Breathing Training for Cognitive Impairment

Overseen By Feng Lin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Major depression, Cardiovascular diseases, Neurological diseases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

114 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that if you are on Alzheimer's disease medication, antidepressants, anxiolytics, or medications for vascular risk or diseases, your dose should be stable for 3 months before joining. You don't need to stop these medications, but you should not change the dose during this period.

What data supports the effectiveness of the treatment Breathing Training for Cognitive Impairment?

Research shows that slow and deep breathing techniques can improve heart rate variability, mood, and cognitive functions like memory and attention. These techniques have been beneficial in both elderly populations and young adults, suggesting they may help with cognitive impairment. ^{1 2 3 4 5}

Is breathing training safe for humans?

Research on slow breathing techniques, including resonance frequency breathing, shows they are generally safe for humans. These techniques can improve heart rate variability, reduce blood pressure, and enhance mood without significant adverse effects. ^{1 3 6 7 8}

How does the treatment RFB, VSOP differ from other treatments for cognitive impairment?

This treatment is unique because it uses slow and deep breathing techniques to enhance brain function and mood by increasing heart rate variability and altering brain activity, which is different from traditional drug-based approaches. ^{1 2 3 9 10}

Eligibility Criteria

This trial is for older adults aged 60-89 with mild cognitive impairment due to Alzheimer's, who score within a specific range on cognitive assessments and can handle daily activities. They must be stable on certain medications if taken, speak English, have good vision and hearing for app use, and not have major cardiovascular diseases or other disqualifying conditions.

Inclusion Criteria

I am between 60 and 89 years old.

I live in my own home or with family.

English-speaking,

Exclusion Criteria

Current enrollment in another cognitive improvement study;

You have difficulty distinguishing colors.

You have had a problem with alcohol abuse that has affected your ability to think clearly within the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an 8-week combined intervention of RFB+VSOP or control interventions with periodical booster training sessions

8 weeks

Weekly in-person check-in visits

Follow-up

Participants are monitored for long-term effects on ANS flexibility and cognitive function

14 months

Booster Sessions

Periodical booster training sessions to reinforce treatment effects

Throughout follow-up period

Treatment Details

Interventions

• IR
• RFB
• VSOP

Trial Overview The study tests whether adding resonance frequency breathing (RFB) to processing speed/attention training (VSOP) enhances brain function in those with mild cognitive impairment. Participants are randomly assigned to combined RFB+VSOP intervention, VSOP with relaxation control, or waitlisted. The goal is to improve autonomic nervous system flexibility and slow dementia progression.

Participant Groups

Group I: RFB+VSOP (MCI) Experimental Treatment 2 Interventions

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 II: RFB+VSOP (HC) Experimental Treatment 2 Interventions

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 III: IR+VSOP (MCI) Active Control 2 Interventions

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 IV: IR only (MCI) Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

National Institute of Nursing Research (NINR)

Collaborator

Trials

623

Recruited

10,400,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Findings from Research

Slow breathing techniques (less than 10 breaths per minute) significantly enhance autonomic and central nervous system activities, leading to increased heart rate variability and changes in brain activity, as evidenced by EEG and fMRI studies.

These techniques are associated with improved psychological outcomes, such as increased relaxation and reduced anxiety and depression, suggesting that slow breathing can promote overall emotional well-being in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing. Zaccaro, A., Piarulli, A., Laurino, M., et al.[2020]

Deep and slow breathing (DSB) significantly improved cognitive functions such as retention, attention, working memory, and spatial perception in elderly subjects, suggesting its potential as a dementia prevention strategy.

The study involved 45 elderly participants divided into three groups, with cognitive abilities measured before and after learning new skills, demonstrating that DSB before learning enhances cognitive performance compared to resting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Deep and Slow Breathing on Retention and Cognitive Function in the Elderly Population. Lee, SH., Park, DS., Song, CH.[2023]

Heart rate variability biofeedback (HRVB) training, particularly through resonance frequency (RF) breathing, significantly improves heart rate variability (HRV) and positive mood, as shown in a study with three groups of participants.

The RF breathing group exhibited a higher LF/HF HRV ratio and lower systolic blood pressure compared to the control group, indicating that RF breathing is an effective method for enhancing HRV and reducing stress responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Resonance Frequency Breathing on Measures of Heart Rate Variability, Blood Pressure, and Mood. Steffen, PR., Austin, T., DeBarros, A., et al.[2020]

A four-week training program of resonance breathing significantly improved heart rate variability (HRV) in young adults, indicating better health and stress adaptation, with specific improvements in HRV parameters like SDNN and pNN50.

Participants practicing resonance breathing also showed enhanced cognitive performance and reduced perceived stress levels, suggesting that this simple breathing technique can effectively alleviate anxiety and improve mental well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Resonance Breathing on Heart Rate Variability and Cognitive Functions in Young Adults: A Randomised Controlled Study. Chaitanya, S., Datta, A., Bhandari, B., et al.[2022]

In a study with 50 healthy participants, neurofeedback training (NFT) targeting the alpha rhythm significantly increased alpha amplitude and duration in the frontoparietal region, suggesting that alpha rhythm can be effectively trained.

Participants who underwent alpha NFT showed notable improvements in both working and episodic memory, particularly those with the greatest increases in alpha amplitude, indicating that this training may enhance cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback training of EEG alpha rhythm enhances episodic and working memory. Hsueh, JJ., Chen, TS., Chen, JJ., et al.[2023]

A study with 64 participants showed that 4 weeks of heart rate variability biofeedback (HRVB) training significantly increased heart rate variability (HRV) indices and decreased breathing rates compared to relaxation training.

The results indicated that at least 3 weeks of HRVB training is necessary to see improvements in HRV and breathing rates, highlighting the effectiveness of this intervention for enhancing autonomic nervous system function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four Sessions of Combining Wearable Devices and Heart Rate Variability (HRV) Biofeedback are Needed to Increase HRV Indices and Decrease Breathing Rates. Lin, IM., Chen, TC., Tsai, HY., et al.[2023]

Breathing at resonance frequency (RF) and RF + 1 breath per minute both significantly reduced muscle sympathetic nervous activity (MSNA) and improved cardiac baroreflex efficiency in ten healthy men, indicating beneficial effects on autonomic regulation.

While both breathing rates lowered systolic blood pressure, only RF showed a significant decrease, suggesting that breathing at RF may have a slightly greater impact on cardiovascular regulation compared to RF + 1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of resonance frequency breathing on cardiovascular regulation. Pagaduan, J., Wu, SS., Kameneva, T., et al.[2023]

In a study of 21 participants, the optimal breathing rate (resonance frequency, RF) for Heart Rate Variability Biofeedback (HRVB) was found to be unstable, changing in 66.7% of participants between test sessions, which suggests the need for individual assessment before each HRVB session.

Breathing at the individualized RF significantly increased heart rate variability (HRV) parameters (SDNN and RMSSD) compared to other breathing rates, indicating that personalized breathing techniques can maximize cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resonance frequency is not always stable over time and could be related to the inter-beat interval. Capdevila, L., Parrado, E., Ramos-Castro, J., et al.[2022]

Participants who underwent eight sessions of an adaptive neurofeedback protocol focused on modulating frontal-midline theta (FMθ) oscillations were able to significantly increase FMθ activity, indicating that neurofeedback can effectively enhance this brain activity associated with cognitive control.

The training led to improved cognitive performance, as evidenced by significantly faster reaction times on a working memory task, while no such improvements were observed in participants receiving sham neurofeedback, suggesting the efficacy of the FMθ-meditation neurofeedback protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-Loop Frontal Midlineθ Neurofeedback: A Novel Approach for Training Focused-Attention Meditation. Brandmeyer, T., Delorme, A.[2020]

In a study of 58 healthy older adults, cognitive training significantly improved performance on tasks, particularly in divided attention and speed-of-processing, with the most notable improvement seen in the Double Decision task.

The training led to strengthened connectivity in the frontoparietal control network, which was associated with better task performance, suggesting that this brain network plays a key role in the benefits of cognitive training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proximal improvement and higher-order resting state network change after multidomain cognitive training intervention in healthy older adults. Hardcastle, C., Hausman, HK., Kraft, JN., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Deep and Slow Breathing on Retention and Cognitive Function in the Elderly Population. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Resonance Frequency Breathing on Measures of Heart Rate Variability, Blood Pressure, and Mood. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of Resonance Breathing on Heart Rate Variability and Cognitive Functions in Young Adults: A Randomised Controlled Study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Neurofeedback training of EEG alpha rhythm enhances episodic and working memory. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Four Sessions of Combining Wearable Devices and Heart Rate Variability (HRV) Biofeedback are Needed to Increase HRV Indices and Decrease Breathing Rates. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Acute effects of resonance frequency breathing on cardiovascular regulation. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Resonance frequency is not always stable over time and could be related to the inter-beat interval. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Closed-Loop Frontal Midlineθ Neurofeedback: A Novel Approach for Training Focused-Attention Meditation. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Proximal improvement and higher-order resting state network change after multidomain cognitive training intervention in healthy older adults. [2023]