Cardiac-Control Affecting Learning Through Mindfulness (CALM)

Some types of meditation lead heart rate to become more steady as breathing quiets whereas others lead to large heart rate swings up and down (oscillations) as breathing becomes deeper and slower. The current study is designed to investigate how daily mindfulness practice with heart rate biofeedback during breathing in a pattern that either increases or decreases heart rate oscillation affect attention and memory and blood biomarkers associated with Alzheimer's disease.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Age-related Cognitive Decline
• Intervention / Treatment: Behavioral: Daily practice

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emotion & Cognition Lab Coordinator; Phone Number: 213-740-9543; Email: matherlab@usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089
      • Recruiting
      • University of Southern California
      • Contact: Emotion & Cognition Lab Coordinator; Phone Number: 213-740-9543; Email: matherlab@usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

• Fluent in English
• Black/African-American or White/European-American
• Aged between 50-70 years old
• Non-pregnant and non-menstruating (for at least the past year)
• Have normal or corrected-to-normal vision and hearing
• Have reliable access to wifi
• Have an email account that you check regularly
• Have a phone that receives text messages
• Agree to provide blood and urine samples at two campus visits
• Agree to devote up to 50 minutes daily to this study for 10 weeks as well as attend two campus visits

Exclusion criteria

• Have a disorder that would impede performing the breathing intervention (e.g., abnormal cardiac rhythm, arrhythmia, dyspnea)
• Have cognitive impairment
• Have regularly played Lumosity games in the past 6 months

• Have any conditions listed below that are not safe for MRI

  • *Metal in any parts of your body
  • Claustrophobia
  • Have worked as a machinist, metal worker, or in any profession or hobby grinding metal?
  • Have had an injury to the eye involving a metallic object (e.g., metallic slivers, shavings, or foreign body)
  • Cardiac pacemaker
  • Implanted cardiac defibrillator
  • Aneurysm clip or brain clip
  • Carotid artery vascular clamp
  • Neurostimulator
  • Insulin or infusion pump
  • Spinal fusion stimulator
  • Cochlear, otologic, ear tubes or ear implant
  • Prosthesis (eye/orbital, penile, etc.)
  • Implant held in place by a magnet
  • Heart valve prosthesis
  • Artificial limb or joint
  • Other implants in body or head
  • Electrodes (on body, head or brain)
  • Intravascular stents, filters
  • Shunt (spinal or intraventricular)
  • Vascular access port or catheters
  • IUD
  • Transdermal delivery system or other types of foil patches (e.g., Nitro, Nicotine, Birth control, etc.) that cannot be removed for MRI
  • Shrapnel, buckshot, or bullets
  • Tattooed eyeliner or eyebrows
  • Body piercing(s) that cannot be removed for MRI
  • Metal fragments (eye, head, ear, skin)
  • Internal pacing wires
  • Aortic clips
  • Metal or wire mesh implants
  • Wire sutures or surgical staples
  • Harrington rods (spine)
  • Bone/joint pin, screw, nail, wire, plate
  • Wig or toupee that cannot be removed for MRI
  • Hair implants that involve staples or metal
  • Hearing aid(s) that cannot be removed for MRI
  • Dentures or retainers that cannot be removed for MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Increase Oscillation; Participants will breath at a slow "resonance" frequency during a breath-focused mindfulness practice and receive biofeedback to increase heart rate oscillation.	Behavioral: Daily practice; Participants will be asked to undergo daily mindfulness practice while regulating (either increase or decrease) heart rate oscillation.
Experimental: Decrease Oscillation; Participants' breathing will not be fixed to particular frequency during a breath-focused mindfulness practice and they will receive biofeedback to decrease heart rate oscillation.	Behavioral: Daily practice; Participants will be asked to undergo daily mindfulness practice while regulating (either increase or decrease) heart rate oscillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma amyloid-beta 42 levels	Plasma Ab42 levels will be compared for Week 1 (pre-intervention) and Week 10 (post-intervention). Investigators will test for a time X condition interaction in plasma Ab 42 levels (to assess group differences in change).	Week 1 and Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma amyloid-beta 40 levels	Plasma Ab40 levels will be compared for Week 1 (pre-intervention) and Week 10 (post-intervention). Investigators will test for a time X condition interaction in plasma Ab 40 levels (to assess group differences in change).	Week 1 and Week 10
Plasma Ab42/40 ratio	Investigators will test for a time X condition interaction with plasma Ab42/40 ratio values as the dependent variable (to assess group differences in change).	Week 1 and Week 10
Change in brain perivascular space volume	Investigators will test for a time X condition interaction in perivascular space volume.	Week 1 and Week 10
Brain training performance on Lumosity games during the breathing intervention	Investigators will compute a general learning factor across performance on all games played daily during the intervention period (Weeks 2-10) and separately across performance on all games played daily before the intervention period (Week 1). Investigators will test for group differences in performance during the intervention, controlling for performance before the intervention.	During intervention (daily during Weeks 2-10) and before intervention (daily during Week 1)
Plasma pTau-181/tTau ratio	Investigators will test for a time X condition interaction with the ratio of pTau-181 and total tau values as the dependent variable (to assess group differences in change).	Week 1 and Week 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locus coeruleus (LC) responses to novel faces	Investigators will test for a time x condition interaction in phasic LC responses to novel faces during an fMRI face-name task.	Week 1 and Week 10

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Institute on Aging (NIA); University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: UP-21-00357-main; R01AG080652 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All individual scores associated with the primary and secondary outcomes will be shared.

Functional and structural brain images will be shared. Lumosity game play data will be shared.

• IPD Sharing Time Frame: IPD will be shared upon publication of results from those IPD with no end date.
• IPD Sharing Access Criteria: The investigators plan to use Openneuro.org, but if options change, the investigators may select another database. The plan is to have the data shared at a repository where those who are interested can access it. At Openneuro.org, all data are freely available to all users.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No