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Detecting Neurodegenerative Diseases Before Damage Is Done

The brain has amazing capacity to overcome large deficits, which means that by the time a neurodegenerative disease becomes apparent, the damage is extensive. In the case of Parkinson's disease, for example, more than half of the midbrain region called the substantia nigra can be completely destroyed without any evidence of a problem. But once a threshold of 65- to 70-percent damage has been crossed, the trajectory goes over a cliff and the telltale motor symptoms of Parkinson's appear.

Alzheimer's disease is similar. Plaques and tangles can be developing in the brain and neurons can be dying, but the compensatory mechanisms of the brain are so great that there are no behavioral symptoms—until the brain can no longer overcome the damage. By that time, there may be no hope for treatment. Unfortunately, we are a long way away from having any sort of treatment that can repair the massive destruction that has occurred by the time the disease is detected.

In SRI's Center for Neuroscience, my colleagues and I are searching for an indicator that could help diagnose neurodegenerative diseases much earlier, hopefully years before the damage is so extensive that nothing can be done. If a marker is found in both humans and animal models, it could also help guide the development of new treatments and be used to monitor patients to determine if potential treatments are effective.

Our search for a translational biomarker for measuring the presence and progression of neurodegenerative disease centers on the use of the electroencephalogram (EEG).  Put simply, an EEG is a measure of the sum of all electrical activity across different regions of the cerebral cortex. Healthy neurons produce electric currents in the process of releasing neurotransmitters and relaying signals. When neurons get sick, their electrical patterns can change long before they die. When large numbers of cells start changing their electrophysiological properties due to the progression of a neurodegenerative disease, we believed there would be measurable changes in the readout of the EEG. And that is what we found in Huntington's disease, as described below.

Using EEG to diagnose brain dysfunction is not a new idea.  Numerous studies have found changes in the EEGs of patients suffering from various neurodegenerative diseases as well as in animal models of neurodegenerative diseases. However, finding EEG changes that are indicative of the presence of disease prior to the onset of symptoms has been difficult to ascertain.

Huntington's disease is unique among the neurodegenerative diseases in that it is the only major one for which we know the major cause with certainty. In Huntington's disease patients, a genetic mutation in the Huntingtin gene produces a change in a protein that makes it toxic to neurons. Because Huntington's disease has a known inheritable cause, we are able to determine if a person has the disease decades before they become symptomatic. Thus, we recognized the opportunity to study the diagnostic value of EEG in Huntington's disease patients at various stages of the development of the disease. 

UCLA Professor Andrew Leuchter has studied EEG patterns in Huntington's disease patients and several years ago published an important finding about how EEG patterns changed in pre-symptomatic Huntington's disease patients compared to controls. These changes progressed as patients got closer to being symptomatic. Dr. Leuchter was able to use EEG as a biomarker that could identify a patient having the disease 10 years prior to its onset. This work validated the concept that the EEG can be used as a biomarker for the presence and progression of a neurodegenerative disease.

For the last three years, SRI researchers have been studying EEG patterns in mice that have a condition similar to human Huntington's disease. Our findings that an EEG “signature” could indeed identify early changes in the brain were recently published in the journal Brain. SRI's findings and Dr. Leuchter's findings both support the hypothesis that the EEG can be used to diagnose neurodegenerative disease and that it might also be used as a biomarker to help measure the efficacy of potential new therapeutics.

12 Comments

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Neeraj Rawat

The idea is very interesting and perfectly logical we just need optimize our ECG analysis part...

Anonymous

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Lina

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Mahtani

Could the eminent neurosurgeons find a cure for ALS i.e amyotrophic lateral sclerocis . I am very anxious to know details of treatment if any.

Ervin Ormon

After reading about the research being done by SRI with the EEG to try and determine if there are translational bio-markers for measuring the presence and progression of neurodegenerative disease, it occurred to me that it would be a could idea to study the adult children of older people that have already been diagnosed with any neurodegenerative diseases. For example lets say we have a man or a women in there fifties that has a parent that has been diagnosed with a neurodegenerative disease, then the healthy brains of the offspring in there fifties and sixties could be studies over a period of 5 to 15 or more years to see which if any of them develop neurodegenereative diseases. I believe that it is more likely that the children with parents having developed similar diseases will be more likely to develop them also due to genetic similarities, diet, environment and a host of other factors they may have in common. I also have some ideas on developing computer software to help analysis the data to find any correlating patterns. Many questing have to be asked of the individuals to extrapolate the information. I am a software developer and I found the article to be thought provoking.

Magno

Wow! Great to find a post knocking my socks off!

J P Singh

I think that the research of EEG patterns will go a long way helping patients who have both neuro and kidney failure diseases , my mother had symptoms of the neuro disease due to my mothers acute kidney and diabetic problems. Today the death of neurons in our brain and the disfunctioning of the various parts of our body are due to stress improper health diet and pollution issues as well . So we have to go a longway before we can find a solution to this though EEG and research will help a lot.There is a definate link between diabetes, kidney failure and the degenerative process of the neurons in the brain and a lot more research has to be done to prevent more loss of human lives .

Michelle Agnew

yes yes... interesting... I have a dear friend who has basically multiple organ failure... but the kidneys are the worst as they produce high ammonia levels and his liver is sick and failing and cannot rid of the ammonia quick enough hence....dementia type behavior. He tried getting out of his friends car on the 10 fwy @ 70 mph; he didn't even recall doing this! The medication basically is hiigh doses of lasix (so you are urinating non stop) and this other stuff "lactalose" sp? that makes you have to be in the bathroom non stop as well. Not a very pleasant way to live. So I hope they do MORE and MORE research... it is critical to support your local teaching hospitals , etc. Thanks... Michelle

alangilan marquez go

this article is both timely and highly informative. I wish there could be an extensive discussion about a condition called bipolar. Is it also a neurodegenerative disease? can it be an adverse effect of long term substance abuse? If so, how effective are the present drugs for it? Thank you very much for whatever you can share on this.

Madelyn

I am desperate to know why my speech has become so wretched, AND why I cannot think clearly. If I am saying a fairly long sentence[s] I often can't remember how it is to end. Then cannot quote my first utterance. I am 63 - this started 3 yrs ago.

I think.

Help?

Anonymous

What about PET scans, and what about really good psycho-social questionnaire/ assessments or timed tests?
If everyone was given a baseline assessment in their 20's per their doctors office, then when needed decades later another testing event could compare results. What's so hard about that? We can test memory- short and long term that way. We should be able to test processing abilities and processing speed that way and the sophistication of a writing sample.
At least that is something to put into place that shouldn't cost too much money for the masses.

Phil Barbour

The redundancy of the brain is amazing. I believe a study at the Cleveland Clinic maping electronic stimulation of stroke patients currently ongoing. My guess is that a chemical trail is left in the brain which should be searched out. The basic chemical research of the brain is on going and each clue will lead on to new advances.