Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computer model of spread of dementia can predict future disease patterns years before they occur

22.03.2012
Weill Cornell scientists say the program might help patients manage their disease

Researchers at Weill Cornell Medical College have developed a computer program that has tracked the manner in which different forms of dementia spread within a human brain. They say their mathematic model can be used to predict where and approximately when an individual patient's brain will suffer from the spread, neuron to neuron, of "prion-like" toxic proteins -- a process they say underlies all forms of dementia.

Their findings, published in the March 22 issue of Neuron, could help patients and their families confirm a diagnosis of dementia and prepare in advance for future cognitive declines over time. In the future -- in an era where targeted drugs against dementia exist -- the program might also help physicians identify suitable brain targets for therapeutic intervention, says the study's lead researcher, Ashish Raj, Ph.D., an assistant professor of computer science in radiology at Weill Cornell Medical College.

"Think of it as a weather radar system, which shows you a video of weather patterns in your area over the next 48 hours," says Dr. Raj. "Our model, when applied to the baseline magnetic resonance imaging scan of an individual brain, can similarly produce a future map of degeneration in that person over the next few years or decades.

"This could allow neurologists to predict what the patient's neuroanatomic and associated cognitive state will be at any given point in the future. They could tell whether and when the patient will develop speech impediments, memory loss, behavioral peculiarities, and so on," he says. "Knowledge of what the future holds will allow patients to make informed choices regarding their lifestyle and therapeutic interventions.

"At some point we will gain the ability to target and improve the health of specific brain regions and nerve fiber tracts," Dr. Raj says. "At that point, a good prediction of a subject's future anatomic state can help identify promising target regions for this intervention. Early detection will be key to preventing and managing dementia."

Tracking the Flow of Proteins

The computational model, which Dr. Raj developed, is the latest, and one of the most significant, validations of the idea that dementia is caused by proteins that spread through the brain along networks of neurons. It extends findings that were widely reported in February that Alzheimer's disease starts in a particular brain region, but spreads further via misfolded, toxic "tau" proteins. Those studies, by researchers at Columbia University Medical Center and Massachusetts General Hospital, were conducted in mouse models and focused only on Alzheimer's disease.

In this study, Dr. Raj details how he developed the mathematical model of the flow of toxic proteins, and then demonstrates that it correctly predicted the patterns of degeneration that results in a number of different forms of dementia.

He says his model is predicated on the recent understanding that all known forms of dementia are accompanied by, and likely caused by, abnormal or "misfolded" proteins. Proteins have a defined shape, depending on their specific function -- but proteins that become misshapen can produce unwanted toxic effects. One example is tau, which is found in a misfolded state in the brains of both Alzheimer's patients and patients with frontal temporal dementia (FTD). Other proteins, such as TDP43 and ubiquitin, are also found in FTD, and alpha synuclein is found in Parkinson's disease.

These proteins are called "prion-like" because misfolded, or diseased, proteins induce the misfolding of other proteins they touch down a specific neuronal pathway. Prion diseases (such as mad cow disease) that involve transmission of misfolded proteins are thought to be infectious between people. "There is no evidence that Alzheimer's or other dementias are contagious in that way, which is why their transmission is called prion-like."

Simple Explanation for Clinically Observed Patterns of Dementia

Dr. Raj calls his model of trans-neuronal spread of misfolded proteins "very simple." It models the same process by which any gas diffuses in air, except that in the case of dementias the diffusion process occurs along connected neural fiber tracts in the brain.

"This is a common process by which any disease-causing protein can result in a variety of dementias," he says.

The model identifies the neural sub-networks in the brain into which misfolded proteins will collect before moving on to other brain areas that are connected by networks of neurons. In the process the proteins alter normal functioning of all brain areas they visit.

"What is new and really quite remarkable is the network diffusion model itself, which acts on the normal brain connectivity network and manages to reproduce many known aspects of whole brain disease patterns in dementias," Dr. Raj says. "This provides a very simple explanation for why different dementias appear to target specific areas of the brain."

In the study, he was able to match patterns from the diffusion model, which traced protein disbursal in a healthy brain, to the patterns of brain atrophy observed in patients with either Alzheimer's disease or FTD. This degeneration was measured using MRI and other tools that could quantify the amount of brain volume loss experienced in each region of the patient's brain. Co-author Amy Kuceyeski, Ph.D., a postdoctoral fellow who works with Dr. Raj, helped analyze brain volume measurements in the diseased brains.

"Our study demonstrates that such a spreading mechanism leads directly to the observed patterns of atrophy one sees in various dementias," Dr. Raj says. "While the classic patterns of dementia are well known, this is the first model to relate brain network properties to the patterns and explain them in a deterministic and predictive manner."

The study's third contributing author is Michael Weiner, M.D., professor of radiology at the University of California at San Francisco, and the principal investigator of the Alzheimer's Disease Neuroimaging Initiative, funded by the National Institutes of Health.

The study was funded by the National Institutes of Health. None of the authors have any competing financial interest to disclose.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Richard Pietzak | EurekAlert!
Further information:
http://www.cornell.edu

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>