Effect of Supervised Physical Exercise on Brain, Cognition, OMICs, Molecular Markers and Functional Status in Older People at Risk of Mild Cognitive Impairment: Rationale, Design and Methodology.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Mild Cognitive Impairment
- Sponsor
- University of Cadiz
- Enrollment
- 98
- Locations
- 1
- Primary Endpoint
- Assessed changes from Baseline Neuroimaging Markers of Brain Structures (thickness in mm; volumes in mm)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This project aims to examine the effect of a 5-month period supervised exercise intervention on brain, cognition, OMICs, Molecular Markers and functional status in older people at risk of mild cognitive impairment. Secondarily, the effect of this intervention on antioxidant capacity, lipid metabolism and glucose, physical health (functional capacity, blood pressure, body composition) and mental (quality of life and depression) will be studied, as well as other factors risk (genetic and biological) for the development of Alzheimer. A total of 100 people aged between 65 and 75 years old at risk of mild cognitive impairment will be randomly distributed in the supervised exercise intervention group (n = 50) and control group (n = 50). The design will include a 5-month intervention with measurements at pre and post intervention and a third measurement (retest) after 3 months of completion. The multicomponent supervised exercise program will include aerobic, strength, cognitive and coordinative-agility-balance works, and progression will be established in different load parameters (frequency, volume, intensity, density). Therefore, randomized controlled studies are needed to know the specific effect of dose-response considering the various dimensions in parallel such as neuroimaging, cognitive status and OMICS. This will allow us to understand from a comprehensive perspective the causes and mechanisms underlying the response. This project will significantly increase scientific knowledge about the role of exercise on brain as a therapeutic measure in people at risk of mild cognitive impairment from a multidimensional perspective. The project will have a significant impact at social and economic level by transferring the study findings to social and health setting by means of agents and networks provided for the project.
Investigators
David Jimenez Pavon
Ramón y Cajal Senior Researcher
University of Cadiz
Eligibility Criteria
Inclusion Criteria
- •Do not present any physical illness that prevents you from doing physical activity
- •Able to communicate without problems
- •Able to read and understand informed consent as well as the object of the study
Exclusion Criteria
- •Acute or terminal illness
- •Diagnosis of Alzheimer's
- •History of cranioencephalic trauma with loss of consciousness
- •History of cerebral infarction, epilepsy, brain tumor
- •Unstable cardiovascular disease
- •Recent fracture in upper or lower limb
- •Alcohol abuse and / or habitual drug use or drug infusion pump
- •Presence of pacemakers, defibrillator, metallic implants in the head, intraocular and / or maxillo-facial structures, dental prostheses incompatible with magnetic resonance studies
- •Intravascular devices (stent, Coil, filter), heart valve, aneurysm clip, neurostimulator, intravascular catheter with metal or cardiovascular bypass
- •Severe visual or auditory problems, implant in the middle / inner ear
Outcomes
Primary Outcomes
Assessed changes from Baseline Neuroimaging Markers of Brain Structures (thickness in mm; volumes in mm)
Time Frame: up to 24 weeks
Brain magnetic resonance images will be acquired in a Philips-Ingenia 3-Tesla scanner with a 32-channel digital coil exclusively dedicated to skull (Philips, The Netherlands) with the anatomical sequences: 1. Sequence T1-3D in sagittal orientation. This sequence will quantify the cortical thickness and perform morphometric studies of cortical and subcortical structures. The pattern of cortical thickness changes and the volume of different brain structures will be obtained with the tools implemented in the software Freesurfer v5.3 and SPM12.
Assessed changes from Baseline Neuroimaging Markers of Brain Function (level of activity in percentage)
Time Frame: up to 24 weeks
Brain magnetic resonance images will be acquired in a Philips-Ingenia 3-Tesla scanner with a 32-channel digital coil exclusively dedicated to skull (Philips, The Netherlands) with the anatomical sequences: 1. DTI (Diffusion Tensor Imaging) sequence in axial orientation. This sequence will allow to evaluate the properties of the microstructure of the white matter and its nerve fiber tracts. 2. T2 / FLAIR sequences in axial orientation. Both sequences will be used to determine the degree of involvement of the deep and periventricular white matter using the Fazekas scale.
Assessed changes from Baseline Cognitive Status
Time Frame: up to 36 weeks
An overall SCORE (z-score values or similar;higher value for better outcome) of the 8 measurements on cognitive status will be developed to arrive at one reported value: 1. - Clinical Dementia Rating -CDR: This is a valid and reliable instrument for staging dementia. 2. - Mini Mental State Examination to detect cognitive deterioration. 3. - Trail Making Test -TMT: This is an indicator of the speed of cognitive processing and executive functioning. 2 parts. 4. - Boston Naming Test to assess the ability to name objects. 5. - Clock Drawing Test -CDT: valid test for evaluation of cognitive deterioration. 6. - Rey Auditory Verbal Learning Test -RAVLT: learning and verbal episodic memory. 7. - The Stroop Color and Word Test -SCWT: examines basic psychological processes (cognitive flexibility, selective attention, resistance to interference from external stimuli and cognitive inhibition). 8. -Controlled Oral Word Association Test -COWAT: designed to assess verbal fluency.
Assessed changes from Baseline OMICs Analysis
Time Frame: up to 36 weeks
To carry out the analysis of the OMICs a full untargeted profiling will be carried out in the pre and post-intervention and retest measurements for different OMICS including metabolomics, proteomics,etc. For these analyzes, the following large equipment and techniques will be used, ultrahigh performance liquid chromatography / mass spectrometry (LC-quadrupole-time of flight, QTPF-MS, Agilent 1200-Agilent 6520); capillary electrophoresis / mass spectrometry (CE, TOF-MS, Agilent 7100-Agilent 6210) and gas chromatography / mass spectrometry (GC, EI-GC), mass spectrometry (capillary electrophoresis / mass spectrometry, CE-TOF-MS; Q-MS, (Quadrupolo, Agilent 7890A-Agilent 5965C) In addition, data processing platforms will be used, both mass databases and statistical tools for multivariate analysis: Mass Hunter, Mass Profiler Professional, SIMCA, MATLAB.
Assessed changes from Baseline Molecular Makers
Time Frame: up to 36 weeks
The telomere length will be measured by quantitative real-time PCR (RT-qPCR) following the method previusly described. Briefly, the DNA from the cell fraction of the blood will be extracted with the DNeasy Blood \& Tissue Kit (Qiagen) following the manufacturer's specifications. The DNA concentration of the sample, as well as its integrity, will be confirmed in a NanoDrop 2000. For the RT-qPCR the telomeric sequence will be amplified as well as a single copy gene sequence to normalize. Calibration curves will be made with serial dilutions of known concentration of both the gene sequence as well as an oligo specially designed to contain 114 copies of the TTAGGG telomeric sequence. The RT-qPCR will be carried out with 20 ng of DNA using myScript SYBR Green PCR Kit (ROCHE). The PCR conditions are: 10 min at 95 ° C, followed by 40 cycles of 95 ° C for 15 sec and 60 ° C for 1 min, followed by the corresponding dissociation curve.
Secondary Outcomes
- Assessed changes from Baseline Physical Health of hemodynamic status(up to 36 weeks)
- Assessed changes from Baseline Physical Health Parameters on Functional capacity: Muscle-skeletal(up to 36 weeks)
- Assessed changes from Baseline Physical Health Parameters on Functional capacity: Cardiorespiratory fitness(up to 36 weeks)
- Assessed changes from Baseline Physical Health Parameters on Functional capacity:Agility-motor coordination(up to 36 weeks)
- Assessed changes from Baseline Physical Health Parameters on Functional capacity: Flexibility(up to 36 weeks)
- Assessed changes from Baseline Physical Health Parameters on Functional capacity: Handgrip strength(up to 36 weeks)
- Assessed changes from Baseline Incremental Exercise test:(up to 36 weeks)
- Assessed changes from Baseline Physical Health by the Scale of instrumental activities of the daily life of Lawton and Brody(up to 36 weeks)
- Assessed changes from Baseline Physical Health of Body Composition: Weight(up to 36 weeks)
- Assessed changes from Baseline Physical Health of Body Composition:Height(up to 36 weeks)
- Assessed changes from Baseline Physical Health of Body Composition: Waist Circumference(up to 36 weeks)
- Assessed changes from Baseline Physical Health of Body Composition: Body mass index(up to 36 weeks)
- Assessed changes from Baseline Physical Health of Body Composition: Total body fluids(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile: Glucose.(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile:Total cholesterol(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile:HDL cholesterol(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile: LDL Cholesterol(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile:triglycerides(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile:Apolipoprotein B(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile:Insulin(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Cardio-metabolic Risk Factors Profile: HOMA(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Antioxidant Capacity(up to 36 weeks)
- Assessed changes from Baseline Blood Sample of the Neurotrophic Factor Derived from the Brain (neurotransmitter)(up to 36 weeks)
- Assessed of Baseline levels for Cerebrospinal fluid:(baseline)
- Assessed changes from Baseline Quality of life as assessed through the quality of life questionnaire related to health (Short-Form Health Survey 36 -SF36)(up to 36 weeks)
- Assessed changes from Baseline of Depression using the Geriatric Depression Scale (GDS)(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics: Age.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics.Sex.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics.Marital Status.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics.Educational level and socio-economic status.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics.Family history of dementia.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics.Medication.(up to 36 weeks)
- Assessed changes from Baseline of Sociodemographic Characteristics. Other pathologies.(up to 36 weeks)