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Meditation as a tool to prevent dementia and improve the mental health and well-being of elderly people is one of the avenues explored by the European Medit-Ageing research program, coordinated by Inserm. As part of this program, researchers from Inserm and Université de Caen Normandie, in collaboration with French and European teams, observed the impact of 18 months of meditation training on certain brain structures involved in regulating attention and emotions in healthy people over 65. While their findings, to be published in JAMA Neurology, show a positive impact on attentional and socio-emotional regulation capacities, they do not show any significant benefits of meditation on the volume and functioning of the brain structures studied, in comparison to control groups. However, they do call for further research to study the brain as a whole, over longer time periods, and with more participants.

In order to prevent the onset of dementia in elderly people, recent intervention strategies have been multidisciplinary and focused on lifestyle improvements. These include cognitive stimulation, physical activity, a healthy diet, and cardiovascular recommendations. However, there are no dedicated preventive interventions for psycho-affective factors such as depression, stress, and anxiety.

Mental training aimed at regulating stress and attention, such as mindful meditation, has proven to be beneficial in managing the cognitive and emotional aspects of aging, particularly to reduce stress, anxiety, and depression.

Recent research has reported that the insula and anterior cingulate cortex are brain regions particularly sensitive to meditation training. These interconnected regions are involved in self-awareness and in the processing and regulation of attention, emotions, and empathy. In young adults, meditation has already shown its capacity to structurally (e.g. in terms of volume) and functionally modify these structures, particularly in the brain of meditation experts with several thousand hours of practice under their belts.

The insula and anterior cingulate cortex are particularly sensitive to aging. It has been shown that in elderly people who are experts in meditation, gray matter volume and glucose metabolism (a physiological process essential for good brain function) were higher than in people who do not meditate.

Meditation could therefore be an interesting approach to preserve brain structures, functions, and cognitive capacities, and by extension, prevent dementia.

A team of researchers from the European Medit-Ageing research group, led by Inserm Research Director Gaël Chételat from the Physiopathology and Imaging of Neurological Disorders laboratory (Inserm/Université de Caen Normandy), in collaboration with teams from Lyon Neuroscience Research Center (Inserm/CNRS/Université Claude Bernard Lyon 1/Université Jean-Monnet-Saint-Etienne), University College London, University of Liège and University of Geneva, looked at the potential physiological, cognitive, and emotional benefit of meditation in elderly individuals.

In the Age-Well clinical trial involving 136 participants aged 65 or older with no known diseases, the researchers measured the impact of an 18-month meditation intervention on tissue volume and perfusion (physiological process of supplying an organ with nutrients and oxygen necessary for its metabolism) of the insula and anterior cingulate cortex. They also looked at specific cognitive and socio-affective parameters.

The participants were assigned to three groups in order to compare the potential benefit of meditation with different types of interventions. The first group followed the meditation intervention protocol (mindfulness meditation and loving kindness and compassion meditation), the second group (the “active control” group) followed a period of English-language training, and the third group (the “passive control” group) did not follow any intervention.

After 18 months of intervention, the researchers saw no significant changes in volume or perfusion of the cingulate cortex or insula in the meditation group compared to the control groups.

“The fact that no anatomical differences were observed between these two groups could indicate that while meditation can modify the volume of younger and more plastic brains, 18 months of meditation training are not enough to modify the effects of aging,” analyzes Chételat. “In addition, while the results of the volume measurement are strictly negative, those of the perfusion show a trend in favor of meditation that could be interesting to explore over a longer intervention time and/or with a larger population sample,” specifies the researcher.

The research team will therefore conduct a 4-year follow-up of the participants, to investigate potential long-term effects.

In contrast, significant differences were observed in behavioral measures between the meditation group and the English-learning group, with improved regulation of attention and socio-emotional capacities in the meditation group participants. “Here the practice of meditation is showing its real benefit on the mental health of elderly people, with a significant improvement in parameters specific to well-being and fulfilment, but also to the maintenance of attentional and socio-emotional capacities, as reported by participants,” adds Antoine Lutz, responsible for the study’s meditation component.

More specific measurements and analyses will be conducted within the Age-Well trial to improve the understanding of these mechanisms. These analyses could be used to identify the measures which are most sensitive to meditation and to study the mechanisms behind its effects.

Some GnRH neurons (green) express NOS1 (red) during their migration from the nose to the brain during fetal life. The GnRH + NOS1 double-labeled cells appear in yellow. © Vincent Prévot/Inserm

Children born prematurely have a higher risk of not just cognitive and sensory disorders, but also infertility in adulthood. In a new study, a team of researchers from Inserm, University Hospital Lille and Université de Lille at the Lille Neuroscience and Cognition laboratory has opened up interesting avenues for improving their prognosis. By conducting research into a rare disease known as congenital hypogonadotropic hypogonadism, the scientists have discovered the key role of an enzyme and the therapeutic potential of the neurotransmitter that it synthesizes – nitric oxide – in reducing the risk of long-term complications in the event of prematurity. Their findings are described in Science Translational Medicine.

Congenital hypogonadotropic hypogonadism is a rare disease characterized by delayed puberty or the complete absence of puberty in adolescence, leading to infertility. Some forms of the disease are caused by a lack of production of GnRH, a hormone produced in the brain that remotely controls the development and functioning of male and female gonads through various intermediaries.

The team of Vincent Prévot, Inserm Research Director, specializes in the dialogues between the brain and the rest of the body.

Here the scientists looked at nitric oxide, a neurotransmitter that regulates the activity of GnRH neurons, and more specifically NOS1, the enzyme that synthesizes it.

“Nitric oxide suppresses the electrical activity of the GnRH neurons and modulates the release of this hormone, so NOS1 dysfunction was not ruled out as being the cause of congenital hypogonadotropic hypogonadism,” explains Prévot, the principal coordinator of the study.

To go further, his team collaborated with a laboratory in Lausanne (Switzerland) which has a cohort of 341 patients with this disease. Using DNA samples, they looked for the presence of rare mutations on the gene encoding the NOS1 enzyme and found five different mutations that could explain the disease. Some of the individuals concerned had, in addition to fertility problems, sensory and cognitive disorders (intellectual disability or loss of hearing or smell).

An application in the context of preterm birth?

The next stage of the study consisted of developing a NOS1-deficient mouse model[1] in order to better understand the role of this enzyme. The researchers encountered puberty problems, as well as sensory and neurological alterations, as observed in humans with congenital hypogonadotropic hypogonadism. They also saw an exacerbation of minipuberty in these animals. Minipuberty occurs in all mammals just after birth (between one and three months of age in humans) and triggers an initial brain activation of the axis controlling reproduction prior to the “real” puberty in adolescence.

Here the researchers observed that the peak of the sex hormone associated with this minipuberty was twice as high in NOS1-deficient mice.

“This caught our attention because premature infants also tend to present a more intense minipuberty than usual. And the greater the prematurity, the greater the risk of neurosensory and mental complications in adulthood,” reiterates Konstantina Chachlaki, Inserm researcher and first author of the study.

Based on these observations, the researchers tested the administration of nitric oxide in NOS1-deficient mice just after their birth, during the minipuberty period. What they saw was the reversal of all the symptoms they had developed: the puberty problems and sensory and neurological disorders disappeared, and this was over the long term, for the remainder of their lives.

An ongoing clinical trial

These promising findings could help to improve the care of preterm infants. Nitric oxide is also given to some children born prematurely, to facilitate the opening of the bronchi in the event of breathing difficulties.

“In light of this consistency of observations and practices, we decided to set up a clinical trial to test the effect of nitric oxide in preterm infants by studying reproductive and neurosensory parameters,” explain Prévot and Chachlaki, who are coordinating a European project dedicated to…“Administering nitric oxide at birth could reduce the risk of reproductive, sensory and intellectual complications in children born prematurely. This is what we are going to try to verify in the wake of these astonishing discoveries in mice,” they continue.

The miniNO trial was launched at University Hospital Lille in partnership with a hospital in Athens (Greece). The objective is to verify whether children receiving this treatment go on to experience normal minipuberty and puberty, and whether they develop fewer sensory and neurological complications compared to premature infants who were not administered nitric oxide at birth.

[1] In which the gene encoding the NOS1 enzyme was disactivated.