To investigate longitudinal changes in VR in patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and AD dementia compared with controls. To investigate whether VR predicts progression of disease severity (cognitive…
ID
Source
Brief title
Condition
- Other condition
- Vascular haemorrhagic disorders
Synonym
Health condition
hersenaandoening
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) 3T MRI: the amplitude of the BOLD response in percentage signal change
between stimulus on and off, time-to-peak response (sec), and time-to-baseline
(sec) after discontinuation of the visual stimulus, classic signs of CAA
(intracranial hemorrhage, lobar microbleeds, subarachnoidal hemorrhage and
superficial siderosis) and SVD markers (number of small subcortical infarcts
and lacunes, volume of white matter hyperintensities (WMHs), perivascular
spaces in the basal ganglia and centrum semiovale, number and location of deep
microbleeds and grey matter volume). 2) Neuropsychological assessment 3)
Baseline characteristics, 4) DNA: APOE * genotype.
Secondary outcome
NA
Background summary
Cerebral amyloid angiopathy (CAA), a common cerebrovascular small vessel
disease (SVD),is a frequently (98%) found co-morbidity at autopsy in patients
with Alzheimer*s disease (AD). Current in vivo hallmarks of CAA represent
changes relatively late in the disease process and leaves CAA in AD often
undetected. Recently, we found that decreased vascular reactivity (VR) measured
with blood oxygen level dependent (BOLD) MRI, after visual stimulus, is an
early CAA marker. In my previous research (P19.039), I used BOLD-MRI to detect
decreased VR in different stages of AD, showing that increasing stages of AD
associate with decreasing VR independent of age, classic SVD markers and
atrophy. Moreover our data show that VR is associated with cognitive deficits.
Therefore, cross-sectional data indicate that decreased VR is an important
co-morbidity already in early stages of AD with an independent effect on
disease severity. In this respect, we aim to determine the decrease of VR in
both controls and (early stage) AD patients to monitor AD disease progression.
This is an essential step to aid in the development and application of
effective treatment as it is expected that CAA can cause/worsen AD pathology.
Study objective
To investigate longitudinal changes in VR in patients with subjective cognitive
impairment (SCI), mild cognitive impairment (MCI) and AD dementia compared with
controls. To investigate whether VR predicts progression of disease severity
(cognitive decline) over a time period of 3 years and to investigate if
decreased VR at baseline predicts increasing severity of other MRI markers for
AD and SVD-markers at follow-up.
Study design
an longitudinal observational case - control study.
Study burden and risks
This is a non-therapeutic group relatedness study in only capacitated subjects.
In order to achieve the aim of the study AD patients are needed. Vascular
reactivity has potential to determine the role of the vascular aspects in AD.
The risks of this research are minimal (risk of every day life), because there
are no consequences to the health of the participant. We will keep the charges
at a minimum. The research will consist of a 60 minutes MRI scan, a
neuropsychological assessment of 1 hour and collection of 2 ml saliva (if not
already collected at baseline).
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
inclusion all of the following criteria. For this study three different routes
for inclusion exists. Inclusion criteria for each group separately are shown
below.:
1. Participants who were included in our previous CASCADE study (P19.039).
* Capable of giving informed consent (see appendix)
2. Patients who attended the memory clinic of the Leiden University Medical
Center/ Haaglanden MC within one year ago
• Diagnosed with (mixed) probable AD
• Diagnosed as MCI
• Diagnosed as SCI
• Age between 50-90 years
• Capable of giving informed consent (see appendix)
3. Control subjects
• Healthy adults without memory complaints
• Age aged between 50-90 years old
• Capable of giving informed consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study. For this study three different routes for
inclusion exists. Exclusion criteria for each group separately are shown below.
1. Participants who were included in our previous CASCADE study (P19.039).
• No MRI at previous CASCADE study (P19.039)
2. Patients who attended the memory clinic of the Leiden University Medical
Center/Haaglanden MC within one year ago
- Contra-indication to MRI scanning:
• Claustrophobia
• Pacemakers and defibrillators
• Nerve stimulators
• Intracranial clips
• Intraorbital or intraocular metallic fragments
• Cochlear implants
• Ferromagnetic implants
• Hydrocephaluspump
• Intra-utrine device (not all types)
• Permanent make-up
• Tattoos above the shoulders (not all)
- Specific contraindications to fMRI
• Seizure within prior year.
• Noncorrectable visual impairment.
- MMSE < 19 points (measured at moment of screening or at memory clinic with a
maximum of 6 months in retrospect) (this cutoff was also used in the Leiden
85-Plus study14)
- Severe physical restrictions (completely wheelchair dependent)
- Age above 90
3. Control subjects
- Contra-indication to MRI scanning:
• Claustrophobia
• Pacemakers and defibrillators
• Nerve stimulators
• Intracranial clips
• Intraorbital or intraocular metallic fragments
• Cochlear implants
• Ferromagnetic implants
• Hydrocephaluspump
• Intra-utrine device (not all types)
• Permanent make-up
• Tattoos above the shoulders (not all)
- Specific contraindications to fMRI
• Seizure within prior year.
• Noncorrectable visual impairment.
- MMSE < 19 points (measured at moment of screening or at memory clinic with a
maximum of 6 months in retrospect) (this cutoff was also used in the Leiden
85-Plus study14)
- Severe physical restrictions (completely wheelchair dependent)
- Age above 90
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | NL83653.058.23 |