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

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.

Mindfulness Training for Depressed Older Adults Using Smartphone Technology: Protocol for a Fully Remote Precision Clinical Trial.

BACKGROUND: Precision medicine, optimized interventions, and access to care are catchphrases for the future of behavioral treatments. Progress has been slow due to the dearth of clinical trials that optimize interventions' benefits, individually tailor interventions to meet individual needs and preferences, and lead to rapid implementation after effectiveness is demonstrated. Two innovations have emerged to meet these challenges: fully remote trials and precision clinical trials. OBJECTIVE: This paper provides a detailed description of Mindful MyWay, a study designed to test online mindfulness training in older adults with depression. Consistent with the concept of fully remote trials using a smartphone app, the study requires no in-person contact and can be conducted with participants anywhere in the United States. Based upon the precision medicine framework, the study assesses participants using high-frequency assessments of symptoms, cognitive performance, and patient preferences to both understand the individualized nature of treatment response and help individually tailor the intervention. METHODS: Mindful MyWay is an open-label early-phase clinical trial for individuals 65 years and older with current depression. A smartphone app was developed to help coordinate the study, deliver the intervention, and evaluate the acceptability of the intervention, as well as predictors and outcomes of it. The curriculum for the fully remote intervention parallels the mindfulness-based stress reduction curriculum, a protocolized group-based mindfulness training that is typically provided in person. After consent and screening, participants download The Healthy Mind Lab mobile health smartphone app from the Apple App Store, allowing them to complete brief smartphone-based assessments of depressive symptoms and cognitive performance 4 times each day for 4 weeks prior to and after completing the intervention. The intervention consists of an introduction video and 10 weekly mindfulness training sessions, with the expectation to practice mindfulness at home daily. The app collects participant preference data throughout the 10-week intervention period; these high-frequency assessments identify participants' individually dynamic preferences toward the goal of optimizing the intervention in future iterations. RESULTS: Participant recruitment and data collection began in March 2019. Final end point assessments will be collected in May 2022. The paper describes lessons learned regarding the critical role of early-phase testing prior to moving to a randomized trial. CONCLUSIONS: The Mindful MyWay study is an exemplar of innovative clinical trial designs that use smartphone technology in behavioral and neuropsychiatric conditions. These include fully remote studies that can recruit throughout the United States, including hard-to-access areas, and collect high-frequency data, which is ideal for idiographic assessment and individualized intervention optimization. Our findings will be used to modify our methods and inform future randomized controlled trials within a precision medicine framework. TRIAL REGISTRATION: ClinicalTrials.gov NCT03922217; https://clinicaltrials.gov/ct2/show/NCT03922217. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39233.

Mindfulness-Based Stress Reduction in Older Individuals: Who Benefits the Most?

Background: Preexisting patient characteristics may influence the outcome of mindfulness training, and a composite predictive index may be most informative in predicting outcome. Primary Study Objective: To develop a predictive index from baseline patient characteristics to determine which characteristics are associated with improvement following mindfulness-based stress reduction (MBSR) vs health education and to examine whether intreatment variables-reflecting adherence to the mindfulness intervention-predicted clinical outcome. Methods: In a secondary data analysis, a composite moderator statistical approach created a predictive index from baseline participant characteristics that were associated with clinical global impressions improvement following intervention. Setting: Data come from a 2-site, randomized controlled trial which took place in medical centers in St Louis, Missouri, and San Diego, California. Participants: Included 103 older adults with anxiety and/or depressive disorders randomized to either 8 sessions of MBSR or health education classes. Intervention: MBSR was delivered in 8 sessions of 2 hours each by credentialed health care providers. The control condition consisted of health education classes designed to match the length and timing of the MBSR sessions. Primary Outcome Measures: The Clinical Global Impressions-Improvement scale was used to measure symptom improvement and was assigned by a blind rater. Results: The combined moderator approach generated a predictive index with a moderate effect size (0.46; 95% CI: 0.35, 0.57). Individuals who demonstrated improvement on the scale following MBSR were more likely to be younger, female, with lower psychological symptom severity, and less likely to have a diagnosis of depression or to be taking selective serotonin reuptake inhibitors. Discussion: Baseline characteristics predicted clinical response with MBSR in older adults. These predictive factors, if replicated and validated, could determine which patients are most likely to benefit from mindfulness training and lead to personalized strategies to maximize outcomes. The study was registered on ClinicalTrials.gov (identifier: NCT01693874).

Covariance and Correlation Analysis of Resting State Functional Magnetic Resonance Imaging Data Acquired in a Clinical Trial of Mindfulness-Based Stress Reduction and Exercise in Older Individuals.

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar factor. We apply this methodology to the analysis of a large, resting state fMRI data set acquired in a prospective, controlled study of mindfulness training and exercise in older, sedentary participants at risk for developing cognitive decline. Results show marginally significant effects of both mindfulness training and exercise in both covariance and correlation measures of functional connectivity.

Enhancing Cognition in Older Persons with Depression or Anxiety with a Combination of Mindfulness-Based Stress Reduction (MBSR) and Transcranial Direct Current Stimulation (tDCS): Results of a Pilot Randomized Clinical Trial.

Objectives: Individuals with subjective memory complaints and symptoms of depression and/or anxiety are at high risk for further cognitive decline, and possible progression to dementia. Low-burden interventions to help slow or prevent cognitive decline in this high-risk group are needed. The objective of this study is to assess the feasibility of combining Mindfulness-Based Stress Reduction (MBSR) with transcranial direct current stimulation (tDCS) to increase putative benefits of MBSR for cognitive function and everyday mindfulness in depressed or anxious older adults with subjective cognitive decline. Methods: We conducted a two-site pilot double-blind randomized sham-controlled trial, combining active MBSR with either active or sham tDCS. The intervention included weekly in-class group sessions at the local university hospital and daily at-home practice. Anodal tDCS was applied for 30 min during MBSR meditative practice, both in-class and at-home. Results: Twenty-six individuals with subjective cognitive complaints and symptoms of depression and/or anxiety were randomized to active (n = 12) or sham tDCS (n = 14). The combination of MBSR and tDCS was safe and well tolerated, though at-home adherence and in-class attendance were variable. While they were not statistically significant, the largest effect sizes for active vs. sham tDCS were for everyday mindfulness (d = 0.6) and social functioning (d = 0.9) (F (1,21) = 3.68, p = 0.07 and F (1,21) = 3.9, p = 0.06, respectively). Conclusions: Our findings suggest that it is feasible and safe to combine tDCS with MBSR in older depressed and anxious adults, including during remote, at-home use. Furthermore, tDCS may enhance MBSR via transferring its meditative learning and practice into increases in everyday mindfulness. Future studies need to improve adherence to MBSR with tDCS. Trial Registration: ClinicalTrials.gov (NCT03653351 and NCT03680664). Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-021-01764-9.

Effectiveness of non-pharmacological interventions for treating post-stroke depressive symptoms: Systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the effectiveness of non-pharmacological interventions on depressive symptoms in people after stroke. DATA SOURCES: A literature search was performed through databases from January 2000 to August 2018: MEDLINE; CINAHL Plus; Scopus; Academic Search Complete; Cochrane Central Register of Controlled Trials; Scopus; and Library, Information Science and Technology Abstracts. Search terms included depression, stroke, non-pharmacologic, and intervention. STUDY SELECTION: We included randomized controlled trials comparing non-pharmacological interventions to controls for depressive symptoms in people after stroke. Of 1703 identified articles, 22 trials were included in narrative synthesis, of which 13 were eligible for meta-analysis. DATA EXTRACTION: Two reviewers extracted characteristics of participants, interventions, and results from all included trials. DATA SYNTHESIS: Thirteen interventions were categorized into four types: complementary and alternative therapy (five trials, n=228), exercise (four trials, n=263), psychosocial therapy (two trials, n=216), and multifactorial therapy (two trials, n=358). Overall beneficial effects of non-pharmacological interventions on depressive symptoms were found both post-intervention (effect size [ES] = -0.24, 95% confidence Interval [CI]: -0.37 to -0.11, p < 0.05) and at follow-up (ES = -0.22, CI: -0.36 to -0.07, p< 0.05). We found individual beneficial effects for complementary and alternative therapy (ES = -0.29, CI: -0.55 to -0.02, p < 0.05) and psychosocial therapy (ES = - 0.33, CI: -0.60 to -0.06, p < 0.05) post-intervention. CONCLUSIONS: Complementary and alternative therapy and psychosocial therapy appear to be promising strategies for improving post-stroke depression. Future studies target  a personalized approach for people with specific conditions such as cognitive impairment.

Mindfulness, Education, and Exercise for age-related cognitive decline: Study protocol, pilot study results, and description of the baseline sample.

BACKGROUND/AIMS: Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions. METHODS: Here, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions-mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone-compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments. RESULTS: We provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585). CONCLUSION: When complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.

Does patient expectancy account for the cognitive and clinical benefits of mindfulness training in older adults?

OBJECTIVES: Patient expectations of treatment effects could influence neuropsychological and clinical outcomes in clinical trials of behavioral and lifestyle interventions, which could potentially confound the interpretation of findings. Our aim was to examine whether patient expectancy mediated effectiveness of Mindfulness-Based Stress Reduction (MBSR) for improving cognitive function and clinical outcome. METHODS: The present study uses data from a single-blind, multi-site, randomized controlled trial comparing MBSR to a health education attention control in older adults with anxiety and/or depressive disorders and subjective cognitive concerns. Using the Credibility and Expectations Questionnaire, we measured expectancy and perceived credibility of the interventions assigned to patients. Using mediational analysis, we examined the influence of expectancy and credibility on two key outcomes: memory performance and clinical global improvement. RESULTS: Neither expectancy nor perceived credibility of intervention accounted significantly for MBSR's effectiveness for memory test performance or clinical global improvement. CONCLUSION: In this clinical trial, expectancy for improvement did not account for the effectiveness of MBSR on memory performance or clinical outcomes in depressed and anxious older adults. We advise that clinical trials of behavioral and lifestyle interventions for brain health in older adults should measure and test the role of expectancy.

A qualitative study of older adults' perspectives on initiating exercise and mindfulness practice.

BACKGROUND: Mindfulness practice and exercise are ways by which older adults can improve and maintain their physical, emotional and cognitive health. METHODS: This single-site qualitative study gathered insights of older adults' perceptions about initiating and maintaining mindfulness and exercise practices. We carried out focus groups with 41 adults aged 65-85 who had recently initiated Mindfulness Based Stress Reduction (MBSR), structured exercise, or their combination as part of participation in a clinical trial. We used a semi-structured interview to ask them open-ended questions regarding the benefits, barriers and facilitators of participating in mindfulness and/or exercise interventions. The interview also included questions regarding translation of these practices into community settings as well as the long-term maintenance potential of these practices. RESULTS: Older adults indicated that the mindfulness training increased their awareness and self-reflection and fostered a more self-accepting attitude. Furthermore, they improved their self-care habits and reported having better familial and social relationships. The main barrier for both the exercise and Mindfulness group was time management. The social benefits and sense of community were some of the primary motivators for older adults in the exercise and/or MBSR interventions. However, the research on how to motivate older adults to initiate healthy behavioral changes also needs to be answered. The benefits of exercise and MBSR are a motivation in and of themselves, as indicated by some of the participants. CONCLUSIONS: This study indicates that mindfulness training and exercise can serve as tools to cultivate important health lifestyle qualities among older adults, who are in the midst of mental, social, emotional and physical change. If it were not for the purpose of the research or the incentives provided by the research team, these older adults may have never started the healthy behavioral changes. From the responses, this may indicate that older adults may need more incentives to begin and maintain behavioral changes other than for their own health benefit.

Mindfulness-Based Stress Reduction for Older Adults With Stress Disorders and Neurocognitive Difficulties: A Randomized Controlled Trial.

OBJECTIVE: To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. METHODS: 103 adults aged 65 years or older with an anxiety or depressive disorder (diagnosed according to DSM-IV criteria) and subjective neurocognitive difficulties were recruited in St. Louis, Missouri, or San Diego, California, from September 2012 through August 2013 and randomly assigned in groups of 5-8 to mindfulness-based stress reduction (MBSR) or a health education control condition matched for time, attention, and credibility. The primary outcomes were memory (assessed by immediate and delayed paragraph and list recall) and cognitive control (Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test). Other outcomes included clinical symptoms (worry, depression, anxiety, and global improvement). HPA axis activity was assessed using peak salivary cortisol. Outcomes were measured immediately post-intervention and (for clinical outcomes only) at 3- and 6-month follow up. RESULTS: On the basis of intent-to-treat principles using data from all 103 participants, the mindfulness group experienced greater improvement on a memory composite score (P = .046). Groups did not differ on change in cognitive control. Participants receiving MBSR also improved more on measures of worry (P = .042) and depression (P = .049) at posttreatment and on worry (P = .02), depression (P = .002), and anxiety (P = .002) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale (47% vs 27%, χ² = 4.5, P = .03). Cortisol level decreased to a greater extent in the mindfulness group, but only among those participants with high baseline cortisol. CONCLUSIONS: In this population of older adults with stress disorders and neurocognitive difficulties, a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01693874.

Ecological momentary assessment versus standard assessment instruments for measuring mindfulness, depressed mood, and anxiety among older adults.

As mobile data capture tools for patient-reported outcomes proliferate in clinical research, a key dimension of measure performance is sensitivity to change. This study compared performance of patient-reported measures of mindfulness, depression, and anxiety symptoms using traditional paper-and-pencil forms versus real-time, ambulatory measurement of symptoms via ecological momentary assessment (EMA). Sixty-seven emotionally distressed older adults completed paper-and-pencil measures of mindfulness, depression, and anxiety along with two weeks of identical items reported during ambulatory monitoring via EMA before and after participation in a randomized trial of Mindfulness-Based Stress Reduction (MBSR) or a health education intervention. We calculated effect sizes for these measures across both measurement approaches and estimated the Number-Needed-to-Treat (NNT) in both measurement conditions. Study outcomes greatly differed depending on which measurement method was used. When EMA was used to measure clinical symptoms, older adults who participated in the MBSR intervention had significantly higher mindfulness and significantly lower depression and anxiety than participants in the health education intervention at post-treatment. However, these significant changes in symptoms were not found when outcomes were measured with paper-and-pencil measures. The NNT for mindfulness and depression measures administered through EMA were approximately 25-50% lower than NNTs derived from paper-and-pencil administration. Sensitivity to change in anxiety was similar across administration modes. In conclusion, EMA measures of depression and mindfulness substantially outperformed paper-and-pencil measures with the same items. The additional resources associated with EMA in clinical trials would seem to be offset by its greater sensitivity to detect change in key outcome variables.

Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus.

OBJECTIVE: To evaluate the impact of a Mindfulness Based Stress Reduction (MBSR) program in patients with chronic bothersome tinnitus on the (1) severity of symptoms of tinnitus and (2) functional connectivity in neural attention networks. STUDY DESIGN: Open-label interventional pilot study. SETTING: Outpatient academic medical center. SUBJECTS: A total of 13 adult participants with a median age of 55 years, suffering from bothersome tinnitus. METHODS: An 8-week MBSR program was conducted by a trained MBSR instructor. The primary outcome measure was the difference in patient-reported tinnitus symptoms using the Tinnitus Handicap Index (THI) and Tinnitus Functional Index (TFI) between pre-intervention, post-MBSR, and 4-week post-MBSR assessments. Secondary outcomes included change in measurements of depression, anxiety, mindfulness, and cognitive abilities. Functional connectivity magnetic resonance imaging (MRI) was performed at pre- and post-MBSR intervention time points to serve as a neuroimaging biomarker of critical cortical networks. RESULTS: Scores on the THI and TFI showed statistically significant and clinically meaningful improvement over the course of the study with a median ΔTHI of -16 and median ΔTFI of -14.8 between baseline and 4-week follow-up scores. Except for depression, there was no significant change in any of the secondary outcome measures. Analysis of the resting state functional connectivity MRI (rs-fcMRI) data showed increased connectivity in the post-MBSR group in attention networks but not the default network. CONCLUSION: Participation in an MBSR program is associated with decreased severity in tinnitus symptoms and depression and connectivity changes in neural attention networks. MBSR is a promising treatment option for chronic bothersome tinnitus that is both noninvasive and inexpensive.

Mindfulness-based stress reduction for older adults with worry symptoms and co-occurring cognitive dysfunction.

BACKGROUND: Mindfulness-based stress reduction (MBSR) has the potential to reduce worry and improve cognitive functioning. OBJECTIVES: In this treatment development project, we examined MBSR in older adults with worry symptoms and co-occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii) whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's benefits for worry reduction and cognitive improvements, and (iv) continued use of MBSR techniques during follow-up. METHODS: Two sites (St. Louis and San Diego) enrolled individuals aged 65 years or older with significant anxiety-related distress plus subjective cognitive dysfunction, into traditional 8-session MBSR groups and 12-session groups that had the same content but more repetition of topics and techniques. We examined measures of mindfulness, worry, and a neuropsychological battery focused on memory and executive function before and after the MBSR program, and we followed up participants for 6 months after the completion of MBSR regarding their continued use of its techniques. RESULTS: Participants (N = 34) showed improvements in worry severity, increases in mindfulness, and improvements in memory as measured by paragraph learning and recall after a delay, all with a large effect size. Most participants continued to use MBSR techniques for 6 months post-instruction and found them helpful in stressful situations. There was no evidence that the extended 12-week MBSR produced superior cognitive or clinical outcomes, greater satisfaction, or greater continuation of MBSR techniques than 8-week MBSR. CONCLUSIONS: These preliminary findings are promising for the further testing and use of MBSR in older adults suffering from clinical worry symptoms and co-occurring cognitive dysfunction. These are common problems in a broad range of older adults, many of whom have anxiety and mood disorders; therefore, stress reduction intervention for them may have great public health value.

More than just a pill. How to include psychosocial approaches sin the treatment of anxiety & depressive disorders.

Anxiety and depressive disorders are the most common psychiatric disorders, causing high personal and economic burden. Psychosocial approaches, such as psychotherapy or mind-body instruction, along with self-help approaches, exercise, and proper sleep hygiene are effective solo or additive (to pharmacotherapy) strategies. Many physicians are less familiar with these methods for treating anxiety/depressive disorders. This article seeks to illuminate psychosocial approaches for depression and anxiety that act additively or independently of pharmacotherapy and explain how physicians can utilize them.