Running head: LIT REVIEW

Alzheimers and Its Progress: A Review of the Literature Juan Delgado University of Texas at El Paso

LIT REVIEW

Abstract Alzheimers disease, a form of dementia, has been affecting people for hundreds of years. This disease is generally known for causing memory loss to the elderly. As a result, organizations have begun to take action and provide researchers with funding in hopes of implementing methods to reduce the impact of such a hazardous disease. This literature review provides general information about the disease as well as its possible causes. It reflects on those people affected in the United States and provides some insight on how their lives have changed when dealing with the disease. Along with personal interviews, this paper also provides information on whether research for Alzheimers has progressed and what else needs to be done in order to do so more effectively. It also provides information about research on increased funding effects and what needs to be done in order to obtain funding for research.

LIT REVIEW

Alzheimers and Its Progress: A Review of the Literature As time has elapsed the worlds population has grown exponentially. This increase in population has naturally led to the increase and development of new diseases. Many of those new diseases have been controlled by the rapid increase in medical research. In an effort to put an end to the destructive paths of those diseases, some form of preventions has been created. There are many diseases with vaccines or pills that control and in some cases cure the person from such disastrous effects. Despite the new knowledge of scientists, there are many common threats, such as Alzheimers, that have yet to be controlled. In order to better understand the disease and the possible options to developing a cure, the following four questions will be examined thoroughly: 1. How is Alzheimers disease defined? 2. How many people does Alzheimers affect in the United States?

LIT REVIEW

3. Has any progress been made towards finding a cure for this disease? 4. Would an increase in funding help to achieve a cure for Alzheimers? This literature review will focus on these four questions and provide information about the disease, its causes and prevention.

How is Alzheimers disease defined? Alzheimers is a very grave disease that has been present for thousands of years. With the advancements in technology and medical research, it is surprising to discover that the population affected with the disease is increasing in numbers. Instead of lowering the amount of people affected, each day more and more people find themselves dealing with Alzheimers. The exact cause of Alzheimers disease remains a mystery; even after a main factor causing the disease was discovered. Alzheimers disease is a progressive, degenerative disorder that attacks the brains nerve cells, or neurons, resulting in loss of me memory, thinking and language skills, and behavioral changes. (Alzheimers Foundation of America, 2013). Alzheimers is the most common form of Dementia. Dementia describes a set of symptoms that include loss of memory, mood changes, and problems with communication and reasoning. Dementia is a progressive disease, meaning that the symptoms will gradually get worse (Alzheimers

LIT REVIEW Society, 2013).

The exact causes of Alzheimers are unknown; however there are many assumptions on what causes the disease. This form of dementia correlates directly with old age (Alzheimers: An Urgent Epidemic, 2008). The most common age to contract Alzheimers is sixty. The risk of obtaining the disease increases every year. One percent of sixty five year olds have Alzheimers, ten percent of seventy five year olds have it as well, and about twenty percent of eighty five year olds deal with the disease currently (Alzheimers: An Urgent Epidemic, 2008). These are alarming numbers, but nevertheless prove that old age is a direct correlation with this type of dementia. Another assumption is the deprivation of sleep. Studies performed on mice indicate that continuous sleep deprivation for five days produces loss of memory and may be a cause of Alzheimers disease (Rahman et al., 2012). According to this study, sleep disturbances and dementia increase with advanced age and about forty five percent of Alzheimer patients have disruptions in their sleep. Clinical evidence showed that people who suffer from chronic insomnia are about eleven times more likely to develop Alzheimers in latter life. (Rahman et al., 2012). This study by Rahman and company demonstrated that sleep plays an important role in memory formation and sleep deprivation is one of the major causes of Alzheimers. This also correlates directly with old age since it is rare people of a mature

LIT REVIEW

age obtain regular sleep. How many people does Alzheimers affect in the United States? Alzheimers disease affects twenty four million people worldwide. This number is expected to double to forty eight million in twenty years, and then double once more. (Alzheimers: An Urgent Epidemic, 2008). The areas in which Alzheimers is present in larger numbers are those countries with a poor economy. However it also affects thousands of people in the United States. In the United States alone over 500, 000 people are affected. The most alarming part is that there are around 50,000 new cases of this disease each year (Alzheimers: An Urgent Epidemic, 2008). Alzheimers research is expensive, hence another reason to why there is no cure yet. Research takes time, and in this case money which isnt available in every part of the world. In the United States, the majority of people affected are those over the age of sixty (Alzheimers: An Urgent Epidemic, 2008). This as mentioned previously is associated with sleep deprivation, and the fact that dementia develops in the latter years of a persons life. Researchers also found out that Alzheimers is most commonly seen in women. (Alzheimers Foundation of America, 2013.) Men with Alzheimers disease tend to develop more aggression-physical, verbal, and sexual- than women do as the disease progresses (Thompson Jr., 2013). Women with Alzheimers tend to become more reclusive and

LIT REVIEW

emotionally unstable. They hoard items more often than men do, and refuse help. (Thompson Jr., 2013). On Average, a girl born is expected to live to age 80, while a man is expected to live around 75 years. This is one of the major differences in determining why women tend to be affected more by the disease than men. Women tend to live longer, and hence be more vulnerable to the greatest risk factor associated with Alzheimers, old age.

Has any progress been made towards finding a cure for this disease? There has been progress towards finding a cure and there will continue to be as long as advancements in medicine keep occurring. Researchers have discovered many things such as proteins affecting the disease, the correlation with old age, and also sleep deprivation. The idea behind discovering the cure is detection. People begin treatment for the disease once they start developing memory loss. Once people forget where they parked constantly, or how to get to a friend or relatives house, the disease is treated. However the disease actually begins 10 to 15 years prior to the stage at which symptoms begin to appear. By this time, patients have already lost 40% to 50% of their brain cells, which, essentially, is at the end stage of the disease (Black, 2012). The best way to treat this disease is by detecting it early. Diabetes can be treated well if

LIT REVIEW

detected in the early stages, however if detected after the person has had the disease for ten or twenty years, then that patient already would have kidney failure. The same concept is trying to be applied to Alzheimers. If the disease is detected early there can be some sort of intervention and perhaps even a greater understanding. Researchers such as Black are now attempting to discover the disease in its early stages, which will allow them to learn more about the disease and ultimately find a cure. There are some professors at The University of Texas at El Paso (UTEP) performing research on Alzheimers disease. These professors are Mahesh Narayan, Ph.D., associate professor of chemistry at UTEP, Manuel Miranda-Arango, Ph.D., assistant professor of biological sciences, and Edward Castaneda, Ph.D., chair and professor of psychology (UTEP news, 2013). According to this press release, Dr Narayan stated, In epidemiology studies in the Indian subcontinent, it was noticed that the people there presented one sixth the rate of Alzheimers disease of those in the U.S., he said. This seems to suggest that there is something in the diet that might prevent the disease. Dr. Narayan has been performing research on Alzheimers by studying proteins and the way they fold. The professors ultimate goal is to collaborate with food manufacturers and have curcumin, or other neuroprotectants, laced in potato chips or milk to innocuously inoculate the public form from the sporadic onset of the neurodegenerative disease (UTEP news, 2013). In an interview performed April 6, 2013, Dr.

LIT REVIEW

Narayan stated, We are attempting to find the cure that we believe might have to do with peoples diet. We are studying curcumin, which can stop proteins from folding basically and has an effect on Parkinsonss disease. So we will see how that affects Alzheimers as well. (Dr. Mahesh Narayan, personal communication, April 7, 2013).

Would an increase in funding help to achieve a cure for Alzheimers? The disease has been studied intensely since the 1980s. Although it is still a work in progress, there is hope if the adequate research funding is provided. Since late 1980s the use of physical and chemical restraints has been significantly reduced. (Albisu, 1999). The special needs of individuals with dementia are acknowledged more each day. Increased funding would help train staff and obtain more resources. Anytime there is a disease with no cure, it is essential to provide funding. However when there is no cure, research for the disease will naturally be extremely expensive. Organizations such as Alzheimers Society and Alzheimers Foundation of America are another valuable source of funding for research towards dementia. They do this by fundraising money in volunteer events. A perfect example of this is the Walk to End Alzheimers, which occurred in El Paso in September. In events like these, many volunteers donate their money and time and walk around

LIT REVIEW

10

a specific area. Another form of obtaining money is the telethon. This is a national event in which anybody can donate money. All of this money goes directly towards research in hopes that scientists can keep finding innovative treatments for patients, and ultimately develop a cure. When asked about how complicated it is to obtain funding for research, Dr. M. Narayan stated. Yea, oh yeah, it is very difficult. We have to write a paper, which is in a sense a grant form. But it better be good and you better explain well what you plan to do with the money and how you will use it otherwise the funding goes elsewhere. If it were easy everyone would get funding. (Dr. Mahesh Narayan, personal communication, April 7, 2013). Image 1. The image below contains the table of contents of an example NIH grant. This is a grant written to obtain funding for a research project.

LIT REVIEW

11

Program Director/Principal Investigator (Last, First, Middle):

Kirken, Robert A. 2G12RR008124// Maldonado, Rosa, A

The name of the program director/principal investigator must be provided at the top of each printed page and each continuation page.

RESEARCH GRANT TABLE OF CONTENTS

Page Numbers

Cover Page.................................................................................................................... ............................ Face Page..................................................................................................................... ............................. Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells ................................................................................................ ......... Table of Contents ............................................................................................................. ........................ Detailed Budget for Initial Budget Period ..................................................................................... ......... Budget for Entire Proposed Period of Support............................................................................................. Biographical Sketch Project Leader (Not to exceed four pages) ......................................................... Other Biographical Sketches (Not to exceed four pages each See instructions)............................... Resources ..................................................................................................................... ............................ Checklist............................................................................................................................... ..................... Research Plan ................................................................................................................. ..........................
1. 2. 3. Introduction to Revision Application .................................................................................................................... Specific Aims * ................................................................................................................................................... Research Strategy * ........................................................................................................................................... 3a. Background and Significance ....................................................................................................................... 3b. Preliminary Studies ...................................................................................................................................... 3c. Research Design and Methods .................................................................................................................... 3c.1. Timetable and milestones for product development .......................................................................... 4. 5. 6. 7. 8. 9. Inclusion Enrollment Report (Renewal or Revision applications only) ................................................................. Bibliography and References Cited/Progress Report Publication List ................................................................. Protection of Human Subjects ............................................................................................................................. Inclusion of Women and Minorities ...................................................................................................................... Targeted/Planned Enrollment Table .................................................................................................................... Inclusion of Children ............................................................................................................................................

1 2 3 5 6 7 9 12 20 21 22
22 23 23 23 24 27 28 28 29 29 29 29 30 31 31 32 32 35 35 35 35

10. Vertebrate Animals .............................................................................................................................................. 11. Select Agent Research ........................................................................................................................................ 12. Multiple PD/PI Leadership Plan ........................................................................................................................... 13. Consortium/Contractual Arrangements ............................................................................................................... 14. Letters of Support (e.g., Consultants) .................................................................................................................. 15. Resource Sharing Plan (s) .................................................................................................................................. 16. BSL3/4 Access .................................................................................................................................................... 17. Potential Core Needs .......................................................................................................................................... 18. Which Theme the Application Fits .......................................................................................................................

Consortium/Collaboration Documentation (if applicable): Face Page, Detailed Budget for Initial Budget Period, Budget for Entire Proposed Period of Support, Checklist........................................ Other Support (for all personnel listed on budgets) ........................................................................... . NO APPENDICES ARE ALLOWED ON RCE APPLICATIONS

37

* Items 2-3 not to exceed 5 pages.

PHS 398 (Rev. 6/09) Page 5 Form Page 3

This specific paper includes 40 pages, however this number varies depending on what the proposed plan is. Although this particular grant example is not related to Alzheimers, every grant must have specific aims, background/significance, research design and methods, preliminary studies, bibliography, letters of support, agent research and potential core needs amongst other requirements. This is the difficulty professor Narayan was referring to during the interview Whether an increase in funding would help find a cure is uncertain,

LIT REVIEW

12

however funding is essential in order to perform any type of research. Conclusion Alzheimers disease has challenged and killed humans for thousands of years. However, various assumptions have been made towards possible causes. The discovery of cases such as sleep deprivation and old age have increased the research goals dramatically. Although there is no cure, the funding being provided and the many people involved are making a difference in the race to find a cure. As medical research continues to evolve, organizations such as Alzheimers Society and Alzheimers Foundation of America, continue to provide hope, information about the disease, and help available to those affected.

LIT REVIEW

13

References Alzheimer's Foundation of America. (2013). Caring for the nation one person at a time. Retrieved from http://www.alzfdn.org/? gclid=CLvpmo_q5LUCFdSnPAodB0AAJw Actionalz. (2008). Alzheimer's: An urgent epidemic. Retrieved from http://www.youtube.com/watch?v=ZOZBWqd5JAQ Alzheimer's society. (2013). Retrieved from http://www.alzheimers.org.uk Black, K. (2012, September). On the Cusp of a Cure. Usa today magazine, 141(2808), 66-67. Albisu, K. (1999). Alzheimer's Association. Nursing homes: Long term care management, 48(12), 98. Rahman, H., Muralidharan, P., Silvaraman, D. & Saha, D. (2012). Continuous Sleep Deprivation for 5 days produces loss of memory in mice and may be a cause of Alzheimer's. Annals of biological research , 1(4), 185-193. Wierenga, C. E. & Bondi, M. (2011). Dementia and Alzheimer's Disease: What We Know Now, Generations, 35(2), 37-45. Thompson Jr., D. (2013). Alzheimer's: A woman's disease?. Retrieved from http://www.everydayhealth.com/alzheimers/alzheimers-and-gender.aspx UTEP NEWS. (2013). Utep professor studies kitchen cure for Alzheimers and Parkinsons disease . Retrieved from http://newsuc.utep.edu/index.php/latestnews-2/870-utep-professor-studies-kitchen-cures-for-alzheimers-and-parkinsonsdisease