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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Chételat, Lutz, Klimecki, Gonneaud, Poisnel, Collette, and Marchant have received research support from the European Union’s Horizon 2020 research and innovation programme under grant 667696. Drs Chételat, Lutz, Kuhn, Moulinet, and André have received support from their institution Institut National de la Santé et de la Recherche Médicale (Inserm). Dr Chételat has received research support from Fondation Alzheimer, Fondation Recherche Alzheimer, Région Normandie, Association France Alzheimer et maladies apparentées, and Fondation Vaincre Alzheimer and personal fees from Caen, Paris, Lyon and Nice Universities (salary for lectures), and Fondation Alzheimer (as member of the operational committee) outside the submitted work. Drs Chételat and Lutz have received research support from Fondation d’Entreprise MMA des Entrepreneurs du Futur and MMA (payments made to the institution). Dr Klimecki reported consulting companies and teaching meditation in addition to her scientific work. Dr Kuhn reported grants from French Ministry of Higher Education and Research (3 years of PhD, 2017-2020) during the conduct of the study and grants from Fondation Philippe Chatrier (2022 postdoctoral grant) outside the submitted work. Dr Touron reported grants from Ministry of Higher Education and Research (thesis grant, France) outside the submitted work. Dr André has received research support from Fonds Européen de Développement Régional (payment made to the institution). Dr Gonneaud reported grants from Fondation Alzheimer and Fondation de France, which covered her salary during the conduct of the study. Dr Vuilleumier reported grants from Swiss National Science Foundation and European Commission H2020 during the conduct of the study. Dr Poisnel reported grants and nonfinancial support from INSERM during the conduct of the study; grants from INSERM outside the submitted work; and has participated in the data safety monitoring board of the Age-Well trial and to the executive committee of Medit-Ageing. Dr Marchant received grants from Alzheimer’s Society and Medical Research Council (payment made to the institution) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Trial Profile

Of 137 randomized participants, 1 was excluded from all analyses due to major eligibility criteria not met (not included in the analyses), 1 died during follow-up, and 1 revealed not to have followed his allocated arm (randomized to no intervention but attended non-native language training); those 2 later participants were retained in the analyses and treated by the intention-to-treat principle, as specified in the statistical analysis plan. MRI indicates magnetic resonance imaging.

Figure 2.. Forest Plots for Anterior Cingulate Cortex (ACC) and Insula Volume and Perfusion

Results of the intention-to-treat analyses with missing = failure strategy are shown.

Figure 3.. Sensitivity Analyses for Anterior Cingulate Cortex (ACC) and Insula Volume and Perfusion

aNo missing outcome values for participants included in the comparison.