Pre-FRONTal Brain STability, Key for Action Against Disability in AGing

Study Overview
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Brief Summary
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Cognitive and mobility impairments are critical contributors to dementia and disability in older adults, and can be caused by neurodegenerative and neurovascular changes at the pre-frontal (PF) brain areas. In a previous technological project funded by ISCiii, the investigators adapted a non-invasive, point-of-care optical methods (fNRIS/fDCS technology) to study PF metabolism and blood flow activation during cognitive and motor tasks, in older adults with and without cognitive impairment. These methods are sensitive to change after physical exercise (PE) and after selectively and safely stimulating PF areas with electrical transcranial direct current stimulation (tCS). PE and tCS have shown benefits for cognition and mobility in the elderly, but their prolonged effect on PF hemodynamic activation has not been studied. Understanding the specific action of these interventions on the brain, and their clinical cognitive and motor impact, is key to fine-tune appropriate treatment strategies. The FRONT STAGE project aims to compare, through a 3 arms single-blind randomized clinical trial, the impact of a 10 weeks, 1 hour/week program of PE (arm 1) Vs PE+tCS (arm 2) and Vs a control group (arm 3, healthy aging sessions and control of cardiovascular risk factors). The PE program is already implemented in primary care, as part of another previous project of the investigators' research group. Outcomes will include the optical measurement of PF metabolism and blood flow and clinical measures of cognitive and physical function. Front STAGE project will recruit 93 older adults with cognitive impairment and slow gait, but without dementia or disability in the activities of daily living (N=31 per arm). They will receive a comprehensive geriatric assessment at baseline, together with the optical, cognitive and physical measures, and will be follow-up at 3 and 6 months. Weekly physical activity through accelerometry will be controlled in analyses. FRONT STAGE project centered on aging and the prevention of dementia and disability, will provide, translationally, more evidence to support and enlarge the clinical application of these interventions, and will contribute to foster further research in this field.

Official Title
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Pre-FRONTal Brain STability, Key for Action Against Disability in AGing: The FRONT STAGE Project

Conditions
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Cognitive Impairment, Motoric Cognitive Risk Syndrome

Intervention / Treatment
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* Behavioral: Physical exercise (PE)
* Device: Transcranial current stimulation (tCS)
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: older adults (65 years or older) with Motoric Cognitive Risk Syndrome characterized by impaired cognition (which in our case will be confirmed with a Spanish version of the Montreal cognitive Assessment (MOCA), score between 26 and 21) mobility impairment (measured as slow gait speed<0.8 m/s) without diagnosed clinical neurological or psychiatric diseases with a preserved functional status for the activities of daily living who can walk without help from third parties Exclusion Criteria: a diagnosis of dementia advanced/terminal disease (life expectancy<1 year) contraindications to exercise and tCS unwilling to give informed consent

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Physical exercise (PE) | Behavioral: Physical exercise (PE)<br>* This arm includes 10 sessions of multi-component exercise sessions (including aerobic, resistance, flexibility, dual-tasking) of 1 hour/week of functional group exercise, directed to foster empowerment for subsequent continuation of exercise in community-dwelling older adults referred by primary care to a geriatrician and an expert physical therapist. Participants will receive a leaflet with instructions to perform five strength-based exercises and instructors will recommend participants to perform the exercises and walk at least 15 minutes daily.<br>|
| Experimental: Arm 2<br>Transcranial current stimulation (tCS) | Behavioral: Physical exercise (PE)<br>* This arm includes 10 sessions of multi-component exercise sessions (including aerobic, resistance, flexibility, dual-tasking) of 1 hour/week of functional group exercise, directed to foster empowerment for subsequent continuation of exercise in community-dwelling older adults referred by primary care to a geriatrician and an expert physical therapist. Participants will receive a leaflet with instructions to perform five strength-based exercises and instructors will recommend participants to perform the exercises and walk at least 15 minutes daily.<br>Device: Transcranial current stimulation (tCS)<br>* This arm includes 1 application/week for 10 weeks during PE, through an adapted commercial helmet. Transcranial current stimulation (tCS) is a neural stimulation technique based on electrical stimulation of selected parts of the brain with direct or alternated electrical current (tDCS or tACS) of very low intensity of 1,5 milliamps (mA), using one or more electrodes placed on the skull. tCS is non-invasive (no surgical procedures) and it is painless, as applied in the proposed protocols.<br>|
| Active Comparator: Control<br>Educational sessions on healthy aging | Other: Control<br>* Participants of similar profile, randomized to the control group, will undergo weekly 30 minutes educational sessions on healthy aging, including relevant aspects of nutrition, self-care, physical activity, plus measurement of blood pressure, heart rate and peripheral oxygen Hb saturation. These participants will be offered to join the PE program after the 6-months follow-up (end of the study).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hemoglobin oxygenation during functional tasks, as measured using fNIRS+fDCS optical techniques. | Our primary outcome will be prefrontal hemoglobin oxygenation during a) cognitive tests, such as phonetic verbal fluency and calculations (2-forward and 3-backward counting), b) normal gait, c) dual task (walking while counting). All the measures will be controlled for extra-cerebral and systemic contributions due to variations in heart-rate, oxygen saturation, respiration rate and end-tidal carbondioxide. Various measures such as those derived from accelerometers to account for potential motion artifacts will be also utilized, followed by a multi-subject analysis. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive executive function tests - Phonetic Verbal Fluency | Phonetic verbal fluency will be measured by scoring total number of words (not repeated) per unit of time, with higher rates revealing better performance. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Rey Auditory Verbal Learning Test (RAVLT) | Rey Auditory Verbal Learning Test (RAVLT) is a validated neuropsychological test used to assess verbal memory function. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Cognitive executive function tests - SDMT | The symbol-digit modalities test (SDMT) is a symbol substitution neuropsychological test that examines a person's attention and speed of processing. Higher scores will indicate better performance. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Physical function | The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance), aggregated from the different subtests. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Motor function | Dual task measure: cost of gait speed reduction when a cognitive task (verbal fluency) is associated during gait, compared to gait alone. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Cognitive executive function tests - Digit span | The digit span is a widely used neuropsychological test to assess attention and working memory. | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 
| Cognitive executive function tests - Trail Making Test | Trail Making Test (TMT A and B) will be perform to assess executive function (attention). | Baseline (prior to intervention), 3 and 6 months after completion of the intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Older adults, Cognitive impairment, Motoric Cognitive Risk Syndrome, Physical disfunction, Multi-component physical exercise program, Transcranial electrical stimulation