Points of View
Sleep well to age well
By Dr Géraldine Rauchs
(posted 5th June 2018)
Sleep is an essential part of our lives. Its functions are multiple, including brain development during the first years of life, growth hormone secretion, memory consolidation and for the efficient functioning of our immune systems. Recent studies have suggested that sleep may also contribute to the elimination of waste products that accumulate in the brain during the day, notably the amyloid-beta peptide that is commonly associated with Alzheimer’s disease. If this is the case, poor sleep quality may increase the risk of this debilitating disease.
At the Inserm laboratory in Caen, we have spent almost five years exploring sleep quality in older adults. To do so, we have used a range of complementary tools: sleep questionnaires, actigraphy (the recording of a person’s movements over several days to provide information about activity-rest cycles) and polysomnography (the use of electrodes placed over the head to monitor sleep). The sleep measures obtained are combined with advanced neuroimaging techniques, including Magnetic Resonance Imaging (MRI) to measure the volume of the brain, and Positron Emission Tomography (PET) to measure its functioning or to visualize amyloid deposits, one of the typical lesions of Alzheimer’s disease.
Firstly, we have found that seniors who complain of recurring difficulties falling asleep present greater amyloid deposits than individuals who easily fall into the arms of Morpheus. In addition, people who frequently awaken during the night also have lower grey matter volume in a small brain area named the insula, involved in the generation of some sleep rhythms. These results were obtained from sleep questionnaires, but preliminary analyses using more objective sleep indicators confirm that poor sleep quality is associated with greater brain alterations and lower cognitive performance. At first sight, these results may appear particularly alarming. But it is important to keep in mind that we can improve our sleep quality without taking sleeping pills. For instance, exposure to bright light during the day and physical activity can be effective ways to improve sleep.
In the Silver Santé Study, part of our work aims to identify lifestyle factors that may either curb or accelerate the rate of cognitive decline as we age. Among these factors, we are increasingly convinced that sleep may be an important factor to screen in order to prevent cognitive decline and reduce the risk of Alzheimer’s disease. We also suspect that brain training activities such as meditation and foreign language-learning may help to improve sleep quality and to maintain optimum brain structure and function so we look forward to learning more about this and to sharing our results towards the end of the Silver Santé Study.
André C, Tomadesso C, Mézenge F, Branger P, De Flores R, Eustache F, Chételat G, Rauchs G. (2017). Age-related NREM-sleep fragmentation: relationships with structural and metabolic brain alterations, amyloid burden and cognitive performance. Alzheimer’s Association International Conference (July 16-20 2017, London, UK).
Branger P, Arenaza-Urquijo EM, Tomadesso C, Mézenge F, André C, de Flores R, Mutlu J, de La Sayette V, Eustache F, Chételat G, Rauchs G. (2016). Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood. Neurobiol Aging, 41:107-114. doi: 10.1016/j.neurobiolaging.2016.02.009.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156):373-7. doi: 10.1126/science.1241224.
A year of learning through the eyes of instructors
By Caitlin Ware
(posted 29th March 2018)
Silver Santé is studying the impact of mental training techniques, such as meditation practice or language learning, on people in later life. A year ago, volunteers in the first wave of the Age Well Study in Caen, France, were randomly assigned to a group practicing one of these activities. During this time, their instructors have witnessed the participants’ motivation, enjoyment, and personal growth.
Several of the instructors have been impressed by how motivated the volunteers appear to be.
Meditation instructor, Titi Tran, said: “All of the participants are very motivated to apply what they’ve learned to their own meditation practice; they’re able to integrate what they learn in class and apply it to themselves.”
English instructor Corinne Schimmer also commented on the participants’ dedication and motivation: She said: “I would probably say that one of the most striking aspects is the high motivation in the group, and that it has increased as the months have passed.
“The volunteers mention that despite the fact that they are supposed to work for about 20 minutes per day, most of them work for much longer than that. Some people say that once they’ve started they can’t really stop working – not because there is an exam at the end of the course, but really because they seem to be enjoying it.”
Indeed, enjoyment seems to play a big part in their motivation: “Some of them enjoy learning English because they want to be able to travel, or talk with friends,” noted Corrine. “I think they actually enjoy the process of learning English in itself.”
As participants were randomly assigned to the meditation or English interventions, they were not always placed in their preferred group. However, most participants quickly came to appreciate their designated class: “Two or three participants would have preferred to learn English, but they were also happy to practice meditation. Now they’re used to it,” said Martine Bachelor, meditation instructor who also stressed the importance of group cohesion. She said: “From our perspective, we rapidly observe the effects of belonging to a group; the participants listen to one another and get to know each other.”
Corinne also highlighted the social dimension saying: “I think that the volunteers will miss coming to the classes once the study is over, and probably not only for the learning process, but for the social aspect.” Similarly, Titi remarked: “Now that it’s been 12 months, they are starting to think about when the experiment will be over and I think they are already a bit sad that it’s ending.”
Finally, the instructors have mentioned the positive impact of the study on their teaching. Corinne concluded: “I also find it very invigorating to review my teaching techniques in this context; it makes me have a look at the learning process in a completely different kind of way. So all in all it’s a very good experience for me as a teacher as well.”
Responsibility in the Silver Santé Study means caring for others
By Mareike Smolka
(posted 11th December 2017)
As scientific research and technology development increasingly influence everyday life, responsibility emerges as a theme of discussion. Often related to using science for the benefit of society, engaging in risk management or adhering to principles of good scientific practice, it is a concept with multiple meanings. This article outlines what responsibility means for scientists in the Silver Santé Study.
The Silver Santé Study is funded by the EU Horizon 2020 Research and Innovation programme, which supports projects promoting so-called “Responsible Research and Innovation” (RRI). RRI has become a key word in academia and policy-making since the beginning of the 21st century; however, the concept still lacks clarity and definition. It is an umbrella term allowing for multiple interpretations, especially because the notion of responsibility has a long history in science. Concerns about responsible research arose when physicists worried about the dual use of nuclear fission for both civil and military purposes prior to the production of the atomic bomb. The notion of responsibility entered neuroscience in the 1970s; back then, the Society for Neuroscience created a Committee on Social Responsibility organising roundtable discussions on socially sensitive topics.
What does responsibility mean to neuroscientists involved in the Silver Santé Study? What do they contribute to define and realise RRI? To answer these questions, I visited the research institute Cyceron in Caen, France, where the Silver Santé Study is based and conducted interviews with key researchers. My results suggest that responsibility in the Silver Santé Study takes on a relational character. What neuroscientists feel responsible for depends on who they feel responsible to. Neuroscientists particularly emphasise their responsibilities to research participants and fellow researchers.
The Project Coordinator Dr Gaël Chételat points out that responsible research goes beyond protecting research participants from physical or mental harm and safeguarding their privacy as required by research regulation. She stresses that researchers have the responsibility to engage in respectful and friendly relationships with research participants and, therefore, encourages her team to turn research participation into a “nice experience”. Her team members take this very seriously when taking physiological and behavioural measurements: attentively covering research participants with blankets to ensure that they feel comfortable in the brain scanner, explaining experimental tasks with patience, encouraging participants to share their experiences, and showing curiosity for their personal stories.
According to neuroscientist Dr Olga Klimecki of the University of Geneva, the Silver Santé Study represents a “good example of responsibility in team work and collaboration”. Dr Klimecki, who investigates the impact of emotions on mental health as part of the study, takes the view that scientists ought to uphold two central responsibilities to their fellow researchers: crediting authorship of scientific articles and supporting maternity. She appreciates that the researchers involved in the Silver Santé Study make efforts to take on both responsibilities. Dr Antoine Lutz, who is based at the Lyon Neuroscience Research Centre and manages the project’s meditation intervention, deems researchers responsible for creating a cooperative working atmosphere. He acknowledges that this is realised in the Silver Santé Study by means of a horizontal hierarchy; “it is not a regular pyramid with an alpha male”.
Exploring what responsibility means in the Silver Santé Study reveals how responsibilities are adopted by researchers in daily routine and shape their concrete interactions with others. Maintaining and fostering these already existing responsibilities might contribute to the definition and implementation of RRI. It remains open for interpretation why particular emphasis is placed on relational responsibilities in the Silver Santé Study – responsibilities neuroscientists feel to others. Dr Lutz offers one possible explanation: “In general, whoever is involved in the study, I think they also try to embody some of the qualities that we are studying”. Accordingly, both the practice and study of meditation seem to promote responsibility as caring for others.
Chételat, G. (April 25, 2017). Personal communication on responsible research in the Silver Santé Study. Interview conducted at the biomedical research institute Cyceron in Caen, France.
European Commission (2014). Clinical Trials Regulation (EU) No 536/2014. Retrieved on May 8, 2017, from http://ec.europa.eu/health/sites/health/files/files/eudralex/vol- 1/reg_2014_536/reg_2014_536_en.pdf
Klimecki, O. (April 27, 2017). Personal communication on responsible research in the Silver Santé Study. Interview conducted via telephone.
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Stahl, B. C. (2013). Responsible research and innovation: The role of privacy in an emerging framework, Science and Public Policy, 40, 708-716.
Tancoigne, E., Randles, S., & Joly, P. (2016). Small and Divided Worlds. A Systematic Review and Scientometric Analysis of RRI Literature. In R. Lindner, S. Kuhlmann, S. Randles, B. Bedsted, G. Gorgoni, E. Griessler, . . . N. Mejlgaard (Eds.): Navigating Towards Shared Responsibility in Research and Innovation. Approach, Process and Results of the Res-AGorA Project (pp. 39-44). Karlsruhe: Fraunhofer ISI.
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What is a memory clinic?
By Frank Jessen
(posted 25th September 2017)
Memory clinics are interdisciplinary special services, which offer a detailed work-up of memory problems in people in later life. Usually, patients are referred to memory clinics by their primary care physician, psychiatrist or neurologist and it is at the memory clinic that patients provide a history of their memory problems, which is ideally supported by a spouse or caregiver.
The next step is to perform a cognitive test. These tests are standardized measures of memory, language abilities, attention and other domains, which are used to determine whether a patient has a cognitive capacity within the age-expected age range or below. This is often followed by blood examinations to detect any medical conditions, which may cause memory problems – for example, hypothyroidism. Also, a brain magnetic resonance imaging (MRI) scan is usually obtained to identify brain lesions, such as infarcts or tumors, which can also cause memory disturbances. In some centres, advanced technologies such as positon emission tomography (PET – which show the molecular aspects of the brain), are also provided. Most memory clinics offer examination of the cerebrospinal fluid (CSF) which can identify Alzheimer’s disease (AD) related changes of protein concentrations, allowing the diagnosis of AD with high certainty.
Memory clinics usually offer a variety of treatment options. These include counselling and non-pharmacological interventions, such as cognitive training or occupational therapy as well as caregiver support groups. Memory clinics also assess the need for pharmacological anti-dementia treatment and sometimes provide the medication directly. Many memory clinics also offer patients the chance to participate in clinical trials with novel pharmacological and non-pharmacological therapies. The focus of these trials is usually very early treatment or prevention of dementia in AD. The Silver Santé Study provides an excellent example of the role memory clinics play in clinical trials. At the Clinic for Psychiatry and Psychotherapy at the University Hospital Cologne, where I am director, patients are currently taking part one of the Study’s trials to assess the effect of short-term interventions, such as on behavioural measures. Each patient has some level of subjective cognitive decline, so their improvement can be measured along with the intervention. Behavioural measures will be monitored to see how much of a difference can be made to participants’ well-being due to the intervention.
Memory clinics provide dementia diagnosis and treatment at an expert level and are a key component of up-to-date dementia care. The more refined future dementia treatment becomes, the more central the role of memory clinics for patients and professionals will be. We hope that the results of the Silver Santé Study can feed into that refinement and help enhance and improve how we all safeguard our mental health and well-being in later life.
Emotions and their lasting impact on the brain
By Sebastian Baez, Ph.D. Candidate
(posted 27th March 2017)
As medical advances allow people to live longer, it’s becoming increasingly important that we take care of our mental health as well as our physical health in later life. As we get older, our bodies, brains and minds age too, carrying with them some changes that are welcome, but others that are more challenging. Emotional-related changes, for example, are an important component of psychological health and well-being in older adults.
Emotions and their control are central aspects of everyday life. Not only do they influence our daily moods, but the emotional impact of a given experience can motivate behaviours, alter memories, change our sense of morality, and even bias reasoning and decision making. Emotional changes throughout life are indeed necessary for developing new skills. But if not managed properly, they can – in some cases – be linked to negative experiences of psychological distress, anxiety, and even depressive episodes.
I am part of a team at the University of Geneva, working solely on the Silver Santé Study, which is exploring the impact emotions have on the brain, how mental training techniques influence emotional well-being, and what benefits this may bring to us all in later life.
In order to study emotional processes in the human brain, we use neuroimaging methods such as functional Magnetic Resonance Imaging (fMRI). In this method, the magnetic properties of blood can be used to localise changes in brain activity while participants are lying in an MRI scanner. By asking them to perform certain tasks or to rest, we can measure which brain activation patterns are generated in a given task or in the resting state.
Recent discoveries about the emotional areas of the brain have allowed us to study how emotions are represented there, as well as how they may be controlled, heightened or reduced. There is also a growing interest in understanding how emotions unfold over time and for how long we can measure their effects on the brain and on various cognitive functions such as attention, reasoning, or memory. Previous studies have shown that emotions can have a lasting effect after an emotional episode. Researchers consider that some affective states may be resistant to change once they have been triggered, and that the duration of this carry-over depends on individual coping abilities and personality factors. The critical point is that a stronger and longer impact of emotions on the brain and cognition has been associated with higher levels of anxiety, rumination, and risk for depression.
Moreover, some recent fMRI studies have discovered that short emotional episodes can produce effects on brain activity and brain connectivity that are long-lasting in that they continue during a resting period several minutes after the actual emotional event. Furthermore, recent research on people suffering from depression has shown that by measuring brain activity at rest it is now possible to distinguish between different subtypes of depression.
Our team strongly believes that mental training techniques are a great tool to successfully regulate negative emotional experiences. Mental training might help facing high emotional encounters and even impact on emotional experiences and cognitive changes triggered by emotions, thereby contributing to the well-being of elderly people.
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Can healthy lifestyle choices help prevent dementia?
By Dr Eider M Arenaza-Urquijo
(posted 16th December 2016)
There is now much evidence to support the idea that healthy lifestyle choices may play an important role in the prevention of Alzheimer’s disease. Studies show that keeping mentally and physically active may offer protection against developing cognitive decline and dementia.
For almost four years, we have been using advanced neuroimaging techniques in our Caen laboratory in order to understand how lifespan mental and physical activities influence our brain, notably in later life. We have used magnetic resonance imaging (MRI) to measure the volume, structure and neural activity of the brain and positron emission tomography (PET), a technique that allows measuring the metabolic activity of the brain.
Several neuroimaging studies point to the idea that mental and physical activities throughout life are related to preserved brain structure and function in later life. In our laboratory, we have studied the brains of a group of people aged between 60 and 80 years old in relation to the number of years they attended school (as an indicator of mental activity early in life). Participants who spent longer at school had more preserved brain tissues, elevated metabolic function and stronger connections between different brain regions. These regions included the hippocampus and the frontal lobe – both especially vulnerable to ageing and Alzheimer’s disease processes. The stronger connections between these areas sustained better performances in functions such as memory or attention in participants who spent longer at school.
So is it ever too late to adopt healthy lifestyle habits? A recent review that collected and analyzed multiple research studies indicates that even making changes later in life could reduce the risk of developing Alzheimer’s disease. In line with this idea, we recently showed that older adults (60-90 years) who are currently more frequently engaged in mental or physical activities – such as reading or playing games, walking or gardening – had larger hippocampal and frontal regions. Notably, both kinds of activities seem to have a positive effect on these brain structures in a complementary way.
Unfortunately, having a healthy lifestyle does not necessarily prevent you from developing Alzheimer’s disease. The development of dementia is a complex process that involves several factors, such as genetics, lifestyle and environment. Studies, however, suggest that positive lifestyle factors may counteract the harmful deleterious effects of genes. In a recent study we observed that people carrying the highest known genetic risk for Alzheimer’s disease but who were highly cognitively engaged, had elevated metabolic function in some brain areas relating to memory performance. Moreover, when Alzheimer’s disease pathology is present in the brain, the brains of individuals with a higher engagement in cognitive and physical activities might be better equipped to compensate for the pathology, meaning that the onset of the symptoms might be delayed.
As part of the Silver Santé Study, we are translating all this promising evidence into a mental training program for adults aged 65 years or older, who will take part in the study for 18 months. This will allow us to observe how their brain structure and function change in response to training. We hope this will provide us with a better understanding of the mechanisms underlying mental activity in later life and how that relates to brain and cognitive health.
Arenaza-Urquijo et al., Neuroimage, 2013 https://www.ncbi.nlm.nih.gov/pubmed/23796547
Arenaza-Urquijo, de Flores et al., Brain Imaging and Behavior, 2016 https://www.ncbi.nlm.nih.gov/pubmed/27757821
Arenaza-Urquijo et al., Neurology, 2015 https://www.ncbi.nlm.nih.gov/pubmed/26408498
Arenaza-Urquijo et al., Frontiers in Aging Neuroscience, 2015 https://www.ncbi.nlm.nih.gov/pubmed/26321944