Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

Importance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. Objective: To investigate the effects of meditation training on brain integrity in older adults. Design, Setting, and Participants: Age-Well was a randomized, controlled superiority trial with blinded end point assessment. Community-dwelling cognitively unimpaired adults 65 years and older were enrolled between November 24, 2016, and March 5, 2018, in France. Participants were randomly assigned (1:1:1) to (1) an 18-month meditation-based training, (2) a structurally matched non-native language (English) training, or (3) no intervention arm. Analysis took place between December 2020 and October 2021. Interventions: Meditation and non-native language training included 2-hour weekly group sessions, practice of 20 minutes or longer daily at home, and 1-day intensive practices. Main Outcomes and Measures: Primary outcomes included volume and perfusion of anterior cingulate cortex (ACC) and insula. Main secondary outcomes included a global composite score capturing metacognitive, prosocial, and self-regulatory capacities and constituent subscores. Results: Among 137 participants (mean [SD] age, 69.4 [3.8] years; 83 [60.6%] female; 54 [39.4%] male) assigned to the meditation (n = 45), non-native language training (n = 46), or no intervention (n = 46) groups, all but 1 completed the trial. There were no differences in volume changes of ACC (0.01 [98.75% CI, -0.02 to 0.05]; P = .36) or insula (0.01 [98.75% CI, -0.02 to 0.03]; P = .58) between meditation and no intervention or non-native language training groups, respectively. Differences in perfusion changes did not reach statistical significance for meditation compared with no intervention in ACC (0.02 [98.75% CI, -0.01 to 0.05]; P = .06) or compared with non-native language training in insula (0.02 [98.75% CI, -0.01 to 0.05]; P = .09). Meditation was superior to non-native language training on 18-month changes in a global composite score capturing attention regulation, socioemotional, and self-knowledge capacities (Cohen d, 0.52 [95% CI, 0.19-0.85]; P = .002). Conclusions and Relevance: The study findings confirm the feasibility of meditation and non-native language training in elderly individuals, with high adherence and very low attrition. Findings also show positive behavioral effects of meditation that were not reflected on volume, and not significantly on perfusion, of target brain areas. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819.

Effects of a Mindfulness-Based Intervention versus Health Self-Management on Subclinical Anxiety in Older Adults with Subjective Cognitive Decline: The SCD-Well Randomized Superiority Trial.

INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a heightened risk of developing dementia and frequently experience subclinical anxiety, which is itself associated with dementia risk. OBJECTIVE: To understand whether subclinical anxiety symptoms in SCD can be reduced through behavioral interventions. METHODS: SCD-Well is a randomized controlled trial designed to determine whether an 8-week mindfulness-based intervention (caring mindfulness-based approach for seniors; CMBAS) is superior to a structurally matched health self-management program (HSMP) in reducing subclinical anxiety. Participants were recruited from memory clinics at 4 European sites. The primary outcome was change in anxiety symptoms (trait subscale of the State-Trait Anxiety Inventory; trait-STAI) from pre- to postintervention. Secondary outcomes included a change in state anxiety and depression symptoms postintervention and 6 months postrandomization (follow-up). RESULTS: One hundred forty-seven participants (mean [SD] age: 72.7 [6.9] years; 64.6% women; CMBAS, n = 73; HSMP, n = 74) were included in the intention-to-treat analysis. There was no difference in trait-STAI between groups postintervention (adjusted change difference: -1.25 points; 95% CI -4.76 to 2.25) or at follow-up (adjusted change difference: -0.43 points; 95% CI -2.92 to 2.07). Trait-STAI decreased postintervention in both groups (CMBAS: -3.43 points; 95% CI -5.27 to -1.59; HSMP: -2.29 points; 95% CI -4.14 to -0.44) and reductions were maintained at follow-up. No between-group differences were observed for change in state anxiety or depression symptoms. CONCLUSIONS: A time-limited mindfulness intervention is not superior to health self-management in reducing subclinical anxiety symptoms in SCD. The sustained reduction observed across both groups suggests that subclinical anxiety symptoms in SCD are modifiable. ClinicalTrials.gov identifier: NCT03005652.

The impact of meditation on healthy ageing - the current state of knowledge and a roadmap to future directions.

There is increasing evidence that meditation-based training promotes healthy ageing across many dimensions. This review summarizes the existing knowledge on the effects of meditation training on healthy ageing in the domains of emotions, cognition (with a special emphasis on attentional processes), and the preservation of related brain structures. Although evidence so far is promising, more rigorous randomized controlled studies with active control groups and long-term follow-up in older people are needed. We outline how these challenges can be addressed in future studies using the example of an ongoing project, Medit-Ageing (public name: Silver Santé Study), including two independent randomized controlled trials (RCT) as well as one cross-sectional study with meditation experts.

The Age-Well randomized controlled trial of the Medit-Ageing European project: Effect of meditation or foreign language training on brain and mental health in older adults.

INTRODUCTION: The Age-Well clinical trial is an ongoing monocentric, randomized, controlled trial aiming to assess an 18-month preventive meditation-based intervention directly targeting the attentional and emotional dimensions of aging to promote mental health and well-being in elderly people. METHODS: One hundred thirty-seven cognitively unimpaired older adults are randomized to either an 18-month meditation-based intervention, a structurally matched foreign language training, or a passive control arm. The impact of the intervention and underlying mechanisms are assessed with detailed cognitive, behavioral, biological, neuroimaging and sleep examinations. RESULTS: Recruitment began in late 2016 and ended in May 2018. The interventions are ongoing and will be completed by early 2020. DISCUSSION: This is the first trial addressing the emotional and cognitive dimension of aging with a long-term nonpharmacological approach and using comprehensive assessments to investigate the mechanisms. Results are expected to foster the development of preventive strategies reducing the negative impact of mental conditions and disorders.

The SCD-Well randomized controlled trial: Effects of a mindfulness-based intervention versus health education on mental health in patients with subjective cognitive decline (SCD).

INTRODUCTION: Subjectively experienced cognitive decline in older adults is an indicator of increased risk for dementia and is also associated with increased levels of anxiety symptoms. As anxiety is itself emerging as a risk factor for cognitive decline and dementia, the primary question of the present study is whether an 8-week mindfulness-based intervention can significantly reduce anxiety symptoms in patients with subjective cognitive decline (SCD). The secondary questions pertain to whether such changes extend to other domains of psychological, social, and biological functioning (including cognition, self-regulation, lifestyle, well-being and quality of life, sleep, and selected blood-based biomarkers) associated with mental health, older age, and risk for dementia. METHODS: SCD-Well is a multicenter, observer-blinded, randomized, controlled, superiority trial, which is part of the Horizon 2020 European Union-funded "Medit-Ageing" project. SCD-Well compares an 8-week mindfulness- and compassion-based intervention specifically adapted for older adults with SCD with a validated 8-week health education program. Participants were recruited from memory clinics in four European sites (Cologne, Germany; London, United Kingdom; Barcelona, Spain; and Lyon, France) and randomized with a 1:1 allocation, stratified by site. RESULTS: The primary outcome, change in anxiety symptoms, and secondary outcomes reflecting psychological, cognitive, social, and biological functioning are assessed at baseline, postintervention, and 4 months after the end of the intervention. DISCUSSION: The study will provide evidence on whether a mindfulness-based intervention can effect changes in anxiety and other risk factors for cognitive decline and dementia in older adults with SCD and will inform the establishment of intervention strategies targeted at improving mental health in older adults.

The Age-Well observational study on expert meditators in the Medit-Ageing European project.

INTRODUCTION: The Age-Well observational, cross-sectional study investigates the affective and cognitive mechanisms of meditation expertise with behavioral, neuroimaging, sleep, and biological measures sensitive to aging and Alzheimer's disease (AD). METHODS: Thirty cognitively unimpaired individuals aged 65 years or older with at least 10,000 hours of practice in mindfulness meditation (MM) and loving-kindness and compassion meditation (LKCM) are selected. The outcomes are the neuroimaging brain correlates of MM and LKCM and the assessments of long-term meditation practices on behavioral, neural, and biological measures as compared to nonmeditator older controls from the Age-Well randomized controlled trial. RESULTS: Recruitment and data collection began in late 2016 and will be completed by late 2019. DISCUSSION: Results are expected to foster the understanding of the effects of meditation expertise on aging and of the mechanisms of action underlying the meditation intervention in the Age-Well randomized controlled trial. These finding will contribute to the design of meditation-based prevention randomized controlled trials for the aged population and to the exploration of the possible long-time developmental trajectory of meditation training.

Reduced age-associated brain changes in expert meditators: a multimodal neuroimaging pilot study.

Aging is associated with progressive cerebral volume and glucose metabolism decreases. Conditions such as stress and sleep difficulties exacerbate these changes and are risk factors for Alzheimer's disease. Meditation practice, aiming towards stress reduction and emotion regulation, can downregulate these adverse factors. In this pilot study, we explored the possibility that lifelong meditation practice might reduce age-related brain changes by comparing structural MRI and FDG-PET data in 6 elderly expert meditators versus 67 elderly controls. We found increased gray matter volume and/or FDG metabolism in elderly expert meditators compared to controls in the bilateral ventromedial prefrontal and anterior cingulate cortex, insula, temporo-parietal junction, and posterior cingulate cortex /precuneus. Most of these regions were also those exhibiting the strongest effects of age when assessed in a cohort of 186 controls aged 20 to 87 years. Moreover, complementary analyses showed that these changes were still observed when adjusting for lifestyle factors or using a smaller group of controls matched for education. Pending replication in a larger cohort of elderly expert meditators and longitudinal studies, these findings suggest that meditation practice could reduce age-associated structural and functional brain changes.