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

Not Applicable

• Conditions: Cognitive Impairment; Motoric Cognitive Risk Syndrome
• Interventions: Behavioral: Physical exercise (PE); Other: Control; Device: Transcranial current stimulation (tCS)

• Registration Number: NCT04115215
• Lead Sponsor: Parc Sanitari Pere Virgili

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-30
• Study First Submitted QC: 2019-10-02
• Study First Posted: 2019-10-03
• Study Start: 2020-03-23
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-30
• Last Update Posted: 2021-07-02
• Primary Completion: 2023-03-23
• Study Completion: 2023-03-23

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 93

Inclusion Criteria

1. older adults (65 years or older)
2. with Motoric Cognitive Risk Syndrome
3. 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)
4. mobility impairment (measured as slow gait speed<0.8 m/s)
5. without diagnosed clinical neurological or psychiatric diseases
6. with a preserved functional status for the activities of daily living
7. who can walk without help from third parties

Exclusion Criteria

1. a diagnosis of dementia
2. advanced/terminal disease (life expectancy<1 year)
3. contraindications to exercise and tCS
4. unwilling to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	Physical exercise (PE)	Physical exercise (PE)
Arm 2	Physical exercise (PE)	Transcranial current stimulation (tCS)
Arm 2	Transcranial current stimulation (tCS)	Transcranial current stimulation (tCS)
Control	Control	Educational sessions on healthy aging

Primary Outcome Measures

Name	Time	Method
Changes in hemoglobin oxygenation during functional tasks, as measured using fNIRS+fDCS optical techniques.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	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.

Secondary Outcome Measures

Name	Time	Method
Cognitive executive function tests - Phonetic Verbal Fluency	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	Phonetic verbal fluency will be measured by scoring total number of words (not repeated) per unit of time, with higher rates revealing better performance.
Physical function	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	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.
Motor function	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	"Dual task" measure: cost of gait speed reduction when a cognitive task (verbal fluency) is associated during gait, compared to gait alone.
Rey Auditory Verbal Learning Test (RAVLT)	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	Rey Auditory Verbal Learning Test (RAVLT) is a validated neuropsychological test used to assess verbal memory function.
Cognitive executive function tests - SDMT	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	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.
Cognitive executive function tests - Digit span	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	The digit span is a widely used neuropsychological test to assess attention and working memory.
Cognitive executive function tests - Trail Making Test	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.	Trail Making Test (TMT A and B) will be perform to assess executive function (attention).

Trial Locations

Locations (5)

Parc Sanitari Pere Virgili; 🇪🇸 Barcelona, Spain

Fundació Ictus; 🇪🇸 Barcelona, Spain

Hospital Universitario La Ribera; 🇪🇸 Alzira, Valencia, Spain

Institut Català de la Salut; 🇪🇸 Barcelona, Spain

The Institute of Photonic Sciences (ICFO); 🇪🇸 Castelldefels, Barcelona, Spain