Cognitive Aging
Conditions
Brief summary
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.
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.
Interventions
OTHERMeditation practice
18 months
OTHERLearning English as a foreign language
18 months
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Visit 1 inclusion - Visit 3 Month 18 | change in insula volume (T1-weighted MRI) |
| 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 | Visit 1 inclusion - Visit 3 Month 18 | change in anterior cingulate cortex volume (T1-weighted MRI) |
| 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 | Visit 1 inclusion - Visit 3 Month 18 | change in anterior cingulate cortex perfusion (early PET-Amyvid® scan) |
| 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 | Visit 1 inclusion - Visit 3 Month 18 | change in insula perfusion (early PET-Amyvid® scan) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Medical neuroimaging using MRI: brain perfusion in all brain voxels | up to 35 months post intervention | brain perfusion in all brain voxels |
| Medical neuroimaging using MRI: fractional anisotropy and mean diffusivity in all brain voxels | up to 35 months post intervention | fractional anisotropy and mean diffusivity in all brain voxels |
| Medical neuroimaging using MRI: number, size, type and location of white matter lesions | up to 35 months post intervention | number, size, type and location of white matter lesions |
| Medical neuroimaging using MRI: magnetic susceptibility index in all brain voxels | up to 35 months post intervention | magnetic susceptibility index in all brain voxels |
| Medical neuroimaging using MRI: brain functional connectivity measures in all brain voxels at rest in a non-meditative state | up to 35 months post intervention | brain functional connectivity measures in all brain voxels at rest in a non-meditative state |
| Beta-amyloid charge (of the radiopharmarceutical Amyvid®) measured in each voxel of the brain and gross mean in gray matter | up to 35 months post intervention | measured in each voxel of the brain and gross mean in gray matter |
| Glucose Cerebral Consumption at rest (relative to mean consumption measured in the cerebellum) | up to 35 months post intervention | Glucose Cerebral Consumption at rest (relative to mean consumption measured in the cerebellum) by TEP |
| Medical neuroimaging using fMRI: Brain activity specifically associated with emotional processes (comparing emotional to neutral items) during the Rest-SoVT task. | up to 35 months post intervention | Brain activity specifically associated with emotional processes (comparing emotional to neutral items) during the Rest-SoVT task. |
| Medical neuroimaging using fMRI: Brain activity specifically associated with attentional processes (altertness, inhibition, sustained attention) during the AX-CPT task. | up to 35 months post intervention | Brain activity specifically associated with attentional processes (altertness, inhibition, sustained attention) during the AX-CPT task. |
| Medical neuroimaging using PET-scan and Amyvid® radiotracer | up to 35 months post intervention | Brain amyloid load (of the PET-Amyvid® radiotracer) measured in global grey matter mask |
| Subjectives sleep measures with sleep quality index z-score mean of the scores at questionnaires | up to 35 months post intervention | Epworth scale, Leeds Sleep evaluation questionnaire, Pittsburg Sleep Quality Scale, St Mary's hospital questionnaire, Berlin Questionnaire, and Insomnia severity index. |
| Mean duration of sleep | up to 35 months post intervention | Data collected by actimetrics record |
| fragmentation indices during activity and resting states | up to 35 months post intervention | Data collected by actimetrics record |
| regularity of the rest-activity cycle | up to 35 months post intervention | Data collected by actimetrics record |
| Mean z-score of total sleep time | up to 35 months post intervention | Data collected during polysomnographic sleep record with Somno-Art device |
| Comparison between meditation intervention and language learning intervention on the global metacognitive composite score | up to 35 months post intervention | 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) |
| Mean z-score of sleep efficiency | up to 35 months post intervention | Data collected during polysomnographic sleep record with Somno-Art device |
| Biological blood tests | up to 35 months post intervention | tau, phosphotau, Ab 40, 42, APOE4, NFL, BDNF, GWAS, cytokines, CRP, cortisol, serotonine, SDHEA, SHBG, E2, testosterone, glycemie, insuline, BNP, tPA, PAI-1, peroxyredoxine |
| Telomerase properties by blood tests | visit 1 baseline -Visit 3 18 months | Telomerasic activity, telomerase length |
| lymphocytic immunophenotyping | visit 1 baseline -Visit 3 18 months | biological blood tests |
| Difference in partner perceptions of participant mindfulness measured by Five-Facet Mindfulness Questionnaire (FFMQ-15, range 15-75, higher scores indicate greater mindfulness) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant. |
| Difference in partner perceptions of participant compassion towards others measured by Compassionate Love Scale (Range 21-147, higher scores indicate greater compassion) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant |
| Difference in partner perceptions of participant depression measured by the Geriatric Depression Scale (range 0-15, higher scores indicate greater depressive symptoms) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant |
| Scores to evaluate the impact on volunteers' relatives | up to 35 months post intervention | 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 |
| 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) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant |
| Difference in partner perceptions of participant prosocialness measured by Prosocialness scale (range 16-80, higher scores indicate greater prosocialness) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant |
| 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) | up to 35 months post intervention | Partners are defined as spouse, sibling, child, neighbour or friend in close contact with the participant |
| 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) | up to 35 months post intervention | only for meditation experts |
| Safety and acceptance | up to 35 months post intervention | recording adverse events, measurement of anxiety, depression, satisfaction, and well-being using questionnaires |
| evaluation of the practice of the meditation practice and language learning at long-term (29 months post-intervention) | up to 35 months post intervention (because V4 = 29 months post intervention with a window of 6 months | questionnaire about the practice (meditation or foreign language) |
| Behavioral measures (questionnaires) to evaluate the psychological impact of the confinement | up to 35 months post intervention | composite score per function (anxiety, stress, auto-compassion...) |
| Mean z-score of sleep onset latency | up to 35 months post intervention | Data collected during polysomnographic sleep record with Somno-Art device |
| Composite score per cognitive area assessed by the neuropsychological tests and the questionnaires | up to 35 months post intervention | 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. |
| Medical neuroimaging using MRI: grey and white matter volume in all brain voxels | up to 35 months post intervention | grey and white matter volume in all brain voxels |
| Medical neuroimaging using MRI: hippocampal and hippocampal subfield volumes | up to 35 months post intervention | hippocampal and hippocampal subfield volumes |
Countries
France
Outcome results
None listed