Effects of an 18-month meditation training on dynamic functional connectivity states in older adults: Secondary analyses from the Age-Well randomized controlled trial

Meditation training in older adults has been proposed as a non-pharmacological intervention to promote healthy aging and lower the risks of developing Alzheimer's disease (AD). Resting-state dynamic functional network connectivity (dFNC) highlighted two brain states, the "strongly connected" and "default mode network (DMN)-negatively connected" states, associated with protective factors for dementia including AD, and two states, the "weakly connected" and "salience-negatively connected" states, associated with risk factors for dementia. In this study, we aimed at assessing the impact of an 18-month meditation training on dFNC states in older adults. One hundred and thirty-five healthy older adults were randomized (1:1:1) to 18-month meditation training, 18-month non-native language training, or no intervention. dFNC of the DMN, salience, and executive control networks was assessed in 124 individuals using a sliding window framework, and states were obtained by k-means clustering. Linear mixed models evaluated the change in time spent in different connectivity "states" and the number of transitions between states for each group and between groups. Only participants in the meditation group transitioned significantly more between states (p = 0.008, d = 0.52), with a significant between-group difference with the non-native language training group (p = 0.001). Moreover, only the meditation group showed a change in time spent in specific states, spending less time in the "weakly connected" state (p = 0.009, d = -0.44) and more time in the "strongly connected" state (p = 0.03, d = 0.46), but there was no difference between groups. Brain states at rest were significantly impacted by an 18-month meditation intervention, with increased number of transitions between states, an increased time spent in the "strongly connected" state, and decreased time spent in the "weakly connected" state. While only the first change differed significantly between groups, these results suggest a beneficial effect of meditation through a reduction in dFNC metrics associated with AD risk factors and an increase in dFNC metrics associated with protective factors. However, the absence of a significant group-by-time interaction for time spent in states, the small effect sizes, and the fact that the sample size was not powered for this outcome limit the interpretation of the findings. Additionally, unmeasured factors such as genetic predisposition and lifestyle could have influenced the results. Future studies should identify the specific active mechanisms of meditation underlying these effects to optimize interventions. Trial Registration: The Age-Well randomized controlled trial (RCT) was approved by the local ethics committee (CPP Nord-Ouest III, Caen; trial registration number: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819; registration date: 2016-11-25).