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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
91
Participants will play a few brain training games using an online interface each day. These games train attention, memory and other cognitive functions.
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.
University of Southern California
Los Angeles, California, United States
Change in Plasma Amyloid Beta (Aβ) Levels
We computed an aggregate Z-score based on plasma Aβ40 and Aβ42 levels (pg/mL). A Z-score of 0 represents the sample mean. Higher values indicate a greater level of plasma Aβ, which in cognitively normal individuals has been found to be associated with a higher risk of converting to Alzheimer's disease (Song et al., 2011). This score was compared across three time points: Week 2 (pre-intervention), Week 7 (mid-intervention), and Week 12 (post-intervention). We conducted a time (Week 2, 7, 12) × condition ANOVA to test for a time × condition interaction in plasma Aβ levels, assessing group differences in change over time.
Time frame: Measured from blood draws at lab visits on Weeks 2, 7, and 12
Change in Plasma Ab42/40 Ratio
The plasma Aβ42/40 ratio was calculated by dividing the plasma Aβ42 concentration (pg/mL) by the plasma Aβ40 concentration (pg/mL) at each time point. We conducted a time (Week 2, 7, 12) × condition ANOVA to test for an interaction effect, using plasma Aβ42/40 ratio scores as the dependent variable to assess group differences over time. A higher Aβ42/40 ratio indicates a better outcome, reflecting greater brain clearance of Aβ.
Time frame: Measured from blood draws at lab visits on Weeks 2, 7, and 12
Change in Brain Perivascular Space Volume
We tested whether there were group differences in changes in perivascular space (PVS) volume. PVS volume was defined as the percentage of PVS volume relative to white matter volume in the centrum semiovale, our main region of interest.
Time frame: Measured from magnetic resonance imaging completed at lab visits on Weeks 2, 7, and 12
Change in Hippocampal Volume
We tested whether there were group differences in changes in hippocampal volume. We performed a two-way mixed ANCOVA on hippocampal volume, with condition as the between-subjects factor and time point (Week 2, 7, 12) as the within-subjects factor, controlling for intracranial volume as a covariate.
Time frame: Measured from magnetic resonance imaging completed at lab visits on Weeks 2, 7, and 12
Brain Training Performance on 12 Lumosity Games
Participants completed 12 brain-training games on the Lumosity platform (https://www.lumosity.com/) targeting six cognitive domains: Attention, Flexibility, Language, Math, Memory, and Reasoning. Performance scores were expressed in arbitrary units, with minimum scores generally in the hundreds. The exact lower limits vary across games, and the upper limits differ substantially between games. Across all games, higher scores indicate better cognitive performance. For analyses, standardized performance scores (z-scores) were derived from the raw Lumosity game scores. Scores were standardized within each game across all participants; therefore, some values may appear negative, reflecting scores below the sample mean. A z-score of 0 represents the sample mean, with higher z-scores indicating better cognitive function. Standardized scores across games were combined using Partial Least Squares Correlation (PLSC) analyses.
Time frame: Measured at pre-intervention during week 2 and at the end of the intervention during week 12
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