Improved Detection of Frontotemporal Degeneration May Aid Clinical Trial Efforts

A series of studies demonstrate improved detection of the second most common form of dementia, providing diagnostic specificity that clears the way for refined clinical trials testing targeted treatments. The new research is being presented by experts from the Perelman School of Medicine at the University of Pennsylvania at the American Academy of Neurology’s 65th Annual Meeting in San Diego March 16-23, 2013.

Frontotemporal degeneration, the most common dementia in people under 60, can be hereditary or sporadic in nature and caused by one of two different mutated proteins (tau or TDP-43). The disease results in damage to the anterior temporal and/or frontal lobes of the brain. As the disease progresses, it becomes increasingly difficult for people to plan or organize activities, behave appropriately in social or work settings, interact with others, and care for oneself, resulting in increasing dependency.

In one study, the team confirmed that a novel multimodal imaging approach was more accurate (88 percent) than using either MRI (72 percent) or DTI (81 percent) alone to detect FTD versus Alzheimer’s disease. The two imaging techniques integrate measures of white matter and grey matter, providing a statistically powerful method for predicting underlying pathology in order to screen patients for clinical trials.

“We are moving forward on our biomarker work to optimize our ability to identify the specific cause of an individual’s difficulties during life, said senior author Murray Grossman, MD, EdD, professor of Neurology and director of the Penn FTLD Center. “We use a novel multi-modality approach involving behavioral, imaging and biofluid biomarker measures.”

In a second study, researchers found that a brief series of neuropsychological tests of memory, word generation and conceptual flexibility (needed for creative problem-solving) helped differentiate people with very mild behavioral variant FTD (bvFTD) and those with mild cognitive impairment (MCI). The combination of tests correctly classified 85.7 percent of bvFTD cases and 83.3 percent of MCI cases at early stages of disease.

“This is particularly important because treatment trials with disease-modifying agents are emerging, often based on animal studies, yet we still don’t have all the tools we need to identify who is most appropriate to participate in one of these trials. Moreover, we can use this information we ascertain to help determine who is responding to a treatment in a clinical trial.” 

The third study being presented at the meeting showed that hereditary forms of FTD appear to have more rapid cognitive decline and differing tau profiles compared with sporadic forms of the disease. For clinical trials testing whether a drug can delay damage caused by tau, any known differences in the speed of disease progression could interfere with trial results.

(Image courtesy: University of Pennsylvania)

New MRI method fingerprints tissues and diseases

A new method of magnetic resonance imaging (MRI) could routinely spot specific cancers, multiple sclerosis, heart disease and other maladies early, when they’re most treatable, researchers at Case Western Reserve University and University Hospitals (UH) Case Medical Center suggest in the journal Nature.

Each body tissue and disease has a unique fingerprint that can be used to quickly diagnose problems, the scientists say.

By using new MRI technologies to scan for different physical properties simultaneously, the team differentiated white matter from gray matter from cerebrospinal fluid in the brain in about 12 seconds, with the promise of doing this much faster in the near future.

The technology has the potential to make an MRI scan standard procedure in annual check-ups, the authors believe. A full-body scan lasting just minutes would provide far more information and require no radiologist to interpret the data, making diagnostics cheap, compared to today’s scans, they contend.

"The overall goal is to specifically identify individual tissues and diseases, to hopefully see things and quantify things before they become a problem," said Mark Griswold, a radiology professor at Case Western Reserve School of Medicine and UH Case Medical Center. "But to try to get there, we’ve had to give up everything we knew about the MRI and start over."

Griswold has been working on this goal with Case Western Reserve’s Vikas Gulani, MD, an assistant professor of radiology, and Nicole Seiberlich, assistant professor of biomedical engineering, for a decade. During the last three years, they developed the technology and proved the concept with graduate student Dan Ma; Kecheng Liu, PhD, collaborations manager from Siemens Medical Solutions Inc.; Jeffrey L. Sunshine, MD, professor of radiology and a radiologist at UH Case Medical Center; and Jeffrey L. Duerk, dean of Case School of Engineering and professor of biomedical engineering.

(Image: Rex Features)

Veterans with mild traumatic brain injury have brain abnormalities

Mild traumatic brain injury (TBI), including concussion, is one of the most common types of neurological disorder, affecting approximately 1.3 million Americans annually.

It has received more attention recently because of its frequency and impact among two groups of patients: professional athletes, especially football players; and soldiers returning from mid-east conflicts with blast-related TBI. An estimated 10 to 20 percent of the more than 2 million U.S. soldiers deployed in Iraq or Afghanistan have experienced TBI.

A recent study by psychiatrists from the Iowa City VA Medical Center and University of Iowa Health Care finds that soldiers returning from Iraq and Afghanistan with mild TBI have measurable abnormalities in the white matter of their brains when compared to returning veterans who have not experienced TBI. These abnormalities appear to be related to the severity of the injury and are related to cognitive deficits. The findings were published online in December in the American Journal of Psychiatry.

Human Intelligence Secrets Revealed by Chimp Brains

Despite sharing 98 percent of our DNA with chimpanzees, humans have much bigger brains and are, as a species, much more intelligent. Now a new study sheds light on why: Unlike chimps, humans undergo a massive explosion in white matter growth, or the connections between brain cells, in the first two years of life.

The new results, published in the Proceedings of the Royal Society B, partly explain why humans are so much brainier than our nearest living relatives. But they also reveal why the first two years of life play such a key role in human development.

"What’s really unique about us is that our brains experience rapid establishment of connectivity in the first two years of life," said Chet Sherwood, an evolutionary neuroscientist at George Washington University, who was not involved in the study. "That probably helps to explain why those first few years of human life are so critical to set us on the course to language acquisition, cultural knowledge and all those things that make us human."

Chimpanzees

While past studies have shown that human brains go through a rapid expansion in connectivity, it wasn’t clear that was unique amongst great apes (a group that includes chimps, gorillas, orangutans and humans). To prove it was the signature of humanity’s superior intelligence, researchers would need to prove it was different from that in our closest living relatives.

However, a U.S. moratorium on acquiring new chimpanzees for medical research meant that people like Sherwood, who is trying to understand chimpanzee brain development, had to study decades-old baby chimpanzee brains that were lying around in veterinary pathologists’ labs, Sherwood told LiveScience.

But in Japan, those limitations didn’t go into place till later, allowing the researchers to do live magnetic resonance imaging (MRI) brain scans of three baby chimps as they grew to 6 years of age. They then compared the data with existing brain-imaging scans for six macaques and 28 Japanese children.

The researchers found that chimpanzees and humans both had much more brain development in early life than macaques.

"The increase in total cerebral volume during early infancy and the juvenile stage in chimpanzees and humans was approximately three times greater than that in macaques," the researchers wrote in the journal article.

But human brains expanded much more dramatically than chimpanzee brains during the first few years of life; most of that human-brain expansion was driven by explosive growth in the connections between brain cells, which manifests itself in an expansion in white matter. Chimpanzee brain volumes ballooned about half that of humans’ expansion during that time period.

The findings, while not unexpected, are unique because the researchers followed the same individual chimpanzees over time; past studies have instead pieced together brain development from scans on several apes of different ages, Sherwood said.

The explosion in white matter may also explain why experiences during the first few years of life can greatly affect children’s IQ, social life and long-term response to stress.

"That opens an opportunity for environment and social experience to influence the molding of connectivity," Sherwood said.

Excessive alcohol when you’re young could have lasting impacts on your brain

Alcohol misuse in young people causes significant changes in their brain function and structure. This and other findings were recently reviewed by Dr Daniel Hermens from the University of Sydney’s Brain and Mind Research Institute in the journal Cortex.

"Young people are particularly vulnerable to the damaging effects of alcohol misuse," said Dr Hermens.

Most people have their first alcoholic drink during adolescence and while they drink less frequently than adults, they tend to drink more on each occasion - binge drinking.

The early functional signs of brain damage from alcohol misuse are visual, learning, memory and executive function impairments. These functions are controlled by the hippocampus and frontal structures of the brain, which are not fully mature until around 25 years of age.

Structural signs of alcohol misuse include shrinking of the brain and significant changes to white matter.

In his review, Dr Hermens notes that changes in a young person’s brain caused by alcohol misuse could either represent a predisposition (genetic or environmental) to alcohol misuse, or a marker for future risk of ongoing misuse. Whichever it is, there is no doubt that the more frequent the alcohol misuse, the greater the damage and the less likely the brain is to recover from that damage.

"When the toxicity of alcohol stops your brain from laying down new memories, you experience a blackout," said Dr Hermens. Young people who binge drink may only drink once a week, but on a massive night out they may have three to four blackouts, which begins to cause serious damage to their brain.

One of the best predictors of a person having problems with alcohol is their earliest age of first use. But changing the legal drinking age is not the answer. In Australia the legal drinking age is 18, three years earlier than in the US. Despite the difference in legal drinking age, the age of first use is the same between the two countries.

Another key factor affecting young people who drink is mental health, “poor mental health more than doubles a young person’s risk of alcohol and other substance misuse” says Dr Hermens.

The solution lies in education, treatment and prevention. Dr Hermens and his team have been working with NSW Health to prepare a set of guidelines for health carers to identify and respond to early stages of brain impairment in young people resulting from alcohol misuse. They are currently working on a set of educational charts that inform young people of the risks of irresponsible drinking.

It may be possible to use cognitive remediation to change the drinking habits of young drinkers and prevent relapse. At the same time, vitamin supplements or other medicines may effectively treat some of the structural changes, and it may be possible to develop protective agents that can prevent young brains from the damaging effects of alcohol.

"More work needs to be done in this area. Excessive alcohol use accounts for 4 percent of the global burden of disease. We would save a lot of money and improve the quality of life for millions of people if we could prevent the mental and physical problems associated with alcohol misuse" said Dr Hermens.

Reading, Writing and Playing Games May Help Aging Brains Stay Healthy

Mental activities like reading and writing can preserve structural integrity in the brains of older people, according to a new study presented at the annual meeting of the Radiological Society of North America (RSNA).

While previous research has shown an association between late-life cognitive activity and better mental acuity, the new study from Konstantinos Arfanakis, Ph.D., and colleagues from Rush University Medical Center and Illinois Institute of Technology in Chicago studied what effect late-life cognitive activity might have on the brain’s white matter, which is composed of nerve fibers, or axons, that transmit information throughout the brain.

"Reading the newspaper, writing letters, visiting a library, attending a play or playing games, such as chess or checkers, are all simple activities that can contribute to a healthier brain," Dr. Arfanakis said.

The researchers used a magnetic resonance imaging (MRI) method known as diffusion tensor imaging (DTI) to generate data on diffusion anisotropy, a measure of how water molecules move through the brain. In white matter, diffusion anisotropy exploits the fact that water moves more easily in a direction parallel to the brain’s axons, and less easily perpendicular to the axons, because it is impeded by structures such as axonal membranes and myelin. “This difference in the diffusion rates along different directions increases diffusion anisotropy values,” Dr. Arfanakis said. “Diffusion anisotropy is higher when more diffusion is happening in one direction compared to others.”

The anisotropy values in white matter drop, however, with aging, injury and disease.

"In healthy white matter tissue, water can’t move as much in directions perpendicular to the nerve fibers," Dr. Arfanakis said. "But if, for example, you have lower neuronal density or less myelin, then the water has more freedom to move perpendicular to the fibers, so you would have reduced diffusion anisotropy. Lower diffusion anisotropy values are consistent with aging."

(Image credit: Flickr.com, Courtesy of Luis de Bethencourt)

High blood pressure damages the brain in early middle age

Uncontrolled high blood pressure damages the brain’s structure and function as early as young middle-age, and even the brains of middle-aged people who clinically would not be considered to have hypertension have evidence of silent structural brain damage, a study led by researchers at UC Davis has found.

The investigation found accelerated brain aging among hypertensive and prehypertensive individuals in their 40s, including damage to the structural integrity of the brain’s white matter and the volume of its gray matter, suggesting that vascular brain injury “develops insidiously over the lifetime with discernible effects.”

The study is the first to demonstrate that there is structural damage to the brains of adults in young middle age as a result of high blood pressure, the authors said. Structural damage to the brain’s white matter caused by high blood pressure previously has been associated with cognitive decline in older individuals.

Published online today in the medical journal The Lancet Neurology, the study will appear in print in the December 2012 issue. It emphasizes the need for lifelong attention to vascular risk factors for brain aging, said study senior author Charles DeCarli, professor of neurology and director of the UC Davis Alzheimer’s Disease Center.

First micro-structure atlas of the human brain completed

A European team of scientists have built the first atlas of white-matter microstructure in the human brain. The project’s final results have the potential to change the face of neuroscience and medicine over the coming decade.

The work relied on groundbreaking MRI technology and was funded by the EU’s future and emerging technologies program with a grant of 2.4 million Euros. The participants of the project, called CONNECT, were drawn from leading research centers in countries across Europe including Israel, United Kingdom, Germany, France, Denmark, Switzerland and Italy.

The new atlas combines three-dimensional images from the MRI scans of 100 brains of volunteers. To achieve this, CONNECT developed advanced MRI methods providing unprecedented detail and accuracy.

Professor Daniel Alexander, a CONNECT steering committee member from the UCL Department of Computer Science said: “The UCL team use the latest computer modelling algorithms and hardware to invent new imaging techniques. The techniques we devised were key to realising the new CONNECT brain atlas.”The imaging techniques reveal new information about brain structure that help us understand how low-level cellular architecture relate to high-level thought processes.”