We will investigate the relationship between this permeability measure and (i) cognitive performance and (ii) the status of MRI visible cerebrovascular pathology (i.e. white matter hyperintensities, lacunar infarctions, microbleeds) in the most…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
neurodegeneratieve aandoeningen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study measures are blood brain barrier permeability as measured by
T1-weighted dynamic contrast MRI; and cognitive performance as measured by the
neuropsychological assessment of the standard diagnostic procedure of the
memory clinic, including global cognition (Mini Mental State examination),
memory performance (Verbal Learning Test), mental speed (Letter Digit
Substitution Test), and attention (Stroop task and Concept Shifting Test).
Another outcome measure is the status of MRI visible cerebrovascular pathology
(i.e. white matter hyperintensities, lacunar infarctions, microbleeds).
Secondary outcome
Gray matter atrophy
Background summary
Alzheimer*s disease (AD) and vascular dementia (VaD) are the most common forms
of dementia. Yet, the cause of these diseases is still unknown. A potentially
important initiating factor is a disrupted blood-brain barrier. This can
initiate cerebral microangiopathy, which has frequently been associated with
VaD. Nevertheless, also in most AD patients a substantial increase of vascular
damage has been observed. The present study investigates the correlation
between blood-brain-barrier breakdown and cognitive decline in AD and VaD. An
innovative dynamic contrast-enhanced MRI scan that has recently been developed
and tested at our institute, will be used to measure blood-brain barrier
permeability (see previous METC dossier no NL36156.068.11).
Study objective
We will investigate the relationship between this permeability measure and (i)
cognitive performance and (ii) the status of MRI visible cerebrovascular
pathology (i.e. white matter hyperintensities, lacunar infarctions,
microbleeds) in the most common forms of dementia.
Study design
The present study is a cross-sectional observational MRI study.
Study burden and risks
Individuals with contraindications for MRI and the contrast agent Gadovist
(eGFR > 30 mL/min) will be excluded. Risks associated with participants are
therefore negligible. The burden for patients is restricted to two test
sessions. The first test session lasts approximately 85 minutes and includes a
1-hour MRI scan (max. 45 minutes scanning plus preparations), blood pressure
measurement and blood tests for haematocrit levels and ApoE genotype. The
second test session includes a 1-hour MRI scan (max. 45 minutes scanning plus
preparations) with contrast administration. From the standard diagnostic
procedure of the memory clinic, we will obtain performance on
neuropsychological tests, blood creatinine level and clinical history. Healthy
control participants will follow the same procedure; except that the first test
session lasts 100 minutes (including also a blood creatinine test and clinical
history) and the second session lasts 120 minutes (including also
neuropsychological tests).
From experience with our previous study NL36156.068.11, we know that this is
doable for patients.
For the 20 participants who will be invited for the follow-up examination, we
will plan two sessions: the first session lasts 15-75 minutes (depending on the
need of a neuropsychological assessment), the second session consists of the
MRI scan en will last 75 minutes (actual scanning takes maximally 55 minutes).
Participants who agree to undergo an additional scan 2-4 hours later, will have
an additional 20 minutes MRI scan.
Dr. Tanslaan 12
Maastricht 6229ET
NL
Dr. Tanslaan 12
Maastricht 6229ET
NL
Listed location countries
Age
Inclusion criteria
Patients (baseline):
* Informed consent before participation in the study
* Age of 55 and older
* Diagnosed with AD, VaD, mixed AD and VaD, mild cognitive impairment, vascular cognitive impairment and subjective cognitive impairment
* MMSE * 20 and patients are mentally competent (in general, individuals with an MMSE *18 are considered mentally competent) ;Healthy participants (baseline):
* Informed consent before participation in the study
* Age of 55 and older
* No Diagnosis of dementia, prodromal dementia, or mild cognitive impairment.
* MMSE * 26
* No substantial memory complaints (according to participant)
* Average age, gender and education is similar to the patient groups.;Follow-up participants with leakage:
* Informed consent before participation in the follow-up study
* MMSE * 20
* Participation in baseline study
* Blood-brain barrier leakage is apparent on baseline post-contrast FLAIR sequence ;Follow-up participants without leakage:
* Informed consent before participation in the follow-up study
* MMSE * 20
* Participation in baseline study
* Blood-brain barrier leakage is not apparent on baseline post-contrast FLAIR sequence
* Average age, gender and diagnosis is similar to the follow-up participants with leakage group.
Exclusion criteria
* Contraindications for MR scanning (e.g. brain surgery, cardiac pacemaker, metal implants, claustrophobia, large body tattoos)
* Contraindications for contrast agent Gadovist (renal failure) as determined by the estimated Glomular Filtration Rate eGFR < 30 mL/min; or known allergy to Gadovist.
* Major vascular disorders (e.g. stroke<3 months ago, unstable heart disease <3 months ago. Because AD and VaD and their preceding stages are associated with both stroke and heart disease (such as myocardial infarction) we will exclude participants when these occurred <3 months before inclusion).
* Psychiatric or neurological disorders: Major depression (< 12 months); history of schizophrenia; bipolar disorder; psychotic disorder NOS or treatment for a psychotic disorder (< 12 mnd); epilepsy; Parkinson*s disease; MS; brain surgery; brain trauma; electroshock therapy; kidney dialysis; Meniere*s disease; and brain infections.
* Structural abnormalities of the brain
* Absence of reliable informant (for patient groups)
* cognitive impairment due to alcohol abuse or other substances
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 |
|---|---|
| Other | Bij clinicaltrials.gov: Protocol ID NL46089.068.13 |
| CCMO | NL46089.068.13 |