Breathing, Relaxation, Attention Training, & Health in Older Adults (BREATHE)

NCT ID: NCT04522791

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-18
• Study Completion Date: 2026-02-28

Brief Summary

A recently completed study suggested that processing speed and attention (PS/A) oriented cognitive training (VSOP) produced robust effect on PS/A and working memory, but not in cognitive control or episodic memory, and long-term effects were overall modest. The proposed R01 renewal proposes to identify additional attributes to further enhance transferred and long-term effects of PS/A training in older adults with amnestic mild cognitive impairment (MCI) by addressing adaptation capacity that underpins adaptive learning and neuroplasticity. The goal of the stage II double-blinded randomized trial is to test whether adding resonance frequency breathing (RFB) training to VSOP will strengthen multiple contributors to adaptation capacity, particularly the central and peripheral pathways of autonomic nervous system (ANS) flexibility, which will strengthen VSOP training effect on cognitive and brain function and slow the progress of dementia in MCI. The central hypothesis is that strengthening adaptation capacity, via improving autonomic nervous system (ANS) flexibility, will enhance neuroplasticity and slow progress of dementia in MCI, since adaptation capacity is critical for neuroplasticity of VSOP, but compromised in neurodegenerative process. Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a waitlist IR control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility and multiple markers of dementia progress. Data will be collected across a 14-month period. The two primary aims are to examine long-term effects of the combined intervention on ANS flexibility (Aim 1), as well as the cognitive, behavioral, and functional capacity (Aim 2). The exploratory aim will be to determine the preliminary long-term effect of the combined intervention on neurodegeneration. This can be a reasonable renewal plan from the completed study, aiming to identify additional attributes to further enhance transferred and long-term effects of cognitive training in MCI. This will be among the first randomized controlled trials to examine a novel, combined intervention targeting adaptation capacity in MCI, with an ultimate goal for slowing neurodegeneration.

In addition, research on how to monitor adherence - the extent to which VSOP training is delivered and followed as intended - has been conceptually and methodologically limited. Robust monitoring of adherence to cognitive training requires valid assessment of effective engagement. Here, we apply our well-supported, novel framework of mental fatigability for measuring effective engagement in cognitive training. Mental fatigability, the failure to remain engaged in tasks requiring sustained mental effort, can be captured via measures of self-reported disengagement, increase in reaction time during tasks, and facial expression of negative valence/low arousal. These markers of disengagement relate to ventromedial prefrontal cortex dysfunction. We will apply this framework to advance understanding of the underpinnings of adherence to VSOP training by monitoring the extent of effective engagement while using the training platform.

Conditions

Mild Cognitive Impairment; Healthy Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

RFB+VSOP (MCI)

For home-based RFB+VSOP: The investigators will instruct subjects to do 10-minutes of app- guided paced breathing at RF daily; for select days, there will be VSOP training immediately following RFB.

A total of 8 weeks intervention. The investigators will extend the intervention for additional two weeks for make-up sessions.

Group Type: EXPERIMENTAL

RFB

Intervention Type: BEHAVIORAL

The RFB protocol entails a combination of 8 weekly, in-lab training sessions using HRV biofeedback software (Physiocom, Seattle, WA) and daily paced breathing homework using a mobile-based HRV biofeedback app (Inner Balance, HeartMath, LLC, CA).

VSOP

Intervention Type: BEHAVIORAL

The investigators will use the INSIGHT online program (Posit Science). The platform will be built for our study, including 5 tasks (Eye for detail, Peripheral challenge, Visual sweep, Double decision, Target tracker) that practice different cognitive processes with PS/A as the shared domain.

IR+VSOP (MCI)

The control IR strategy will be used, set-up of which will be the same as the RFB + VSOP intervention group with IR replacing RFB. A total of 8 weeks intervention. The investigators will extend the intervention for additional two weeks for make-up sessions.

Group Type: ACTIVE_COMPARATOR

VSOP

Intervention Type: BEHAVIORAL

The investigators will use the INSIGHT online program (Posit Science). The platform will be built for our study, including 5 tasks (Eye for detail, Peripheral challenge, Visual sweep, Double decision, Target tracker) that practice different cognitive processes with PS/A as the shared domain.

IR

Intervention Type: BEHAVIORAL

Guided imagery relaxation, equal in dose and frequency to RF practice, will be used to control for relaxation effects that may occur via RFB (which could provide an alternative explanation for outcomes). IR activities will be facilitated using the Insight Timer mobile-based app, which emphasizes the use of visualization and imagery strategies to help the body relax.

IR only (MCI)

Participants randomized to this condition will receive weekly in-person check-in visits, and perform daily 10-minute IR, so that the number of treatment contacts (though not duration) will be equivalent. A total of 8 weeks intervention. The investigators will extend the intervention for additional two weeks for make-up sessions.

Group Type: PLACEBO_COMPARATOR

IR

Intervention Type: BEHAVIORAL

Guided imagery relaxation, equal in dose and frequency to RF practice, will be used to control for relaxation effects that may occur via RFB (which could provide an alternative explanation for outcomes). IR activities will be facilitated using the Insight Timer mobile-based app, which emphasizes the use of visualization and imagery strategies to help the body relax.

RFB+VSOP (HC)

this is a new healthy control intervention arm used for testing adherence related items.

For home-based RFB+VSOP: The investigators will instruct subjects to do 10-minutes of app- guided paced breathing at RF daily; for select days, there will be VSOP training immediately following RFB.

A total of 8 weeks intervention. The investigators will extend the intervention for additional two weeks for make-up sessions.

Group Type: OTHER

RFB

Intervention Type: BEHAVIORAL

The RFB protocol entails a combination of 8 weekly, in-lab training sessions using HRV biofeedback software (Physiocom, Seattle, WA) and daily paced breathing homework using a mobile-based HRV biofeedback app (Inner Balance, HeartMath, LLC, CA).

VSOP

Intervention Type: BEHAVIORAL

The investigators will use the INSIGHT online program (Posit Science). The platform will be built for our study, including 5 tasks (Eye for detail, Peripheral challenge, Visual sweep, Double decision, Target tracker) that practice different cognitive processes with PS/A as the shared domain.

Interventions

RFB

The RFB protocol entails a combination of 8 weekly, in-lab training sessions using HRV biofeedback software (Physiocom, Seattle, WA) and daily paced breathing homework using a mobile-based HRV biofeedback app (Inner Balance, HeartMath, LLC, CA).

Intervention Type: BEHAVIORAL

VSOP

The investigators will use the INSIGHT online program (Posit Science). The platform will be built for our study, including 5 tasks (Eye for detail, Peripheral challenge, Visual sweep, Double decision, Target tracker) that practice different cognitive processes with PS/A as the shared domain.

Intervention Type: BEHAVIORAL

IR

Guided imagery relaxation, equal in dose and frequency to RF practice, will be used to control for relaxation effects that may occur via RFB (which could provide an alternative explanation for outcomes). IR activities will be facilitated using the Insight Timer mobile-based app, which emphasizes the use of visualization and imagery strategies to help the body relax.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. All participants will require a diagnosis of "mild cognitive impairment due to Alzheimer's disease"using the most recent NIA and Alzheimer's Association workshop criteria:

1. Presence of memory complaint,

2. Rey Auditory Verbal Learning Test delayed recall (for memory) < 6,

3. Montreal Cognitive Assessment (for global cognition) ranged 18 and 25,

4. Activities of Daily Living Questionnaire ≤ 30,

2. Intact score for San Diego Brief Assessment of Capacity to Consent (UBACC).

3. If a participant is on Alzheimer's disease medication (i.e., memantine or cholinesterase inhibitors), antidepressants, anxiolytics, or vascular risk or diseases related medications (e.g., beta- blocker), the dose should be stable for 3 months prior to recruitment.

4. Age 60-89,

5. English-speaking,

6. Adequate visual and hearing acuity for using mobile-based apps and testing by self-report, and

7. Community-dwelling.

Exclusion Criteria

1. Current enrollment in another cognitive improvement study;

2. Uncontrollable symptoms of major depression;

3. Major cerebrovascular and cardiovascular diseases (e.g., congestive heart failure, pacemaker, prior myocardial infarction);

4. Neurological diseases (e.g., Parkinson's disease, Multiple Sclerosis);

5. Having an active legal guardian (indicating impaired capacity for decision making);

6. MRI contraindication (e.g., pacemaker, claustrophobia).

7. Color blindedness

8. Alcohol dependency in the past 5 years that are the main contributor to MCI

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: collaborator

National Institute of Nursing Research (NINR)

NIH

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Kathi Heffner

Associate Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Feng Lin

Rochester, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Feng Lin, PhD

Role: CONTACT

vankee_lin@urmc.rochester.edu

15852766002

Kathi Heffner, PhD

Role: CONTACT

kathi_heffner@urmc.rochester.edu

15852766002

Facility Contacts

Feng Lin

Role: primary

vankee_lin@stanford.edu

5852766002

References

Lin FV, Heffner K, Gevirtz R, Zhang Z, Tadin D, Porsteinsson A. Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial. Trials. 2021 Aug 23;22(1):560. doi: 10.1186/s13063-021-05530-z.

Reference Type: DERIVED

PMID: 34425878 (View on PubMed)

Other Identifiers

R01NR015452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00004727

Identifier Type: -

Identifier Source: org_study_id