The main objective of the study is to investigate MEG-based hippocampal and whole brain neuronal hyperactivity in preclinical DIAD mutation carriers and to find proof-of-concept for the translatability of findings from preclinical AD mouse models to…
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Neurological disorders NEC
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Hippocampal and global brain MEG based measures of oscillatory brain activity,
represented in total broadband power and E/I balance (from 1/f of the
powerspectrum or new method for fE/I, based on DFA and power.
Secondary outcome
MEG-based measures of:
- oscillatory activity, represented in (average) peak frequency and relative
power of the following frequency bands: theta (4-8 Hz), alpha (8*13 Hz), beta
(13-30 Hz), and gamma (30-48Hz).
- functional connectivity between target regions in specific frequency bands,
expressed as amplitude envelope correlation corrected (AECc) for volume
conduction.
- functional network measures by the use of graph theoretical measures,
including degree, modularity, path length, betweenness centrality.
Structural MRI:
- Structural connectome
- Grey & White matter volumes
- White matter integrity & microbleeds
Neuropsychological performance
- Scores from different tests will be used as indices of cognitive performance
on different domains
- Score of the working memory task during the MEG recording will be used as
indicator for working memory
Background summary
Despite decades of research, the pathophysiology of Alzheimer*s disease (AD)
remains poorly understood and effective treatment is still not available. AD
has a long prodromal phase and clinical signs become apparent only decades
after onset of the disease. Detailed characterization of this preclinical
disease stage holds the key to early diagnosis and intervention. Recent studies
suggest that neuronal excitation/inhibition (E/I) imbalance in and network
hyperexcitability are early signs of AD. Alterations in neuronal E/I ratios and
network function can in principle be detected with non-invasive electro- or
magnetoencephalography (M/EEG), but robust M/EEG markers for early AD are still
not available. This study will characterize neurophysiological alterations in
early brain network function of truly preclinical AD patients, in particular
dominantly inherited Alzheimer's Disease (DIAD) mutation carriers, and aims to
find proof-of-concept for translatability of findings in rodents to humans.
Study objective
The main objective of the study is to investigate MEG-based hippocampal and
whole brain neuronal hyperactivity in preclinical DIAD mutation carriers and to
find proof-of-concept for the translatability of findings from preclinical AD
mouse models to findings from the clinic.
In addition, we will asses whether similar alterations in MEG-based measures of
brain activity of DIAD mutation carriers can be found in the early phase of
sporadic Alzheimer's disease (using available cohortdata).
Also, computer models and in vitro investigations of induced pluripotent stem
cell-derived neuronal networks will help to find mechanistic explanations for
changes in brain activity underlying the earliest changes in AD on a
multi-level.
Study design
Proof-of-concept, cross-sectional observational study.
Study burden and risks
This study will take approximately 3.5 hours and participants will be asked to
come to the AUMC, location VUmc to undergo an MEG recording as well as MRI
scan. Participants will also complete a neuropsychological test and additional
questionnaires regarding their mental health among other subjects of which the
risk is considered neglegible. The main procedures, i.e. MEG and MRI
recordings, are non-invasive and involves lying in a supine position in a
shielded room. Thede procedures (45-60 minutes for MEG and 30 minutes for MRI)
are not painful in any way, are not considered to be difficult or stressful
(except for patients with extreme claustrophobia), and has negligible risks.
MRI scanning may have a risk of chance findings. Skin biopsy is a regular
medical procedure often used in the clinic and has minimal risk of bleeding,
hyperreactivity to local anaesthetics or scar formation. There is no individual
benefit from participation in the study.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Potential subjects need to have a dominantly inherited Alzheimer's Disease
(DIAD) mutation and must be at least 18 years of age.
Exclusion criteria
Participants who show dementia due to (familial) AD will be excluded from the
study. In addition, participants who have for example cardiac pacemakers, ICD's
or other intracorporal devices which excessively interfer with MEG-signals may
be excluded.
Additional contra-indications for MRI scanning (e.g. implanted metals), current
or planned pregnancy and subjects with severe claustrophobia cannot
participate.
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 | NL70688.029.20 |