Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well)

Interventional Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training and Foreign Language Learning on Behavioral, Biological and Neuroimaging Measures

As the number of older people in Europe grows, increasing healthy life years is a priority. As people live longer, ensuring good mental as well as physical health into later years is becoming ever more important. Cognitive decline, dementia (e.g. Alzheimer's Disease, AD), sleep disturbances and depression, all related to psychological distress and anxiety, are significant drivers of reduced quality of life in older adults. This project builds on evidence that meditation practice have the potential to downregulate these adverse factors and positively impact mental and neurological conditions including AD.

Study Overview

• Status: Completed
• Conditions: Cognitive Aging
• Intervention / Treatment: Other: Meditation practice; Other: Learning English as a foreign language

Detailed Description

Understanding of the neurocognitive mechanisms of meditation is still limited. Meditation can be conceptualized as "a set of complex emotional and attentional regulation strategies developed for a variety of purposes including the development of emotional well-being and balance". Affective (emotional) and cognitive (attentional) control are therefore the most likely mechanisms by which meditation could impact aging and AD. Specifically, meditation could enhance the controlling role of mid-brain structures and the executive network over structures involved in memory, emotions, and regulation of the immune system. This would lead to better emotional and cognitive control which in turn would be associated with improved mental and physical health.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Calvados
    • Caen, Calvados, France, 14000
      • GIP Cyceron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

1. Inclusion Criteria :

   For all participants

   • Age ≥ 65 years ;
   • To be autonomous
   • Live in their home;
   • Educational level ≥ 7 years (from the Preparatory Course (First grade) included);
   • To be registered to the social security system ;
   • To be motivated to effectively participate in the project and to sign the consent form in agreement with the local ethic committee ;
   • Neuropsychological performances within the normal range (according to age, sex, and educational level), as assessed by the diagnostic battery.

   For participants without previous meditation practice

   • French mother tongue;
   • Available for the trial duration (24 months);
   • Retired since 1 year or more;
   • No preference regarding the intervention group ;

   • Not having regularly or intensively practiced meditation or comparable practices (yoga, Qi Gong, Alexander technique) as follows :

     • more than one day per week for more than six months consecutively over the last 10 years,
     • intensively (internship or retreat > five consecutive days) over the past 10 years,
     • more than 25 days of retreats (cumulatively) prior to the last 10 years ;
   • Not speaking English fluently.

   For expert meditators :

   • Formal meditation practice > 10 000 hours in the whole life, including at least 6 cumulated months of retreat;
   • Daily meditation practice (at least 6 days/week, 45 minutes/day);
   • Mindfulness meditation practice (i.e. mindfulness, samatha/vipassana, zazen (zen), shikantaza (zen), focused attention, mahamudra/Dzogchen, and compassion/loving jindness (tonglen, metta/karuna, bodhichitta)

2. Exclusion criteria :

   • Contraindication to MRI or PET Amyvid® ;
   • For security reasons realted with the use of Amyvid®, a blood sampling allowing to measure hepatic and renal functions will be performed at the V1 visit before the PET-Amyvid® scan. In case anomalies are detected of grade 3 or higher severity, the PET-Amyvid® scan will not be performed.
   • Hypersensitivity to Amyvid®
   • History or presence of a major neurological or psychiatric disorder (including an addiction to alcohol or drugs);
   • History of cerebral disease (vascular, degenerative, physical malformation, tumor, or head trauma with loss of consciousness for more than an hour);
   • Presence of a chronic disease or acute unstable illness (respiratory, cardiovascular, digestive, renal, metabolic, hematologic, endocrine or infectious);
   • Current or recent medication that may interfere with cognitive action or radiological measures (psychotropic drugs, antihistamines, anti-Parkinsonian drugs, benzodiazepines, non-steroidal anti-inflammatory agents, antiepileptics, central analgesic and muscle relaxants);
   • Under legal guardianship or incapacitation;
   • Inclusion in another biomedical research protocol at baseline, if including use of a radiolabel for radiological measures;
   • Physical of behavioural inhabilities to perform the follow-up visits as planned in the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meditation program; Meditation courses and at-home practice	Other: Meditation practice; 18 months
Active Comparator: English learning courses; English learning courses and at-home practice	Other: Learning English as a foreign language; 18 months
No Intervention: No intervention; Follow-up without Meditation courses or English Learning courses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the effect of an 18-month meditation intervention in non-meditating senior participants on the volume of the anterior cingulate cortex compared to a passive control intervention	change in anterior cingulate cortex volume (T1-weighted MRI)	Visit 1 inclusion - Visit 3 Month 18
Estimate the effect of an 18-month meditation intervention in non-meditating senior participants on the perfusion of the anterior cingulate cortex compared to a passive control intervention	change in anterior cingulate cortex perfusion (early PET-Amyvid® scan)	Visit 1 inclusion - Visit 3 Month 18
Estimate the effect of an 18-month meditation intervention in non-meditating seniors on the volume of the insula compared to an 18 months intervention of learning a foreign language	change in insula volume (T1-weighted MRI)	Visit 1 inclusion - Visit 3 Month 18
Estimate the effect of an 18-month meditation intervention in non-meditating seniors on the perfusion of the insula compared to an 18 months intervention of learning a foreign language	change in insula perfusion (early PET-Amyvid® scan)	Visit 1 inclusion - Visit 3 Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison between meditation intervention and language learning intervention on the global metacognitive composite score	consisting in the mean of the attentional, constructive and deconstructive subscores (main behavioural outcome) Each composite score is computed by averaging its respective standardised scale scores (range (-3) - (4) , Higher score of the meditation composite score mean better outcome)	up to 35 months post intervention
Composite score per cognitive area assessed by the neuropsychological tests and the questionnaires	composite scores will be computed as z-scores calculated from all the cognitive scores obtained for the corresponding cognitive function that will have a normal distribution and will not have a floor or ceiling effect. Additional exploratory analyses will be conducted on all individual behavioural measures obtained.	up to 35 months post intervention
Medical neuroimaging using MRI: grey and white matter volume in all brain voxels	grey and white matter volume in all brain voxels	up to 35 months post intervention
Medical neuroimaging using MRI: hippocampal and hippocampal subfield volumes	hippocampal and hippocampal subfield volumes	up to 35 months post intervention
Medical neuroimaging using MRI: brain perfusion in all brain voxels	brain perfusion in all brain voxels	up to 35 months post intervention
Medical neuroimaging using MRI: fractional anisotropy and mean diffusivity in all brain voxels	fractional anisotropy and mean diffusivity in all brain voxels	up to 35 months post intervention
Medical neuroimaging using MRI: number, size, type and location of white matter lesions	number, size, type and location of white matter lesions	up to 35 months post intervention
Medical neuroimaging using MRI: magnetic susceptibility index in all brain voxels	magnetic susceptibility index in all brain voxels	up to 35 months post intervention
Medical neuroimaging using MRI: brain functional connectivity measures in all brain voxels at rest in a non-meditative state	brain functional connectivity measures in all brain voxels at rest in a non-meditative state	up to 35 months post intervention
Beta-amyloid charge (of the radiopharmarceutical Amyvid®) measured in each voxel of the brain and gross mean in gray matter	measured in each voxel of the brain and gross mean in gray matter	up to 35 months post intervention
Glucose Cerebral Consumption at rest (relative to mean consumption measured in the cerebellum)	Glucose Cerebral Consumption at rest (relative to mean consumption measured in the cerebellum) by TEP	up to 35 months post intervention
Medical neuroimaging using fMRI: Brain activity specifically associated with emotional processes (comparing emotional to neutral items) during the Rest-SoVT task.	Brain activity specifically associated with emotional processes (comparing emotional to neutral items) during the Rest-SoVT task.	up to 35 months post intervention
Medical neuroimaging using fMRI: Brain activity specifically associated with attentional processes (altertness, inhibition, sustained attention) during the AX-CPT task.	Brain activity specifically associated with attentional processes (altertness, inhibition, sustained attention) during the AX-CPT task.	up to 35 months post intervention
Medical neuroimaging using PET-scan and Amyvid® radiotracer	Brain amyloid load (of the PET-Amyvid® radiotracer) measured in global grey matter mask	up to 35 months post intervention
Subjectives sleep measures with sleep quality index z-score mean of the scores at questionnaires	Epworth scale, Leeds Sleep evaluation questionnaire, Pittsburg Sleep Quality Scale, St Mary's hospital questionnaire, Berlin Questionnaire, and Insomnia severity index.	up to 35 months post intervention
Mean duration of sleep	Data collected by actimetrics record	up to 35 months post intervention
fragmentation indices during activity and resting states	Data collected by actimetrics record	up to 35 months post intervention
regularity of the rest-activity cycle	Data collected by actimetrics record	up to 35 months post intervention
Mean z-score of total sleep time	Data collected during polysomnographic sleep record with Somno-Art device	up to 35 months post intervention
Mean z-score of sleep onset latency	Data collected during polysomnographic sleep record with Somno-Art device	up to 35 months post intervention
Mean z-score of sleep efficiency	Data collected during polysomnographic sleep record with Somno-Art device	up to 35 months post intervention
Biological blood tests	tau, phosphotau, Ab 40, 42, APOE4, NFL, BDNF, GWAS, cytokines, CRP, cortisol, serotonine, SDHEA, SHBG, E2, testosterone, glycemie, insuline, BNP, tPA, PAI-1, peroxyredoxine	up to 35 months post intervention
Telomerase properties by blood tests	Telomerasic activity, telomerase length	visit 1 baseline -Visit 3 18 months
lymphocytic immunophenotyping	biological blood tests	visit 1 baseline -Visit 3 18 months
Difference in partner perceptions of participant mindfulness measured by Five-Facet Mindfulness Questionnaire (FFMQ-15, range 15-75, higher scores indicate greater mindfulness)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant.	up to 35 months post intervention
Difference in partner perceptions of participant compassion towards others measured by Compassionate Love Scale (Range 21-147, higher scores indicate greater compassion)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant	up to 35 months post intervention
Difference in partner perceptions of participant depression measured by the Geriatric Depression Scale (range 0-15, higher scores indicate greater depressive symptoms)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant	up to 35 months post intervention
Scores to evaluate the impact on volunteers' relatives	scores to hetero questionnaires fulfilled by relatives and qualitative data from interviews with the participants on one hand and with the teachers on the other hand	up to 35 months post intervention
Difference in partner perceptions of participant anxiety measured by trait subscale of the state-trait anxiety inventory (trait-STAI, range 20-80, higher scores indicate greater anxiety symptoms)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant	up to 35 months post intervention
Difference in partner perceptions of participant prosocialness measured by Prosocialness scale (range 16-80, higher scores indicate greater prosocialness)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant	up to 35 months post intervention
Difference in partner perceptions of participant's cognitive difficulties in everyday life, measured by Mc Nair CDS (range 0-156, higher score indicates greater cognitive difficulties)	Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant	up to 35 months post intervention
Neural signature of meditative practices using brain medical imaging (neuronal activity in each cerebral voxel (fMRI) at rest and during the emotional task, in a mindfulness meditative state versus not; in compasional meditative state or not)	only for meditation experts	up to 35 months post intervention
Safety and acceptance	recording adverse events, measurement of anxiety, depression, satisfaction, and well-being using questionnaires	up to 35 months post intervention
evaluation of the practice of the meditation practice and language learning at long-term (29 months post-intervention)	questionnaire about the practice (meditation or foreign language)	up to 35 months post intervention (because V4 = 29 months post intervention with a window of 6 months
Behavioral measures (questionnaires) to evaluate the psychological impact of the confinement	composite score per function (anxiety, stress, auto-compassion...)	up to 35 months post intervention

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: De La Sayette Vincent, CHU Caen - France; Study Director: Chételat Gaël, GIP Cyceron Caen

Publications and helpful links

General Publications

• Demnitz-King H, Gonneaud J, Klimecki OM, Chocat A, Collette F, Dautricourt S, Jessen F, Krolak-Salmon P, Lutz A, Morse RM, Molinuevo JL, Poisnel G, Touron E, Wirth M, Walker Z, Chetelat G, Marchant NL; Medit-Ageing Research Group. Association of Self-reflection With Cognition and Brain Health in Cognitively Unimpaired Older Adults. Neurology. 2022 Sep 27;99(13):e1422-e1431. doi: 10.1212/WNL.0000000000200951. Epub 2022 Jul 19.
• Poisnel G, Arenaza-Urquijo E, Collette F, Klimecki OM, Marchant NL, Wirth M, de La Sayette V, Rauchs G, Salmon E, Vuilleumier P, Frison E, Maillard A, Vivien D, Lutz A, Chetelat G; Medit-Ageing Research Group. 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. Alzheimers Dement (N Y). 2018 Dec 14;4:714-723. doi: 10.1016/j.trci.2018.10.011. eCollection 2018.
• Felisatti F, Gonneaud J, Palix C, Garnier-Crussard A, Mezenge F, Landeau B, Chocat A, Quillard A, Ferrand-Devouge E, de La Sayette V, Vivien D, Chetelat G, Poisnel G; Medit-Ageing Research Group. Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults. Neurology. 2022 May 17;98(20):e2023-e2035. doi: 10.1212/WNL.0000000000200270. Epub 2022 Apr 13.
• Andre C, Rehel S, Kuhn E, Landeau B, Moulinet I, Touron E, Ourry V, Le Du G, Mezenge F, Tomadesso C, de Flores R, Bejanin A, Sherif S, Delcroix N, Manrique A, Abbas A, Marchant NL, Lutz A, Klimecki OM, Collette F, Arenaza-Urquijo EM, Poisnel G, Vivien D, Bertran F, de la Sayette V, Chetelat G, Rauchs G; Medit-Ageing Research Group. Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults: A Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol. 2020 Jun 1;77(6):716-724. doi: 10.1001/jamaneurol.2020.0311.
• Chetelat G, Lutz A, Klimecki O, Frison E, Asselineau J, Schlosser M, Arenaza-Urquijo EM, Mezenge F, Kuhn E, Moulinet I, Touron E, Dautricourt S, Andre C, Palix C, Ourry V, Felisatti F, Gonneaud J, Landeau B, Rauchs G, Chocat A, Quillard A, Devouge EF, Vuilleumier P, de La Sayette V, Vivien D, Collette F, Poisnel G, Marchant NL; Medit-Ageing Research Group. Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial. JAMA Neurol. 2022 Nov 1;79(11):1165-1174. doi: 10.1001/jamaneurol.2022.3185.
• Schlosser M, Klimecki OM, Collette F, Gonneaud J, Kliegel M, Marchant NL, Chetelat G, Lutz A; Medit-Ageing Research Group. An 18-month meditation training selectively improves psychological well-being in older adults: A secondary analysis of a randomised controlled trial. PLoS One. 2023 Dec 1;18(12):e0294753. doi: 10.1371/journal.pone.0294753. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2016
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 9, 2023

Study Registration Dates

• First Submitted: November 4, 2016
• First Submitted That Met QC Criteria: November 25, 2016
• First Posted (Estimated): November 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: C16-38; 2016-A01767-44 (Registry Identifier: ID RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data access of AGE-WELL and SCD-WELL studies of the MEDIT-AGEING project for which Institut national de la santé et de la recherche médicale (Inserm) is the sponsor. The Material can be mobilized, under the conditions and modalities defined in the Charter, by any research team belonging to an Academic signatory to the Consortium Agreement concluded for the needs of the Project or by any research team belonging to an Academic outside the Consortium Agreement, French or foreign, for carrying out SRP relating to the scientific theme of mental health and wellbeing in older people.

The Material may also be mobilized, by non-academic third parties for the realization of SRP relating to the scientific theme of mental health and wellbeing in older people, under conditions, in particular financial, which will be established by separate agreement between Inserm and by the said third party.

• IPD Sharing Time Frame: December 2020
• IPD Sharing Access Criteria: specific information (quantity of Data available on a given date, number of patients included in the Cohort meeting the specific selection criteria for SRP requests, etc.) necessary for the conception of the SRP request;; the price list for the mobilization of Data within the framework of the SRP.; the list of services likely to be performed by the signatories of the Consortium Agreement for the purposes of the SRP request, as well as the associated price list;; a quote for services not included in the price list.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL