Dementia Breakthrough: Brain Scans Predict Disease Up to 9 Years Early

Diagnosing dementia early gives us more time to put precautions in place and to study exactly how the condition progresses – and a new method for predicting conditions such as Alzheimer's disease is promising up to nine years of advance warning.

The method, developed by a team from the Queen Mary University of London in the UK and Monash University in Australia, involves a neurobiological model that analyzes brain scans captured by functional magnetic resonance imaging, or fMRI.

In tests, the model was more than 80 percent accurate at predicting the development of dementia. That has huge potential in terms of early diagnosis, and it also addresses another challenge: the large number of people with dementia who don't get diagnosed at all.

"Predicting who is going to get dementia in the future will be vital for developing treatments that can prevent the irreversible loss of brain cells that causes the symptoms of dementia," says neurologist Charles Marshall, from the Queen Mary University of London.

Specifically, the team looked at a key part of the brain's system, called the default mode network (DMN). It's the first part of the brain to be affected by damage caused by Alzheimer's disease, the most common form of dementia, and it plays a key role in connecting up different parts of the brain to keep our thoughts in order.

The test included brain scans of 81 individuals, who were undiagnosed at the time but who later went on to develop dementia, as well as 1,030 matched controls. Using their model, the team was able to spot signs of dementia in some brains up to nine years ahead of time. The fMRI scans are easy to administer, and only take a few minutes to complete.

As well as hitting that 80 percent accuracy rate, the technique could also predict when a dementia diagnosis would be made, within a two-year margin. This is all hugely useful information, and can be cross-referenced against other known risk factors for dementia to build up a better picture of who this disease affects and how it emerges.

"Using these analysis techniques with large datasets we can identify those at high dementia risk, and also learn which environmental risk factors pushed these people into a high-risk zone," says neurologist Samuel Ereira, from the Queen Mary University of London.

The researchers also linked risk factors for Alzheimer's, such as genetics and social isolation, to changes in DMN connectivity. Knowing what triggers these neurobiological conditions is going to be vital in the search for a cure.

Another scenario where the analysis technique is going to be helpful will be in the study of people whose brains show signs of dementia, but who develop symptoms much later on. Understanding why this happens should teach us more about how the condition progresses and how it might be slowed down.

"We hope that the measure of brain function that we have developed will allow us to be much more precise about whether someone is actually going to develop dementia, and how soon, so that we can identify whether they might benefit from future treatments," says Marshall.

The research has been published in Nature Mental Health.

 

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Transcendental meditation correlated with specific changes in the brain

A new study conducted at IMT School for Advanced Studies Lucca shows that the subjective feeling of well-being experienced by many people with the practice of meditation is correlated with specific changes in the brain.

The research, which appeared in Brain and Cognition, examined the effects of the technique known as Transcendental Meditation (TM), which consists in the silent repetition of a meaningless sound, a "mantra".

For the study, conducted at the Molecular Mind Laboratory (MoMiLab) of IMT School for Advanced Studies Lucca, the researchers enrolled 34 healthy young volunteers and divided them in two groups. The first one practiced Transcendental Meditation 40 minutes per day in two sessions of 20 minutes each, one in the morning and the other in the evening; the second group did not change its daily routine.

At the beginning of the study, the researchers also measured through psychometric questionnaires the anxiety and stress level of all the participants, as well as their ability to manage stressful situations. Each individual was also subjected to a functional magnetic resonance imaging test (fMRI), in order to measure brain activity at rest and changes in the functional connectivity among different cerebral areas. After three months, at the end of the study, the same tests were repeated.

The analysis of the data clearly showed that levels of anxiety and stress perceived by the subjects who followed the meditation program were significantly reduced in comparison with those of the volunteers who did not practice TM.

Magnetic resonance imaging also shows that the reduction of anxiety levels is associated with specific changes in the connectivity between different cerebral areas, such as precuneus, left parietal lobe and insula, which all have an important role in the modulation of emotions and inner states. In the control group, instead, none of these changes was observed".    Giulia Avvenuti, Ph.D. fellow at IMT School and first author of the study.

"The fact that Transcendental Meditation has measurable effects on the 'dialogue' between brain structures involved in the modulation of affective states opens new perspectives for the understanding of brain-mind relationships" says Pietro Pietrini, IMT School's Director and coordinator of the study. "It also extends the results of recent research suggesting that drugs therapies and psychotherapy leverage on the same biological mechanism".

Transcendental Meditation has recently gained an increasing success worldwide as a relaxation practice also thanks to the David Lynch Foundation, which co-financed the study along with the Fondazione Cassa di Risparmio di Lucca. Founded in 2005 by the movie director David Lynch, who is himself a longtime practitioner and supporter of the social value of Transcendental Meditation, the David Lynch Foundation promotes TM practice as an approach to reduce stress in schools (as for the 'Quiet Time-Meditate Lucca' project at the Pertini High School) and workplaces, and to build resilience in victims of trauma.

"I am very happy of the results of this study that used the latest technology to show the beautiful benefits for the human beings of TM. Now I'm working to form my foundation also in Italy, with teachers who teach transcendental meditation in schools, work places and other groups, reaching as many people as possible" says David Lynch.

This new study, coherently with previous ones, shows that even a few months of practice of Transcendental Meditation have positive effects on psychological well-being and that these effects are correlated with measurable changes in the brain.

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Prenatal stress changes brain connectivity in-utero

The time babies spend in the womb is far from idle. The brain is changing more rapidly during this time than at any other time in development. It is an active time for the fetus to grow and explore, and of course connect to its mother. And new evidence from in-utero fetal brain scans shows, for the first time, that this connection directly affects brain development: A mother's stress during pregnancy changes neural connectivity in the brain of her unborn child.

"It has long been thought that the stress of a mother during her pregnancy may imprint on the brain of her developing child," says the author who is presenting this new work today. "Despite the clear importance of this time frame, we presently possess very little understanding of how functional macroscale neural networks build during this precious time in human life, or the relevance of this to future human health and development."

This prenatal work is part of a growing body of research to better understand how the human brain develops across its lifespan, from fetus to old age. "We are interested in how a human brain constructs over time to become the adult brain," says the author whose work focuses on identifying sensitive periods of brain development from childhood into adolescence. She is chairing a session on new findings in brain development at the meeting: "The talks aim to bridge across the very long brain development that gives rise to mature functioning."

Seeing the changing fetal brain
Research in newborns and older children to understand prenatal influences has been confounded by the postnatal environment, the Dr. explains. But recent advancements in fetal imaging allowed her and her team to gain insight into a critical time period in brain development never previously accessible.

Using fetal resting-state fMRI, they examined functional connectivity in 47 human fetuses scanned between the 30th and 37th week of gestation. The researchers recruited the participating mothers from a low-resource and high-stress urban setting, with many reporting high-levels of depression, anxiety, worry, and stress.

They found that mothers reporting high stress had fetuses with a reduced efficiency in how their neural functional systems are organized. It is the first time, imaging has shown a direct influence of maternal stress on fetal brain development, independent of influences of the postnatal environment.
"The major thrill is that we have demonstrated what has long been theorized, but not yet observed in a human, which is that the stress of a mother during her pregnancy is reflected in connectional properties of her child's developing brain," the Dr. says. The data suggest that the brain does not develop in a sequence from simplest systems (e.g., vision, motor) to more complex high-order systems, but perhaps instead first develops the areas that will be most critical in bridging across systems.

The researchers found that the cerebellum played a central role in the observed effects, suggesting it may be especially vulnerable to the effects of prenatal or early life stress. The cerebellum has the highest density of glucocorticoid receptors, which are involved in stress responses, than any other place in the brain. The Dr. and her team plan to further investigate this as a possible mechanism for the stress responses they observed.

Although conducting in-utero brain scans are challenging -- first and foremost because of the always wriggling babies -- working with expectant mothers is quite rewarding, the Dr. says. "A lot of our moms are interested in being part of this research, not because of concerns they have in their pregnancy," she says, "but because they appreciate the heightened vulnerability of budding human life, and this is an opportunity to help other women that may not have the same fortune in their circumstances."

Making connections into adulthood
Cognitive neuroscientists are especially interested in understanding sensitive periods of time when the environment has the largest influence on future brain functions. To identify such times, the team has honed in on connections between the prefrontal cortex (PFC) and the amygdala.

"A majority of developmental change during childhood and adolescence are the changes in connections," she explains. "We have largely focused on the connections between the amygdala and prefrontal cortex because of the very large changes we have observed there across childhood and adolescence and their central role in emotional behaviors."

Studying awake children as young as 4-years old, the researchers identified developmental periods when the nature of the communication between the amygdala and the PFC operates differently than in an adult. The connections develop very slowly over childhood, with a dramatic shift toward the end of childhood when the transition to adolescence brings about more adult-like characteristics. Looking at coincidental environmental events in childhood, the researchers also found data to suggest that amygdala-medial PFC connections are highly impressionable to external forces.

"The human brain is designed to learn from the environment. This is thanks to the long period of infancy, childhood, and adolescence that humans enjoy," the Dr. says. "What has amazed me most about the developing brain is that it is not simply an immature version of the adult brain but instead is designed to collaborate with the expected care-giving ecology."

Indeed, says the Dr.: "We must consider the developing brain in context, thinking about the role of the environment in shaping the brain. It is a topic that inspires us to promote healthy brain growth, to ask what it is that we do for children in the lifestyles, opportunities, and learning conditions we create for them."

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Study suggests stress a common seizure trigger in epilepsy

Patients of epilepsy, Beware! Too much stress can be really harmful for you.
 
According to a recent study, stress has come out as the most commonly reported triggers for seizures. The study was published in the journal Seizure.

The research looks at the stress-seizure relationship and how adopting stress reduction techniques may provide benefit as a low risk form of treatment.

The relationship between stress and seizures has been well documented over the last 50 years. It has been noted that stress can not only increase seizure susceptibility and in rare cases a form of reflex epilepsy, but also increase the risk of the development of epilepsy, especially when stressors are severe, prolonged, or experienced early in life.

"Studies to date have looked at the relationship from many angles. The earliest studies from the 1980s were primarily diaries of patients who described experiencing more seizures on high-stress days than on low-stress days," said Michael Privitera, MD, director of the UC Epilepsy Center and professor in the Department of Neurology and Rehabilitation Medicine at the UC College of Medicine.

Privitera and Heather McKee, MD, an assistant professor in the Department of Neurology and Rehabilitation Medicine, looked at 21 studies from the 1980s to present--from patients who kept diaries of stress levels and correlation of seizure frequency, to tracking seizures after major life events, to fMRI studies that looked at responses to stressful verbal/auditory stimuli.

Most all [of these studies] show increases in seizure frequency after high-stress events. Studies have also followed populations who have collectively experienced stressful events, such as the effects of war, trauma or natural disaster, or the death of a loved one," added Privitera.

All of which found increased seizure risk during such a time of stress. For example, a study conducted in 2002 evaluated the occurrence of epileptic seizures during the war in Croatia in the early 1990s.

Children from war-affected areas had epileptic seizures more often than children not affected by the war. Additionally, the ten year follow up showed that patients who had their first epileptic seizure during a time of stress were more likely to have controlled epilepsy or even be off medication years later.

"Stress is a subjective and highly individualized state of mental or emotional strain. Although it's quite clear that stress is an important and common seizure precipitant, it remains difficult to obtain objective conclusions about a direct causal factor for individual epilepsy patients," says McKee.

The researchers suggest patients who believe stress is a seizure trigger may want to talk with their health care provider about screening for anxiety.

"Any patient reporting stress as a seizure trigger should be screened for a treatable mood disorder, especially considering that mood disorders are so common within this population," adds McKee.

The researchers report that while some small prospective trials using general stress reduction methods have shown promise in improving outcomes in people with epilepsy, large-scale, randomized, controlled trials are needed to convince both patients and providers that stress reduction methods should be standard adjunctive treatments for people with epilepsy.

"What I think some of these studies point to is that efforts toward stress reduction techniques, though somewhat inconsistent, have shown promise in reducing seizure frequency. We need future research to establish evidence-based treatments and clarify biological mechanisms of the stress-seizure relationship," says Privitera.

Overall, he says, recommending stress reduction methods to patients with epilepsy "could improve overall quality of life and reduce seizure frequency at little to no risk." Some low risk stress reduction techniques may include controlled deep breathing, relaxation or mindfulness therapy, as well as exercise, or establishing routines.

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