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Showing entries tagged gerontology.  Show all entries

December 3, 2011

Deep Brain Stimulation - A Different Approach


Let's talk about Parkinson's Disease (PD). PD is one of the most prevalent neurodegenerative disorders in the world for people over the age of fifty; as the population has aged and people have started living longer, PD diagnosis has increased significantly. Some of the symptoms include tremor (shaking), akinesia (inability to initiate movement), muscle rigidity, and later in the progression of the disease, slowed speech, blank staring, and dementia. So there are motor and cognitive problems associated with PD, but this post will deal with the reduction of the earlier-onset motor symptoms.

There are two main types of treatment for PD motor symptoms: drugs and deep brain stimulation (DBS). The drugs usually have a compound called L-Dopa, which is a precursor in the formation of the neurotransmitter dopamine, the lack of which has been implicated in inducing the motor symptoms of PD.

The other treatment, DBS, can only be used on some patients, namely those for whom the drugs have had little to no effect and who are also healthy enough to undergo surgery and stay alive for longer than a few years. What they do is create an open-loop (i.e. not a closed circuit) by surgically inserting an electrode into a specific region of the brain, which is connected to a pacemaker-type device called a pulse generator (IPG) that they insert below the neck. Doctors then set the IPG to a certain frequency, so the electrode will send out electrical signals into the brain every so often, and this has been shown to reduce the motor symptoms of PD.

The whole process takes up to a year, with the surgery and adjustments to the properties of the stimulation being continuously modulated until the motor symptoms are reduced and the side effects of the stimulation are not too severe. But, since PD is a progressive disease, the motor symptoms will continue getting worse and the DBS stimulation will continue to need adjustments more and more frequently as the disease progresses.

The issue with this is that no one really knows why DBS works, so all of the adjustments are guesses (systematic guesses, but guesses nonetheless) and patients need to keep coming into the hospital, which costs a lot of money, time, and frustration when their symptoms are not relieved. This is where research in the "closed-loop," or real-time adaptive, DBS comes in. This potential form of DBS also involves a chip that is used to record when natural electrical signaling occurs in the brain region the DBS electrode is in. The recording then sets the properties of the DBS stimulation on the IPG and sets a timer for when the electrode will deliver that stimulation, producing a feedback loop, and decreasing the need for the constant hospital visits.

One study found that given some specific criteria for the wait-time and the number of stimulations, some PD symptoms were reduced (namely akinesia) to a greater extent than with open-loop DBS. However, the study also found many problems with using closed-loop rather than open-loop DBS to alleviate motor symptoms, but these problems have to do with what actually causes the motor problems associated with PD. As such, the study concludes that with more research on the efficacy of closed-loop DBS and on the details of the cause of PD motor symptoms, closed-loop DBS could be used as a potential treatment for PD that will produce not only a more significant reduction of motor problems, but will also enhance the long-term efficacy of using DBS as PD progresses.

Rosin, B., Slovik, M., Mitelman, R., Rivlin-Etzion, M., Haber, S. N., Israel, Z., . . . Bergman, H. (2011). Closed-loop deep brain stimulation is superior in ameliorating Parkinsonism. Neuron, 72(2), 370-384. doi:10.1016/j.neuron.2011.08.023 Retrieved from http://www.cell.com/neuron/abstract/S0896-6273%2811%2900776-8
Posted by      Anna G. at 11:58 AM MST

October 24, 2011

Restoration of Bovine Sanity and a Cure for Neurodegeneration


Mad cow disease. This deadly, presently incurable, brain-eating disease has been the cause of many a steak-lover's trepidation. After all, who wants his brain looking like swiss cheese? It is caused by the consumption or spontaneous generation and accumulation of PrPSc - the misfolded form of cellular prion protein (PrP) - and is responsible for several forms of "swiss cheese brain" besides bovine spongiform encephalopathy (affectionately known as mad cow disease), including the sheep-transmitted scrapie and the human form known as Creutzfeldt-Jakob syndrome, among others. Unfortunately for its victims, PrPSc is much more stable than the properly folded form of the protein and is thus resistant to normal methods of protein digestion (i.e. with protease) and is only known to be degradable via incineration of the infected victim. Clearly, this is an undesirable outcome for the individual who has been unfortunate enough to come into contact with such a protein.

As the misfolded PrPSc aggregates, it forms amyloid fibrils, essentially converting the normally folded PrP to the dark side and eventually causing neuronal cell death and ultimately the death of the organism. However, a recent study of methods to stabilize mouse PrPSc species, published in the Journal of Neuroscience, has shown that prion activity can be reduced by trapping partially digested PrP(27-30) with thienyl pyrimidine compounds.

The process of PrP conversion to the abnormally β-sheet-rich PrPSc form is autocatalytic, that is, it happens spontaneously and independently of other types of molecules. In their study, the researchers discovered that the formation of amyloid fibrils may actually be the "result of a protective process to sequester more dangerous soluble oligomers". As a result, rather than attempting to break the prions apart into smaller, supposedly more easily digested pieces, they decided to attempt to isolate them to avoid increasing the infectivity. Using mouse neuroblastoma cell cultures, they performed various drug assays and blotting techniques, including incubation of fibrils with thienyl pyrimidine compound. When all was said and done, they only observed a minimal decrease in the rate of infectivity, but it was a decrease, nonetheless. They concluded that the binding of thienyl pyrimidine-based drugs diverted dimers and trimers of misfolded protein from their pathological aggregation pathway, trapping them thermodynamically in an energy valley where they could no longer fold into their mortality-causing fibril-forming shape.

Though the study was largely inconclusive, it is clear that meaningful advances were made in discovering that the treatment of prion diseases is not as hopeless as we have believed up to this point. Indeed, the thought of finding a cure seems a daunting task, as the mad cow protein only seems to become more stable under most reaction conditions. However, this study has shown that sometime in the not-so-distant future, the mechanism of misfolding will likely be discovered, a cure for a once incurable disease developed, and we will no longer have to fear prions as much as we have in the past. Also, not only does this research have significant implications for those of us who enjoy a good steak or lamb chop, it may also have far-reaching influence on the treatment of other "prionopathies", including Alzheimer's, Parkinson's and Huntington's Diseases. Since these are diseases which affect a significant fraction of the aging population, research in this vein is critical for the progress of gerontological studies as well.

http://www.jneurosci.org/content/31/42/14882.full
Posted by      Clarinda H. at 12:03 AM MDT

July 31, 2011

What Does a "Senior Moment" Really Imply?


How many of us have been wary of getting into a conversation with a senior citizen because it may take too long and we are in a hurry? When an older person can't remember a name or a specific event, how often does someone think that that person has Alzheimer's or dementia? Why is it that seniors do not get the benefit of the doubt that their brains may be working, just a little bit more slowly? It seems that our society needs to take into account that seniors? brains do experience a certain amount of decline, but that doesn?t mean that the person is losing their mind.

It is a well known fact that as people age they will have trouble remembering to some degree, but how much of that is normal aging and how much is Alzheimer's Disease. It is common to hear about sons and daughters getting frustrated with their older parents when they forget an appointment or a name. The children will have concerns that their parents are getting Alzheimer's. How much of that forgetfulness can be attributed simply to aging? The distinction between normal aging and dementia has always been fuzzy, until just recently.

Dementia, especially Alzheimer's Disease, has been the main focus of gerontological neuroscience for the purposes of diagnosis and treatment. Just recently, a new focus of neuroscience has been to look at what is normal aging for the brain. Through a battery of studies and tests, there seems to be some understanding of what happens to the brain during normal aging.

Long-term memory is one of the most well known types of age related cognitive decline. The left inferior prefrontal region shows less activity in seniors than in young adults during memory tasks. The activity level in this brain region could be increased with cues and "encoding strategies" (Park & Reuter-Lorenz, 2010). Another one of the main deficits that is associated with aging is a decrease in cognitive speed in memory retrieval. This has been shown to be associated with decreased axonal volume or white matter volume (Park & Reuter-Lorenz, 2010). The implications of the research on cognitive speed could be as simple as wait and give them time. There could one day even be a pharmacological treatment that combats the decrease in white matter volume.

There seems to be a simple way to combat some of the decline in the aging brain. Park and Reuter-Lorenz were able to find that "investments made earlier in life, in the form of intellectual, social, and physical enrichment, may increase neural reserve and potential for effective scaffolding as people meet increasing challenges later in life" (2010). With that said, living a rich and thought provoking life in all the above mention areas of life may lead to brain structure that can withstand the negative effects of aging on the brain.

These advances in research could be monumental for every aspect of a senior's life, such as visits to the doctor, daily interactions, and even long term care. Medical care can be simplified by the simple understanding that cognitive deterioration is automatically Alzheimer's Disease or another form of dementia. If a person exhibits normal cognitive aging, a doctor trained in neuroscience would know not to automatically medicate that individual. The doctor would know to educate the senior and his or her family members about ways to better function everyday, like using the cues and encoding strategies. Seniors with normal aging entering long term care would benefit because the care staff would have a better understanding of how to care for them after becoming educated themselves or consulting with the doctor.

The huge advances in gerontology and neuroscience have allowed us as a society to gain a better understanding of what is going on in our grandparents' brains. It has also allowed us to extend the research and the possible benefits to areas outside gerontology to help the entire lifespan.

From the paper by Park, D.C., Reuter-Lorenz, P.A. "Human Neuroscience and the Aging Mind: A New Look at an Old Problem" in Journal of Gerontology.
Posted by      Kelli R. at 8:10 PM MDT




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