Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial

Abstract

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions.

Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults.

Design, setting, and participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020).

Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice.

Main outcomes and measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns.

Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention.

Conclusions and relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns.

Trial registration: ClinicalTrials.gov Identifier: NCT02665481.

Figure 1.. Participant Flow in a Study of the Effect of Mindfulness-Based Stress Reduction (MBSR) and Exercise on Cognitive Function

^aUnless individuals were screened, they were not fully assessed for eligibility; as such, the study team does not have the results (eg, why they were excluded or declined) for all of these individuals. ^bConditions that would suggest shortened lifespan or would prohibit safe participation in the interventions (eg, metastatic cancer, unstable cardiovascular disease) or would interfere with study assessments (eg, diabetes medication, systemic glucocorticoids, magnetic resonance imaging contraindications, severe hearing/visual impairment). ^cUnless they officially withdrew, participants who missed the 6-month assessment were not out of the study; they could rejoin for the 18-month assessment. ^dA higher number of participants (n = 36) in the health education intervention group were unable to complete the 18-month assessments due to the COVID-19 pandemic because of the randomization schedule (eg, these intervention groups were the last groups to be randomized in the trial). For example, 3 of the last 4 groups randomized in the trial were health education.

Figure 2.. Memory and Executive Function Composite Changes Over 18 Months

The composite scores were the standardized mean of several neuropsychological test scores for the domain of interest. A Z score was computed for each participant ([participant score − mean]/SD), using the mean and SD of that variable computed on all randomized participants at baseline. For example, the memory composite variable was created by the mean Z scores of all available memory variables. For composite interpretation purposes, if the intervention was effective in improving each individual measure that comprised the composite by 1 SD, the overall composite score would improve by 1 point (compared with the control). The ranges for memory and executive function are −3.3 to 3.7 and −5.0 to 3.0, respectively. See eTable 2 in Supplement 2 for numerical/model data of intervention effects. The boxplot inner horizontal lines represent the median values, the boxes represent the IQR (25% and 75%), the vertical whiskers extend to the upper and lower adjacent values (the furthest points within 1.5 IQRs of the 25th and 75th percentiles), and the dots indicate outlier values.

Figure 3.. Structural Brain Changes Over 18 Months

Shown are the mean of the right- and left-sided brain structures. The volumes of the brain regions in this article are somewhat dependent on the measurement technique; existing literature has found that both the volumes and their rate of change are consistent with studies in healthy aging. For example, Fraser et al found a rate of hippocampal atrophy of approximately 1% per year and Frangou et al reported a frontal cortical thickness change of 0.005 mm per year. These are within the range of changes reported in the current sample. The ranges for hippocampal volume, DLPFC surface area, and DLPFC cortical thickness are 2232 to 4926; 6642 to 16 992; and 2.0 to 3.7, respectively. See eTable 2 in Supplement 2 for numerical/model data of intervention effects. The boxplot inner horizontal lines represent the median values, the boxes represent the IQR (25% and 75%), the vertical whiskers extend to the upper and lower adjacent values (the furthest points within 1.5 IQRs of the 25th and 75th percentiles), and the dots indicate outlier values.