• Eric J Lenze, Michelle Voegtle, J Philip Miller, Beau M Ances, David A Balota, Deanna Barch, Colin A Depp, Breno Satler Diniz, Lisa T Eyler, Erin R Foster, Torie R Gettinger, Denise Head, Tamara Hershey, Samuel Klein, Jeanne F Nichols, Ginger E Nicol, Tomoyuki Nishino, Bruce W Patterson, Thomas L Rodebaugh, Julie Schweiger, Joshua S Shimony, David R Sinacore, Abraham Z Snyder, Susan Tate, Elizabeth W Twamley, David Wing, Gregory F Wu, Lei Yang, Michael D Yingling, and Julie Loebach Wetherell.
• Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
• JAMA. 2022 Dec 13; 328 (22): 221822292218-2229.

ImportanceEpisodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions.ObjectiveTo determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults.Design, Setting, And ParticipantsThis 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).InterventionsParticipants 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 MeasuresThe 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.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT02665481.

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