Concentration of Trimethylamine Oxide (TMAO) in Blood Plasma as a Risk Factor for Vascular Cerebral Damage

Study Overview
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Brief Summary
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The primary aim of the current research project is to answer the question, whether plasma trimethylamine N-oxide (TMAO) level may be used as a marker of ischemic changes in the brain. TMAO is associated with endothelial dysfunction, inflammation and oxidative stress. The hypothesis is that circulating TMAO level may predict leukoaraiosis (LA) and/or stroke. Secondary, the investigators would like to examine whether plasma TMAO concentration is related to cognitive impairment and determine whether choline consumption is associated with an incidence of LA severity and dementia.

Detailed Description
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In the study, subjects will be recruited in the hospital among the patients with brain MRI performed within past 4 weeks. All MRI scans will be reviewed by the neurologist to evaluate ischemic changes. Upon detection of LA, patients (n=150) will be informed about the study aims. In the same time, aged- and sex-matched control group (n=150) with no detected ischemic changes will be recruited. In each group, the blood samples will be collected, to determine the concentration of plasma TMAO, oxidative stress markers, as well as serum endothelial dysfunction markers and biochemical parameters. To determine the cognitive performance psychological test will be carried out. The diet of all recruited participants, with special consideration on the choline-rich products and supplements, will be analyzed.

Official Title
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Concentration of Trimethylamine Oxide (TMAO) in Blood Plasma as a Risk Factor for Vascular Cerebral Damage

Conditions
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Vascular Diseases, Leukoaraiosis, Ischemia, Cerebral

Intervention / Treatment
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* Diagnostic Test: Magnetic Resonance Imaging (MRI)
* Diagnostic Test: Blood samples collection
* Diagnostic Test: Neuropsychological tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: the ischemic changes in the brain (diagnosed by neurologist by MRI scans) Exclusion Criteria: no ischemic changes in the brain (diagnosed by neurologist by MRI scans)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ischemic changes<br>Patients with ischemic changes in the brain diagnosed by MRI | Diagnostic Test: Magnetic Resonance Imaging (MRI)<br>* Magnetic Resonance Imaging (MRI) to diagnose ischemic changes in the brain.<br>Diagnostic Test: Blood samples collection<br>* Trimethylamine N-oxide (TMAO) concentration, oxidative stress markers and endothelial dysfunction markers will be determined in blood samples.<br>Diagnostic Test: Neuropsychological tests<br>* Cognitive functions assessment<br>|
| No ischemic changes<br>Patients without ischemic changes in the brain diagnosed by MRI | Diagnostic Test: Magnetic Resonance Imaging (MRI)<br>* Magnetic Resonance Imaging (MRI) to diagnose ischemic changes in the brain.<br>Diagnostic Test: Blood samples collection<br>* Trimethylamine N-oxide (TMAO) concentration, oxidative stress markers and endothelial dysfunction markers will be determined in blood samples.<br>Diagnostic Test: Neuropsychological tests<br>* Cognitive functions assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Magnetic Resonance Imaging (MRI) | Leukoaraiosis severity will be evaluated in MRI scans according to the Fazekas' scale. Will be grading scale for periventricular hyperintensities (PVH) and scale of deep white matter hyperintensities. | before qualifying for the study, during the recruitment period | 
| Trimethylamine-N-oxide (TMAO) blood concentration | TMAO concentration determined by the ultra-performance liquid-chromatography tandem mass spectrometry (UPLC-MS/MS), marked in µmol/l. | up to 4 weeks after brain MRI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain-derived neurotrophic factor (BDNF) | BDNF concentration determined in serum by ELISA method, marked in pg/mg. | up to 4 weeks after brain MRI | 
| Mini Mental State Examination (MMSE) | MMSE is a screening tool for cognitive functions impairment. | up to 4 weeks after brain MRI | 
| Trail Making Test (TMT) | TMT test to determine the executive functions. | up to 4 weeks after brain MRI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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trimethylamine-N-oxide, magnetic resonance imaging, cognitive functions