
measured with MRI in the CAA and control study
populations.
2. Develop robust assays for quantification of novel CSF and blood biomarkers
indicating BBB impairment.
3. Explorative cross-sectional study to describe if the Aβ peptide
concentrations correlate with the measured BBB-dysfunction
biomarkers and if these correlations differ between the study populations.
4. Explorative cross-sectional study to describe if the Aβ peptide and
BBB-dysfunction biomarker concentrations correlate with BBB-dysfunction
measured with DCE-MRI in the CAA and control study populations.
5. Explorative cross-sectional study to describe if the variants in the APOE
gene have a correlation with the measured Aβ peptides
and BBB-dysfunction biomarker(s).
Study design
Longitudinal cohort study with at least two years interval.
Study burden and risks
Patiënts are asked to undergo a lumbal puncture, venipuncture, and a cognitive
test.
A part of the studypopulation, those who participated in either the BIONIC or
CAFE study, will be invited one visit. For this population the baseline visit
was during these studies and therefore the second visit is scheduled.
Therefore, these participants will only undergo above mentioned procedures
once.
The participants who had not participated in the BIONIC or CAFE study will be
asked to visit twice with an interval of two years. The participant will under
go above mentioned procedures once at both the baseline visit and at the second
visit.
For the lumbar puncture the participant is asked to lie sideways with knees
towards the chest, similar to the feutus position. Next, the medical
professional will puncture the lowerback, here is a sack located containing
cerebrospinal fluid. Damaging of the spinal cord is avoided by performing the
puncture at this position at the lowerback since there is no spical cord
located here.
Some people develop post-puncture headaches. Most often do these complains
subside when the participants lies down. For a small percentage these headaches
could occure for several days. This occurs for approxemately 4% of the patients
when using an atraumatic needle. To reduce the chance of headache development;
a 20-gauge neelde is used as well. In addition, the participant is adviced to
consume caffein containing drinks in addition to drinking a proper amount of
water. The occurance of a heamorage or infection is extemely rare (<0.1%). To
minimize the occurance are both the skin and materials desinfected.
The skin around the puncture site is temporately and locally numbed to reduce
discomfort of the participant.
During the venipuncture a vene in the anterior of the elbow is used to obtain
blood. This is routinely performed by the medical professional and the risks
are negligible.
The cognitive test in this study is the Dutch equivalent of the MoCA test. The
duration of this test is around 10 minutes.
The observed side-effects of Gadovist administration are: headache, nausea,
injection site reactions, disturbed sense of taste and
hot feeling (from >= 1/1000 to < 1/100 cases).
The overall risk of this study is estimated as "negligible".
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Patients with CAA:
To be eligible to participate, a subject must meet the following criteria:
1) Fulfilment of the Boston criteria 2.0 for CAA;
2) Subjects are mentally competent to take a decision on participation;
3) Most recent ICH was at least 6 months ago;
4) Age >50 years;
5) Written informed consent;
6) If participant participated in the BIONIC/CAFÉ study: Lumbar puncture at
baseline visit successfully acquired CSF.
Patients with AD:
To be eligible to participate, a subject must meet the following criteria:
1) Fulfilment of the NIA-AA criteria for probable AD.
2) Subjects are mentally competent to take a decision on participation;
3) Written informed consent;
4) Age >50 years;
5) If participant participated in the BIONIC/CAFÉ study: Lumbar puncture at
baseline visit successfully acquired CSF.
Control cases:
To be eligible to participate, a subject must meet the following criteria:
1) Age >50 years;
2) A MoCA score >=27
3) Subjects are mentally competent to take a decision on participation;
4) Written informed consent
Exclusion criteria
Exclusion CAA:
1) Presence of blood coagulopathy, established by medical history;
2) History of major psychiatric disorder;
3) Pregnancy at time of study participation;
4) Allergy to local anesthetic agents;
5) Contra-indication for lumbar puncture: medical history of compression of
spinal cord, spinal surgery, skin infection, developmental abnormalities in
lower spine;
6) Subjects who are currently participating in another study or have
participated in a clinical study within the previous 30 days, based on their
own report;
7) Subjects with a history or current drug or alcohol abuse;
8) Subjects who are part of the study staff personnel or family members of the
study staff personnel.
9) Proven mutation carrier for the D-CAA (tested only on clinical indication)
10) Contra-indications for MRI
Exlcusion AD:
1) Presence of blood coagulopathy, confirmed by medical history;
2) History of major psychiatric disorder;
3) Pregnancy at time of study participation
4) Allergy to local anesthetic agents;
5) Contra-indication for lumbar puncture: medical history of compression of
spinal cord, spinal surgery, skin infection, developmental abnormalities in
lower spine;
6) Subjects who are currently participating in another study or have
participated in a clinical study within the previous 30 days, based on their
own report ;
7) Subjects with a history or current drug or alcohol abuse;
8) Proven mutation carrier for a gene known to be associated with early-onset
hereditary AD (tested only on clinical indication)
9) Subjects who are part of the study staff personnel or family members of the
study staff personnel.
Exclusion control cases:
1) Self-reported (subjective) cognitive decline;
2) History of major neurological (e.g. stroke, neurodegenerative disease, brain
tumours, brain infection or inflammation) or psychiatric disorder;
3) Pregnancy at time of study participation
4) Presence of blood coagulopathy, confirmed by medical history;
5) Allergy to local anesthetic agents;
6) Contra-indication for lumbar puncture: medical history of compression of
spinal cord, spinal surgery, skin infection, developmental abnormalities in
lower spine;
7) Subjects who are currently participating in another study or have
participated in a clinical study within the previous 30 days, based on their
own report ;
8) Subjects with a history or current drug or alcohol abuse;
9) Proven mutation carrier for a gene known to be associated with early-onset
hereditary AD (tested only on clinical indication) or D-CAA
10) Subjects who are part of the study staff personnel or family members of the
study staff personnel.
11) Contra-indications for MRI
Design
Recruitment
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 |
|---|---|
| CCMO | NL85709.091.23 |