Hypotheses are that vascular reactivity decreases (slower time-to-peak, slower time-to-baseline and lower amplitude of the BOLD response) with increasing dementia severity (SCI-MCI-LOAD/VaD). In MCI and SCI, we expect a decreased vascular reactivity…
Bron
Verkorte titel
Aandoening
dementia
Ondersteuning
Onderzoeksproduct en/of interventie
Geen registraties gevonden.
Uitkomstmaten
Primaire uitkomstmaten
The change in BOLD signal in response to visual stimulation including 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 will be analyzed.4, 5 Only normal appearing tissue will be taken for analysis.
Achtergrond van het onderzoek
Rationale: In patients with Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA) is a frequently found co-morbidity at autopsy. Post-mortem studies have shown that up to 98% of AD patients show moderate to severe CAA, however currently clinical data are limited. Recent research shows a prominent role of vascular damage as first hallmark of AD. Therefore, detection of CAA in patients with AD offers increased insight into etiology of AD, and is expected to be helpful in the development of efficient therapies against AD. Vascular reactivity measured with BOLD MRI is a sensitive quantitative marker of vessel damage in hereditary CAA, even before classical radiological hallmarks of the disease become overt. This opens the possibility to study early, or subtle, manifestations of CAA as comorbidity in AD at several stages of the disease. Hypotheses are that increasing dementia severity associates with decreasing vascular reactivity.
Objective: 1. To determine whether vascular reactivity is lowered in memory clinic patients with mixed and pure AD pathology. 2. To define whether vascular reactivity upon visual activation is associated with CAA or with other small vessel disease (SVD) neuroimaging markers and cardiovascular risk factors. 3. To establish whether vascular reactivity is independently associated with (additional) cognitive deficits.
Study design: Observational cross sectional case-control study.
Study population: 40 Early onset AD (age of onset ≤ 65 years), 40 Late onset AD (age of onset > 65 years), 40 Vascular dementia patients, 40 patients with mild cognitive impairment and 40 patients with subjective cognitive impairment plus controls, i.e. 200 patients from the memory clinic and 80 controls to cover the total age range.
Main study parameters/endpoints: 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 microbleeds and grey matter volume). 2) Neuropsychological assessment 3) Baseline characteristics, 4) DNA: APOE ε genotype.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: 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 only consist of a 30-45 minutes MRI scan, a neuropsychological assessment of 1 hour (if not already performed at memory clinic) and collection of 2 ml saliva.
Doel van het onderzoek
Hypotheses are that vascular reactivity decreases (slower time-to-peak, slower time-to-baseline and lower amplitude of the BOLD response) with increasing dementia severity (SCI-MCI-LOAD/VaD). In MCI and SCI, we expect a decreased vascular reactivity compared to controls. In pure AD (EOAD), no vascular damage is expected.
Onderzoeksopzet
one time-point
Onderzoeksproduct en/of interventie
none
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
In order to be eligible to participate in this study, a subject must meet the following criteria:
Patients who attended the memory clinic of the Leiden University Medical Center/ Bronovo hospital within one year ago
• Diagnosed with probable AD
• Diagnosed as MCI
• Diagnosed as SCI
• Diagnosed as VaD
• Capable of giving informed consent (see appendix)
Control subjects
• Healthy adults without memory complaints aged between 40-90 years old
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- 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 study30)
- Severe physical restrictions (completely wheelchair dependent)
- Age above 90
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
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In overige registers
Register | ID |
---|---|
NTR-new | NL8045 |
Ander register | METC LDD : P19.039 |