Brain Technologies and Alzheimer’s Disease

Written By: Chaahat Gurnani, Palak Purwar, and Shalini Yagnik

Source: https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/

Alzheimer’s is one of the leading causes of death in the world, with more than 5 million Americans living with the disease (Alzheimer’s association). With the increase of Alzheimer’s cases in the world and with no cure yet found, the importance of researching more about the disease and being able to start treatment at early onset is vital for the well-being of patients and their family. Through important technological advancements, doctors will have better tools for Alzheimer’s identification and origin. The more information doctors have about the disease, the greater the chances of developing a cure.

Alzheimer’s disease is a progressive and irreversible disorder in which brain cells and their connections degenerate and die, resulting in the loss of cognitive functionality- some of the main symptoms include memory loss and confusion. The greatest risk for this disease is increasing age, although, early-onset Alzheimer’s can occur in people under the age of 65 in rare circumstances. The disease typically destroys connections in the entorhinal cortex and hippocampus, the areas of the brain responsible for memory. In the process, other parts of the brain are also damaged, such as the cerebral cortex, which plays a key role in thinking, reasoning, language, and behavioral skills. The gradual progression of Alzheimer’s limits a person’s ability to carry out simple tasks and live independently, and is eventually fatal.

To diagnose a possible case of Alzheimer’s, doctors use several tools. Medical professionals conduct neurological exams which may help in identifying the existence of a brain disorder. Then, there are cognition tests to evaluate recall ability, problem-solving skills, and more. Finally, brain imaging through magnetic resonance imaging (MRI) or computerized tomography (CT) scans are used to rule out other diseases that have symptoms similar to Alzheimer’s.

BACKGROUND AND TECH

Brain imaging, or neuroimaging, is crucial to the detection of Alzheimer’s as well as in determining the specific effect of the disease on the brain. To further understand this disorder, enhanced imaging is necessary to look for detailed neural activity, brain tissue, and possible abnormalities. Radioactive tracing, prions, and brain imaging are some of the topics related to the neurotechnologies discussed below. Radioactive tracers give off particles and interact with specific proteins to find problems within the body. Similarly, dye-based compounds “stain” certain cells or tissues, which can also be used to find trace brains and other processes. Prions can be best described as misfolded proteins that can spread their shape to normal variants of the protein. Prion replication results in aggregates, or clumps, that cause tissue damage and cell death. Therefore, the result of this can be fatal and is the cause of many neurodegenerative diseases. There are several brain imaging techniques medical professionals and researchers use to understand the brain, including electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and magnetic resonance imaging (MRI) scans, among many more. An EEG utilizes electrodes to detect and track changes in brain wave patterns; similarly, an fMRI measures brain activity based on blood flow. PET scans use a radioactive drug tracer to show organ/tissue function, which can assist in early detection of Alzheimer's, and an MRI helps give a closer look to structures inside the body. These scans, coupled with symptoms and previous knowledge are the key to diagnosing and potentially treating Alzheimer’s disease.

As a rapidly progressing disease, early detection of Alzheimer’s Disease (AD) is crucial for greater care. With an early diagnosis, a person can start making the best choices for themselves without having to worry about last-minute long-term planning or financial issues, along with being able to take proper care plans, whether that may be participating in possible clinical trials or attempting to slow down the progression of the disease. In order to do so, many different types of technology have been developed to detect the early onset of Alzheimer’s Disease. In general, efficient brain imaging technologies are crucial for determining diseases such as AD.

FUNCTIONAL ULTRASOUND IMAGING

Source: https://www.genengnews.com/insights/functional-ultrasound/

One piece of technology used is Functional Ultrasound Imaging (fUSi) which looks for changes in brain vessels after neural activity. fUSi provides very detailed information about cerebral blood regulations and neurovascular dysfunctions in pathologies, greatly aiding in early Alzheimer’s detection. fUSi has a high spatiotemporal resolution and a large penetration depth, which allows it to better understand the neurovascular interface that is the main pathway to neurodegeneration in AD. fUSi records brain activity over large scales and is used in collaboration with Laser Scanning Microscopy(MPLSM) to provide a detailed view of the neurovascular interface.

IN VIVO MULTIPHOTON MICROSCOPY

Source: https://en.wikipedia.org/wiki/Two-photon_excitation_microscopy

Another type of technology used is in vivo multiphoton microscopy. This is used to determine the relationship between circuit property changes and memory performance. This microcopy selects specific neurons for processing and testing the formation of old memories through the recollection of previous locations, and the formation of new memories through the presentation of new stimuli. The in vivo microscopy tests the changes in plaque size over extended periods of time to determine the progression of Alzheimer’s Disease. In vivo microscopy is also used to identify the anatomy of the human brain, specifically the hippocampus, and observe its degeneration with AD. By then measuring the area, morphometric characteristics, and width of the region on the image, and comparing it with a control healthy brain, using the in Vivo technique, one can determine the amount of degeneration each region has experienced in a given amount of time, keeping track of AD progression.

CONCLUSION

The technological advancements in brain imaging and monitoring neural activity are crucial in determining how Alzheimer's affects the brain and the changes in brain functionality caused by it. Comparing the infected brain images with non-AD brain images will help doctors understand which portions of the brain are responsible for Alzheimer’s affecting millions of people in the United States. Through fUSi, researchers have been able to get detailed information regarding specific path flows while in vivo microscopy has allowed researchers to gather more information on brain anatomy and neural processing using circuit property changes to determine AD progression. Through these scientists have aimed at early onset detection to decrease the intensity of the disease.

Accurate diagnosis, early diagnosis, and preventative care for Alzheimer’s disease is vital to give patients a higher chance of benefiting from treatments and clinical trials that researchers are working hard to develop. Brain imaging is one of the most important resources that medical professionals can utilize, therefore, exploring technologies that enhance their performance is extremely necessary. Some of the more recent developments in this area include a radioactive tracer and dye compounds, which can bind to abnormal proteins and flag the areas to those reading the scans. An example of such protein that affects cognitive ability is PrPSc, an altered form of PrPC. While antibodies have been engineered to prevent this mutation, they may not always be effective or caught in time, which is when tracer tests are more advantageous. Tracer and dye tests have yet to be evaluated in clinical trials, however. Additionally, functional ultrasound imaging will measure changes in neural activity during cognitive tasks. In combination with multiphoton microscopy, which is used to focus on memory performance, the two devices have the potential to detect neuronal activity in relation to Alzheimer’s disease.

Sources

Huesgen, C., Burger, P., Crain, B., & Johnson, G. (1993, January 01). In vitro MR microscopy of the hippocampus in Alzheimer’s disease. Retrieved November 13, 2020, from https://n.neurology.org/content/43/1_Part_1/145.short

Christie, R., Bacskai, B., Zipfel, W., Williams, R., Kajdasz, S., Webb, W., & Hyman, B. (2001, February 01). Growth Arrest of Individual Senile Plaques in a Model of Alzheimer’s Disease Observed by In Vivo Multiphoton Microscopy. Retrieved November 13, 2020, from https://www.jneurosci.org/content/21/3/858.short

C. Luckhaus, M., AS. Fleisher, K., A. Ruitenberg, T., Zlokovic, B., Iadecola, C., A. Montagne, S., . . . A. Kearney-Schwartz, P. (1970, January 01). Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer’s disease. Retrieved November 13, 2020, from https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0799-3

Medical Tests. (n.d.). Retrieved November 13, 2020, from https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests

“Alzheimer’s Disease Fact Sheet.” National Institute on Aging, U.S. Department of Health and Human Services, www.nia.nih.gov/health/alzheimers-disease-fact-sheet.

Deffieux, Thomas, et al. “Functional Ultrasound Neuroimaging: a Review of the Preclinical and Clinical State of the Art.” Current Opinion in Neurobiology, Elsevier Current Trends, 22 Feb. 2018, www.sciencedirect.com/science/article/pii/S0959438817302465.

Larson, Adam M. “Multiphoton Microscopy.” Nature News, Nature Publishing Group, 22 Dec. 2010, www.nature.com/articles/nphoton.an.2010.2.