Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). Objective: To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. Design, Setting, and Participants: This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Interventions: Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly. Main Outcomes and Measures: Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. Results: Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant. Conclusions and Relevance: In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02808676.

Effects of Brief Mindfulness Interventions on the Interference Induced by Experimental Heat Pain on Cognition in Healthy Individuals.

Background: Pain captures attention and interferes with competing tasks demanding cognitive effort. Brief mindfulness interventions involving both conceptual learning and meditation exercises have been shown to improve attention and reduce pain sensitivity, and could potentially reduce pain interference. This study assesses the effect of a 5-day mindfulness intervention (20 min/day) on the interference produced by thermal pain on working memory performance using a 2-back task. Methods: Healthy participants were randomized into three groups exposed to mindfulness meditation training (n = 15), an active educational control intervention comprising only conceptual information on mindfulness (n = 15), or no intervention (n = 15). The two active interventions were administered in a dual-blind fashion and outcomes were assessed by research personnel blind to this allocation. Evaluation sessions were conducted before and after the interventions to assess the effect of pain on 2-back performance (pain interference). Importantly, both pain stimuli and the 2-back task were calibrated individually and in each session before assessing pain interference, thereby controlling for possible changes in baseline pain sensitivity and cognitive performance. Secondary outcomes included heat pain sensitivity, cold pain tolerance, cognitive inhibition, cognitive flexibility, and divided attention. Results: Manipulation checks confirmed that heat pain interferes with the performance of the working-memory task. Compared to the no-intervention control group, pain interference was significantly reduced following the conceptual intervention but not the meditation intervention, although a corollary analysis suggests the effect might be due to regression toward the mean caused by baseline imbalance in pain interference. Secondary outcomes also suggested an increase in pain tolerance in the conceptual learning group only. Discussion: A short mindfulness meditation intervention was insufficient to reduce pain interference but conceptual learning about mindfulness produced some unexpected benefits. Although the generalization of experimental findings to clinical pain conditions may be premature, these results highlight the importance of distinguishing the contribution of mindfulness education and meditation training in future studies. Understanding the effects of mindfulness training on pain regulation and management must take into consideration the multiple factors underlying this complex intervention.

Effects of Dance/Movement Training vs. Aerobic Exercise Training on cognition, physical fitness and quality of life in older adults: A randomized controlled trial.

INTRODUCTION: It is generally accepted that physical activity promotes healthy aging. Recent studies suggest dance could also benefit cognition and physical health in seniors, but many styles and approaches of dance exist and rigorous designs for intervention studies are still scarce. The aim of this study was to compare the effects of Dance/Movement Training (DMT) to Aerobic Exercise Training (AET) on cognition, physical fitness and health-related quality of life in healthy inactive elderly. METHODS: A single-center, randomized, parallel assignment, open label trial was conducted with 62 older adults (mean age = 67.48 ±â€¯5.37 years) recruited from the community. Participants were randomly assigned to a 12-week (3x/week, 1hr/session) DMT program, AET program or control group. Cognitive functioning, physical fitness and health-related quality of life were assessed at baseline (T-0), and post-training (T-12 weeks). RESULTS: 41 participants completed the study. Executive and non-executive composite scores showed a significant increase post-training (F(1,37) = 4.35, p = .04; F(1,37) = 7.01, p = .01). Cardiovascular fitness improvements were specific to the AET group (F(2,38) = 16.40, p < .001) while mobility improvements were not group-dependent (10 m walk: F(1,38) = 11.67, p = .002; Timed up and go: F(1,38) = 22.07, p < .001). CONCLUSIONS: Results suggest that DMT may have a positive impact on cognition and physical functioning in older adults however further research is needed. This study could serve as a model for designing future RCTs with dance-related interventions. REGISTRATION: clinicaltrials. gov Identifier NCT02455258.

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment.

BACKGROUND: Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. METHODS: The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. DISCUSSION: The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. TRIAL REGISTRATION: Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .