The main objective of this study is to find (epi)genetic markers including SNPs/haplotypes, DNA methylation and RNA expression correlating with cognitive decline in clinical patients with Mild Cognitive Impairment (MCI) and Subjective Cognitive…
ID
Source
Brief title
Condition
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is memory decline on the Verbal Learning Test
(VLT). Genetic markers will include DNA and RNA (expression).
Secondary outcome
The outcome of the other cognitive tests will be analysed as secondary outcome
measures.
Background summary
In Alzheimer*s disease (AD), individual disease risk is determined by genetic,
environmental, and demographic factors, as well as interactions between them.
Epigenetic mechanisms, such as DNA methylation, represent critical risk factors
in AD pathogenesis and related cognitive dysfunction (Lardenoije et al., 2015).
Thus, understanding the precise, possibly intricate role of genetic and
epigenetic mechanisms in the pathogenesis of AD and its contribution to
susceptibility will increase our knowledge of AD and will in turn be of pivotal
importance for development of novel therapeutic hypotheses.
Study objective
The main objective of this study is to find (epi)genetic markers including
SNPs/haplotypes, DNA methylation and RNA expression correlating with cognitive
decline in clinical patients with Mild Cognitive Impairment (MCI) and
Subjective Cognitive Decline (SCD) from a memory clinic setting.
Study design
A prospective cohort study in which patients from the Maastricht Memory clinic
are followed every six months for the period of two years. The present proposal
is one of the two arms of the *Cognition and (epi)genetics study*. During
baseline and the follow-up assessments, patients undergo a cognitive
testbattery. The genomics (RNA) and genetics (DNA) parameters obtained from
blood samples will be linked to cognitive performances.
Study burden and risks
This study involves no or minimal risks for the subjects. At baseline, clinical
data, and blood samples are collected as part of clinical routine. At baseline,
this project does not require additional questionnaires or neuropsychological
testing besides clinical routine. Only an extra amount of maximal 18 mL blood
is collected of patients who already undergo a venepuncture for clinical
purposes. At follow-up measurements, a short neuropsychological assessment
(including the VLT) will be performed and a venepuncture for the collection of
18 mL blood.
One Takeda Parkway 00 00
IL-Deerfield 60015
US
One Takeda Parkway 00 00
IL-Deerfield 60015
US
Listed location countries
Age
Inclusion criteria
MCI patients
1) Referred to the memory clinic for the evaluation of cognitive problems, and
2) Patients have to fulfil the new DSM-V criteria for mild neurocognitive disorder (NCD):
a) Evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains, being between 1-2 standard deviations (SD) below average. The evidence should consist of concern of the individual, a knowledgeable informant, or the clinician that there's been a mild decline in cognitive functioning; and a modest impairment in cognitive performance, documented by standardized neuropsychological testing.
b) The cognitive deficits do not interfere with capacity for independence in everyday activities.
c) The cognitive deficits don't occur exclusively in context of delirium, and are not better explained by another mental disorder.
These inclusion criteria, and collection of clinical data, will allow use of different internationally used MCI criteria.;SCD patients (based on Jessen et al., Alz Dem, 2014)
1) Also being referred for the evaluation of cognitive complaints;
2) Self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event; and
3) Normal age-, gender-, and education- adjusted performance on standardized cognitive tests.
SCD might be a very early symptom of neurodegenerative brain processes, and are therefore interesting for evaluation in the present study.
Exclusion criteria
Exclusion criteria for both groups of patients are: having received chemo treatment in the past year, Normal Pressure Hydrocephalus, Morbus Huntington, Parkinson's Disease, recent Transient Ischemic Attack (TIA) or Cerebrovascular Accident (CVA) (< 2 years), TIA/CVA followed by cognitive decline (within three months), history of schizophrenia, bipolar disorder or psychotic symptoms not otherwise specified or previous treatment for these diseases (ever), current major depressive disorder, cognitive problems due to alcohol abuse, brain tumor, epilepsy, encephalitis, mental incompetence for deciding participation (also when patient develop mental incompetence during the study, they will be excluded for follow-up assessments), or patients with the expectation that a follow-up assessment after one year will not be possible. During the period of the present study, patients are not allowed to participate in other drug trials; other treatments or interventions are no exclusion criteria.
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 | NL55925.068.16 |