Biomarkers of Cognitive Impairment in Blood Cells

Study Overview
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Brief Summary
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The aim of this study is to identify transcriptomic biomarkers in blood cells to diagnose early cognitive impairment. This would allow preventing the development of severe pathologies, such as Alzheimer Disease. In addition, this project will analyse the influence of adiposity, obesity, nutritional habits and physical activity on cognition.

Detailed Description
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Blood cells constitute a minimally invasive material, which is presented as potentially suitable for addressing the identification of clinical diagnostic biomarkers. This study will compare gene expression in blood cells of patients with various degrees of cognitive alteration (mild cognitive impairment due to Alzheimer's disease and dementia due to Alzheimer's Disease) compared to control individuals, to identify early biomarkers of impaired cognition. The availability of non-invasive early biomarkers of cognitive dysfunction is highly relevant in the field of public health, from the point of view of being able to prevent or delay the onset and/or progression of dementia and other cognitive disorders. In addition, it is intended to establish the association between the biomarkers identified with nutritional imbalances and increased adiposity/obesity.

Official Title
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Use of Human Blood Cells for the Identification of Early Biomarkers of Cognitive Damage

Conditions
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Mild Cognitive Impairment Due to Alzheimer's Disease, Dementia Due to Alzheimer's Disease (Disorder)

Intervention / Treatment
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* Other: No intervention will be performed.


Participation Criteria
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Eligibility Criteria
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Control group Inclusion criteria: Age between 55-80 years Absence of cognitive symptoms Normal neuropsychological examination, (Clinical Dementia Rating, CDR = 0) Exclusion criteria: Any disease that could influence their cognitive performance or blood cell parameters. Group with Mild Cognitive Impairment Due to Alzheimer's Disease (MCI group) Inclusion criteria: Age between 55-80 years Established diagnosis of MCI Cognitive deficit of 1.5 standard deviation in at least one of the neuropsychological tests performed, with no relevant functional repercussion (Functional Activities Questionnaire, FAQ<7 and CDR≤0.5) Group with Dementia Due to Alzheimer Disease (AD) Inclusion criteria: Age between 55-80 years Established diagnosis of Alzheimer's disease CDR ≥ 0.5 and positive AD markers in cerebrospinal fluid

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 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 |
| --- | --- |
| Control<br>20 individuals with no cognitive alterations or any other pathology which could alter cognitive performance or blood cells | Other: No intervention will be performed.<br>* No intervention will be performed.<br>|
| Mild Cognitive Impairment Due to Alzheimer's Disease: MCI group<br>20 individuals diagnosed with Mild Cognitive Impairment Due to Alzheimer's Disease with positive AD markers in cerebrospinal fluid | Other: No intervention will be performed.<br>* No intervention will be performed.<br>|
| Dementia due to Alzheimer Disease: AD group<br>20 individuals diagnosed with Dementia Due to Alzheimer Disease with positive AD markers in cerebrospinal fluid | Other: No intervention will be performed.<br>* No intervention will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of semiquantitative gene expression of blood cells between the three groups | Gene expression analysis performed by real-time quantitative polymerase chain reaction (RT-qPCR). Percentage of semiquantitative gene expression between the groups: MCI vs Control, AD vs Control, and MCI vs AD | Baseline point (all groups) | 
| Mini-Mental State Examination (MMSE), questionnaire (numerical scale) | Cognitive test | Baseline point (all groups) | 
| Montreal Cognitive Assessment (MoCA), questionnaire (numerical scale) | Cognitive test | Baseline point (all groups) | 
| Cognitive Reserve Questionnaire (CRIq), questionnaire (numerical scale) | Cognitive test | Baseline point (all groups) | 
| Body composition (fat mass) | Percentage of fat mass measured using a dual energy x-ray absorptiometry (DXA) scanner | Baseline point (all groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height (cm) | Basic anthropometric parameter, measured in centimeters with a tape-measure | Baseline point (all groups) | 
| Weight (kg) | Basic anthropometric parameter, measured using a scale | Baseline point (all groups) | 
| Waist-hip ratio (numerical ratio) | Basic anthropometric parameter. Waist circumference (cm) and hip circumference (cm) will be combined to report waist-hip ratio (waist(cm)/hip(cm)) | Baseline point (all groups) | 
| Blood pressure (mm Hg) | Basic anthropometric parameter, measured in millimeters of mercury with a blood pressure monitor | Baseline point (all groups) | 
| Body Mass Index (BMI) (kg/m2) | Basic anthropometric parameter. Weight and height will be combined to report BMI in kg/m^2 | Baseline point (all groups) | 
| Complete blood count test (numbers of cells/mcL) | Circulating parameter (from blood sample). It will be measured: red blood cells, white blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils) and platelets. All of them measured in numbers of cells/mcL by a complete blood count test. | Baseline point (all groups) | 
| Plasma glucose (mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Triglycerides (TG, mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Total cholesterol (mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| High-density lipoprotein cholesterol (HDL-C,mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Low-density lipoprotein cholesterol (LDL-C, mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Aspartate aminotransferase (AST, U/L) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Alanine aminotransferase (ALT, U/L) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Gamma-glutamyl transpeptidase (GGT, U/L) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Transpeptidase (GGT, U/L) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| C-reactive protein (CRP, mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Apolipoprotein E (APOE, mg/dL) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Glycated hemoglobin (HbA1c, %) | Circulating parameter (from blood sample) | Baseline point (all groups) | 
| Test on nutritional habits, questionnaire (numerical scale) | Lifestyle test. Test on nutritional habits based on a 14-item Mediterranean diet questionnaire | Baseline point (all groups) | 
| International Physical Activity Questionnaire, IPAQ (numerical scale) | Lifestyle test, specifically a physical activity test | Baseline point (all groups) | 
| STOP-BANG Sleep Apnea Questionnaire (numerical scale) | Lifestyle test, specifically a screening for obstructive sleep apnea in adults | Baseline point (all groups) | 
| Gait Speed Test (m/s) | Gait speed is recorded on a 4 meter walkway with 2 meter non-instrumented walkway segments at each end to allow for acceleration and deceleration. Gait speed recorded is the average of the speed for the two trials | Baseline point (all groups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild Cognitive Impairment, Alzheimer Disease, Blood cells, Adiposity, Nutrition