Main objective of the study is to define an algorithm based on the plasma biomarkers: A*40, A*42, t-Tau, p-Tau, NfL and APOE * status and NeuroCart tests, age, grip strength and level of education that distinguishes between positive and negative A*…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Neurodegenerative disorders
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
NeuroCart assessments
- Adaptive tracking test;
- Visual Verbal Learning Test (VVLT);
- Milner Maze test;
- Face encoding and recognition test;
- N-back test;
- Sustained Attention to Response test (SART);
- Finger tapping.
Neurophysiological NeuroCart assessments
- 21 leads electroencephalogram (EEG);
- Smooth and saccadic eye movement.
Neuropsychological tests
- Clinical Dementia Rating scale (CDR);
- Instrumental Activities of Daily Living scale (IADL).
Handgrip strength
- JAMAR hydraulic hand dynamometer
Biochemical outcome variables
CSF biomarkers
- A* concentration (1-40, 1-42 and 1-42/1-40 ratio);
- T-Tau and p-Tau concentrations;
- NfL concentration.
Plasma biomarkers
- A* concentration (1-40, 1-42);
- T-Tau and p-Tau concentrations;
- NfL concentration.
Genetics
- APOE * genotype.
Secondary outcome
Exploratory biomarkers including but not limited to:
- Synaptic loss; Neurogranin [24],
- Glial inflammation; YKL-40 [25],
- Levels of p-Tau181 in extracts of neutrally-derives blood exosomes [26],
- MicroRNAs [MiR-155, MiR-107 and MiR-29 [27]]).
Background summary
While the definite diagnosis for AD can only be made post-mortem by
investigating the presence of amyloid beta (A*) plaques and neurofibrillary
tangles, recent advances in neuroimaging, cerebrospinal fluid (CSF) assays, and
other fluid biomarkers now provide the ability to detect evidence of the AD
pathophysiological process in vivo [3]. Furthermore, emerging data in otherwise
healthy elderly individuals suggest that biomarker evidence of A* accumulation
and neurofibrillary tangles are associated with functional and structural brain
alterations, consistent with the patterns of abnormality seen in patients with
mild cognitive impairment (MCI) and AD prior to the clinical expression of
symptoms [4]. These observations are confirmed by clinical cohort studies which
suggest that there may be very subtle cognitive alterations that are detectable
years before meeting clinical criteria for MCI, and which predict progression
to AD [5].
Based on extensive longitudinal biomarker studies [6, 7] a specific pattern of
deterioration of AD specific biomarkers has been proposed, which reflects the
underlying progressive neuropathology of the disease. In this model, described
by Jack et al., (2013) concentrations of A* in CSF start decreasing decades
before clinical symptoms appear. Changes in total and phosphorylated tau
(t-Tau, p-Tau) concentrations have been shown to occur in CSF up to 15 years
prior to the clinical onset of AD [8]. As the disease process progresses,
cognitive functions start to decline; at first only noticeable through
sophisticated neuropsychological testing, but eventually also clinically
evident.
Study objective
Main objective of the study is to define an algorithm based on the plasma
biomarkers: A*40, A*42, t-Tau, p-Tau, NfL and APOE * status and NeuroCart
tests, age, grip strength and level of education that distinguishes between
positive and negative A* CSF in healthy elderly.
Study design
Single-centre, observational, correlational study.
Study burden and risks
NA
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Males and females, aged 65 and older (inclusive);
2. Willing and able to perform the cognitive tests, as evidenced by performance on the training session of the cognitive tests;
3. Willing and able to give written informed consent and to comply with the study procedures.
Exclusion criteria
1. Legal incapacity or inability to understand or comply with the requirements of the study;
2. Evidence of cognitive deterioration, as indicated by a diagnosis of a cognitive disorder (including but not limited to MCI, Alzheimer*s disease, Lewy Body Dementia, Fronto-temporal Dementia);
3. History or symptoms of significant psychiatric disease in the past 3 years (including but not limited to clinical depression, schizophrenia);
4. A Mini Mental State Examination (MMSE) score of *24;
5. A Geriatric Depression Scale * 15 (GDS) score of *6;
6. Presence of drug abuse, or positive urine drug screen (UDS) at screening or occasion;
7. Presence of severe alcohol abuse (daily alcohol consumption exceeding 2 standard drinks per day on average for females or exceeding 3 standard drinks per day on average for males (1 standard drink = 10 grams of alcohol)), or a positive breath alcohol test at screening or occasion;
8. Any contradictions for a lumbar puncture as judged by the principal investigator.
9. Any other reason that it is not safe or ethical to allow a subject to participate in the study in the opinion of the investigator.
Design
Recruitment
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 | NL62138.058.17 |