Heartrate and Breathing Effects on Attention and Memory

Study Overview
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Brief Summary
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In the current study, we will examine how daily paced breathing affects plasma amyloid beta levels and the rate of learning in older adults. Healthy adults aged 50-70 who meet all eligibility criteria will be invited to this study. Participants will be randomly assigned to one of the two conditions: 1) Daily memory and attention training followed by a paced breathing protocol designed to increase relaxation or 2) Daily memory and attention training followed by a paced breathing protocol to increase alertness. Participants will be asked to complete pre and post intervention cognitive testing online, engage in 10 weeks of daily brain training (starting Week 2) and 9 weeks of paced breathing (starting Week 3) at home. They will also be asked to come in for lab visits on Weeks 2, 7 and 12 to provide blood and urine samples to assess amyloid beta levels and to complete magnetic resonance imaging scans to assess perivascular space volume.

Official Title
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Heartrate and Breathing Effects on Attention and Memory

Conditions
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Aging, Alzheimer Disease, Age-related Cognitive Decline

Intervention / Treatment
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* Behavioral: Brain training
* Behavioral: Paced breathing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: speak English fluently between the age of 50-70 healthy adult who weighs at least 110 pounds non-pregnant and non-menstruating (for at least the past year) normal or corrected-to-normal vision and hearing have a home computer with a physical keyboard and have access to reliable internet have an email account that you check regularly have a phone that receives text messages willing to provide a blood sample and a urine sample at three lab visits willing to devote up to 60 minutes daily to the study for 12 weeks (in addition to lab visits) Exclusion Criteria: have a disorder that would impede performing the breathing intervention (e.g., abnormal cardiac rhythm, heart disease including coronary artery disease, angina, and arrhythmia, cognitive impairment, dyspnea) regularly practicing any relaxation, biofeedback, or breathing technique (e.g., meditation) for more than an hour a week regularly played Lumosity games in the past 6 months participated in heart rate biofeedback studies in the USC Emotion & Cognition Lab have any conditions listed below that are not safe for MRI 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brain training and paced breathing to stimulate alertness<br> | Behavioral: Brain training<br>* Participants will play a few brain training games using an online interface each day. These games train attention, memory and other cognitive functions.<br>Behavioral: Paced breathing<br>* After completing brain training, they will then immediately do one 15-minute session of paced breathing, followed by a second 15-min session of paced breathing later in the day. During the paced breathing sessions, participants will clip a pulse monitor to their ear lobe and try to inhale and exhale in synchrony with a ball that moves up and down on the screen. They will receive heart rate biofeedback regarding whether they are achieving their relaxation/alertness goal.<br>|
| Experimental: Brain training and paced breathing to relax<br> | Behavioral: Brain training<br>* Participants will play a few brain training games using an online interface each day. These games train attention, memory and other cognitive functions.<br>Behavioral: Paced breathing<br>* After completing brain training, they will then immediately do one 15-minute session of paced breathing, followed by a second 15-min session of paced breathing later in the day. During the paced breathing sessions, participants will clip a pulse monitor to their ear lobe and try to inhale and exhale in synchrony with a ball that moves up and down on the screen. They will receive heart rate biofeedback regarding whether they are achieving their relaxation/alertness goal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma amyloid beta levels | We will compute an aggregate score based on both plasma Ab40 and Ab42 levels. This score will be compared for Week 2 (pre-intervention), Week 7 (during intervention) and Week 12 (post intervention). We will conduct a time (Week 2, 7, 12) X condition ANOVA to test for a time X condition interaction in plasma Ab levels (to assess group differences in change). | Measured from blood draws at lab visits on Weeks 2, 7, and 12 | 
| Change in plasma Ab42/40 ratio [ Time Frame: Measured from blood draws at lab visits on Weeks 2, 7, and 12 ] | We will conduct a time (Week 2, 7, 12) X condition ANOVA to test for a time X condition interaction with plasma Ab42/40 ratio scores as the dependent variable (to assess group differences in change). | Measured from blood draws at lab visits on Weeks 2, 7, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain perivascular space volume | We will test whether there are group differences in change in perivascular space volume | Measured from magnetic resonance imaging completed at lab visits on Weeks 2, 7, and 12 | 
| Change in hippocampal volume | We will test whether there are group differences in change in hippocampal volume | Measured from magnetic resonance imaging completed at lab visits on Weeks 2, 7, and 12 | 
| Brain training performance on 12 Lumosity games during the breathing intervention (controlling for brain training performance pre intervention) | We will compute a general learning factor across performance on all 12 games played daily during the intervention period (Weeks 3-11). We will also assess game performance in the pre-intervention Week 2 to provide a baseline performance measure for each participant and statistically account for it. | Pre intervention (daily during Week 2) and during intervention (daily during Weeks 3-11) |