DATE: 3/2/15NAME: JOSIAH KINGTITLE OF ENTRY: ALZHEIMER’STEACHER’S NAME: LINDSEY OWNSCHOOL NAME: EVERGREEN SCHOOLSCHOOL ADDRESS:15201 MERIDIAN AVE N, SHORELINE, WA 98133ENTER THIS POSTER IN THE ENGLISH LANGUAGE LEARNER CATEGORY:NO

ALZHEIMER’S DISEASE:- A BIOMEDICAL RESEARCH PROJECT

This topic matters to me, and others for multiple reasons. Alzheimer’s Disease (AD) is the fourth leading cause of

death for people ages 65 and above in developed countries. In developed countries, the elderly population is rising, and

with it, the number of deaths caused by AD. Many people have lost loved ones to the illness. It currently has no cure

and matters to me specifically because of two reasons. Several of my family members have been lost to this disease and the lack of a cure means that more and more people will continue to die. We can slow parts of the early stages down,

but in the end it does nothing.

Alzheimer’s Disease (AD) is a genetic disorder. AD is a form of neurophysiology. It is also commonly confused with normal aging. Patients with it have multiple thing happening to them:

Brain Tissue is destroyed

There is a depletion of neurons

Depression

Dementia

Synapses of cerebral cortex

Neural Degeneration in:

- temporal lobe

- parietal lobe

- frontal cortex

- cingulate gyrus

- brainstem nuclei (locus coeruleus)

Currently scientists have not been able to stop the disease. Though there are 3 major beliefs surrounding it.

1) AD is the 3rd form of Diabetes. 2) AD is caused by the misfolding of proteins due to plaques and tangles

There are 3 stages of AD:

Early - Short-term Memory Loss (Lasts 2-4 years)

Moderate - Trouble hiding problems (Lasts 2-10 years)

Severe - Confused about time/placing <past or present, location> (Lasts 1-3 years & up)

Cholinesterase Inhibitor:

A cholinesterase inhibitor is drug used to boost levels of a cell-cell communication depleted by AD

-Experiment taken place in 1978

A group of scientists wanted to see the effects of inhibitors and if the cholinergic system pathology has a connection with the cholinesterase

abnormalities in the brain of an AD patient

Acetylcholinesterase and Butyrylcholinesterase activities were bio-medically measured in:

Normal Brain Tissue

An AD brain

A Brain with a Mental Disorder (without AD type abnormalities)

This was to check to see if the results showed were just in AD, or in other mental disorders.

Acetylcholinesterase levels reduced, and Butyrylcholinesterase levels increased in the hippocampus and temporal cortex of an AD brain.

Though, in the other brains observed, no significant changes happened.

There did not seem to be a correlation between the Acetylcholinesterase activity and the subject’s age. But in the hippocampus a positive significant

increase of Butyrylcholinesterase was found in older ages (60-90).

This experiment helped prove the value of cholinesterase inhibitors, following with the advancement of them being officially used with patients.

Namenda:

Namenda is the brand-name drug for Memantine HCI. It is used to treat dementia. The drug acts on the glutamatergic system in the brain. The goal of it is to block NMDA receptors, which bind to brain

cells and block activity of the neurotransmitter glutamate. The point of this is to return the brain to it’s normal way of functioning.

In 2014 a group of scientists did an experiment to determine the usefulness of Memantine HCI (Namenda) in AD subjects.

These patients were split into groups depending on the following:

Patients given just a cholinesterase inhibitor (ChEI)

Patients given ChEI and Namenda

Patients given a Placebo, a pill with no medication at all.

There were 3 trials taken, done at 6 month intervals for 24 months (the 18th month was excused and no data was taken)

At the end of each of the 6 months, all the patients were given behavioral tests.

Patients given the Placebo and those with ChEI and Namenda scored very similarly on these tests. Only mean differences on ADAS and CIBIC were respectively made.

Other tests had no difference. This showed that Namenda has no impact on a patient with AD. Patients with just ChEI scored the highest on the tests given.

This experiment ended up proving that the supposedly miraculous drug to help solve dementia, was actually practically useless.

Anxiety Among AD Patients Test - Medication Needed or Not?<Taken place in 2003>

The goal of this experiment was to see if medication for anxiety should be given to AD patients. This would determine medicines used as well -

cholinesterase inhibitors. Enzymes regulated may affect levels of anxiety, depression, etc.

The experiment was done at the UCLA AD Center. The objective - to compare cross-sectional prevalence (something that that is widespread in

a certain area)/characteristics of anxiety in:

AD

VaD - Vascular Dementia

FTD - Frontotemporal Dementia

A Normal Brain - Control for the experiment

To measure the anxiety levels, the anxiety subscale - Neuropsychiatric Inventory (NPI), scientists gave the NPI to patients.. It is a medical test with

reliability and validity to observe subjects.

The patients were categorized by brain:

They were each given a series of behavioral tests (like the MMSE). These were graded by the NPI and FAQ (Functional Activities Questionnaire).

These tests showed cognitive differences between subjects with different disorders.

They also that patients with AD has less anxiety than the other people.

“AD anxiety levels were inversely related to MMSE scores” - they were worse with more severe dementia -- Jama Neurology.

This showed that patients with a younger onset age for AD (65 and below) were more prevalent. These were correlated with disabilities measured by

FAQ. The data from this ended up displaying that anxiety is common among patients with different forms of dementia. It seems that anxiety in

AD is most common in subjects with:

more severe cognitive deterioration

earlier onset age

This changed the way cholinesterase inhibitors for anxiety were given out to people with AD, because stress is bad for everyone in general, and this

can be regulated.

Dr. Ong is a gerontologist (a doctor who cares for the

elderly) at the University of Washington. He treats the

old, many of whom have been diagnosed with AD. He

has not seen much changes in the treatment of his

patients, but has knowledge and opinions on them.

Breakthroughs in his career would be that of being

able to make earlier diagnostics of AD patients using

“a combination of clinical examination, blood tests,

and brain scans.”

These experiments will help me in a few ways. Firstly, if a family member, friend, or I ever get Alzheimer’s, I will already be in the knowing of how it can be treated. They also help me realize the importance of AD, and biomedical research. The fact of knowing these raises my own awareness. As losing family to the disease I myself have a higher chance of getting it. This is important information. It affects life-changing decisions I make. Knowing this now, rather than later gets me closer to finding a cure. The sooner i find one, the more opportunity I’ll have to change the lives of my own family, and others suffering from AD as well. Never close the door on an opportunity, until you’ve had a chance to hear the offer.

I think that everyone understanding the importance of scientific research is a key role in life. Being able to know about all the ways different things happen is not only right, but a moral freedom. As a society we depend on each other. If one person can’t help, evolution doesn't go as smoothly. I also believe that with the ability of everyone knowing, more lives will saved. Less people will suffer. If everyone has the knowledge and ability to know, then we would be better as a whole. We could cure more diseases, and help those in need. Pain would also come along less. Families wouldn't be separated. The world itself would be a better place. And i know that if this were to be true, family of my own may would have had a chance. Biomedical research is needed for the advancement and well being of the human race. The experiments have also given me the ability to spread the word, to raise more awareness. They could help families not lose loved ones, like i did. “Knowledge is freedom and with freedom comes understanding” - Julie Garwood. This is how differences are made. And from those differences, a new and prosperous civilization. One from which the foundation of a life of healthy being. Being born from the importance of knowing, and understanding - of research.

Schneider, Lon. S., Philip S. Insel, Michael W. Weiner. Treatment With Cholinesterase Inhibitors and Memantine of Patients in the Alzheimer's Disease Neuroimaging Initiative. Vol. 68. 2011. Abstract <http://archneur.jamanetwork.com/article.aspx?articleid=802034>

S.K., Sonkusare, Kaul, C.L., Ramaro, P. Dementia of Alzheimer’s disease and other neurodegenerative disorders—memantine, a new hope. Vol. 51. 2004. Abstract <http://www.sciencedirect.com/science/article/pii/S1043661804001379>

Namenda. N/A. Namenda. 2015. Web. 23 Feb. 2015. <www.namenda.com>

- ABSTRACT. Perry, Elaine P., R.H., et al.CHANGES IN BRAIN CHOLINESTERASES IN SENILE DEMENTIA OF ALZHEIMER TYPE. Vol. 4. 2008. Abstract. <www.onlinelibrary.wiley.com/doi/10.1111/j.1365-2990.1978.tb00545.x/abstract>

What Is Alzheimer's?. N/A. Alzheimer's Association. 2015. Web. 23 Feb. 2015. <www.alz.org/alzheimers_disease_what_is_alzheimers.asp>

Monte, Suzzane, Jack. R. Wands. Alzheimer's Disease Is Type 3 Diabetes-Evidence Reviewed. N/A. 2008. Abstract. <www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/>

Porter, Verna, William Buxton, et al. Frequency and Characteristics of Anxiety Among Patients With Alzheimer's Disease and Related Dementias. Vol. 15. 2003. Abstract. <http://neuro.psychiatryonline.org/doi/10.1176/jnp.15.2.180>

Ong, Thuan. Personal Interview. 23 Feb. 2015

For Alzheimer’s disease an acetylcholinesterase inhibitor (a drug that stops enzymes from breaking down neurotransmitters) is commonly used. These can be subtle - the inhibitors, and medication depends on when the subject begins to take them. Researchers are currently looking into the optimal time to begin taking such medications. When asked about his views of the brand name drug -Namenda (Memantine HCI), Dr. Ong said-- “Although marketed as another possible medication to treat Alzheimer’s dementia, the clinical usefulness of this medication is debatable. It hasn’t really moved or changed the way we care for patients with Alzheimer’s disease.”

115 Patients Probable AD

43 Patients VaD

33 Patients FTD

40 Patients Control subjects – elderly

431 Patients With Mild AD MMSE scores of 20-30

697 Patients With Moderate to Severe AD

MMSE scores of 10-19

What IS AD? Intro:The Interview:

Namenda:

ChEI (1):

ChEI (2):

Bibliography

Conclusion:

Reflection On Biomedical Research :