Questions answered in this video include:

1. What is Alzheimer’s Disease?
2. Is Alzheimer’s Disease the same as Dementia?
3. How common is Alzheimer’s Disease in Canada?
4. What changes are seen in the brains of patients with Alzheimer’s Disease?
5. Is there a genetic component to Alzheimer’s Disease?
6. What are the risk factors for developing Alzheimer’s Disease?
7. What are some of the treatment options available to individuals with Alzheimer’s Disease?
8. What other possible treatment options are currently being explored by researchers?

Notes on Dr. David Westaway:

Dr. David Westaway is an internationally acclaimed researcher and director of the Alberta Centre for Prions and Protein Folding Diseases at the University of Alberta. Here,  he has become one of two inaugural Prion Institute Scholars. The scholar program was recently established by the Alberta Prion Research Institute, which funds research into the prevention and management of prion-related diseases, like Alzheimer’s and Parkinson’s disease.

Previously a researcher with the Centre for Research in Neurogenerative Disease at the University of Toronto, Westaway is a molecular biologist who completed his postdoctoral training at the University of California with Nobel laureates Harold Varmus and Stanley Prusiner, where he helped to define the molecular biology of prion diseases. His work on cellular prion protein and two related proteins has led to insights about Alzheimer’s disease.

Most neurodegenerative diseases like Alzheimer’s disease are protein-folding diseases. These diseases are caused by prions, a type of protein which causes neurodegenerative diseases when they fold incorrectly. This field of study is relevant to the public on many levels. Prion research is an “enormously practical problem on a very day-to-day level with an impact on agriculture,” says Westaway. Prion diseases are also critical to human health and “some of the tools of prion research have been put to good effect in neurodegenerative diseases that are common in humans.”

-adapted from an article on the website of “Canadians for Health Research

Alzheimer’s Disease:

Dementia can be defined as a serious loss in cognitive ability attributed to factors beyond natural aging. Alzheimer’s disease is the most common form of dementia; affecting an individual’s memory, cognition and behaviour. Currently the incidence rate of Alzheimer’s disease in Canada is approximately 1 in 11 individuals over the age of 65, making Alzheimer’s disease a common disease amongst senior citizens. While Alzheimer’s disease is currently an incurable disease, and treatment options mainly focus on the management of the disease, a significant amount of research is being performed in order to learn more about this complex disease and hopefully develop more advanced treatment techniques.

Pathophysiology

The pathophysiology of a disease is basically describing the abnormal changes occurring in the body that causes the symptoms experienced in patients with that particular disease. As such, the pathophysiology of Alzheimer’s disease will describe what is happening in a patient’s brain as the disease progresses (however it may not describe what causes these changes to occur). Alzheimer’s disease is characterized by the loss of neurons (brain cells) and the connections between neurons (known as synapses). This results in the deterioration of various parts of the brain, including the parietal and temporal lobe, as well as parts of the frontal cortex. The deterioration of these areas of the brain leads to the symptoms experienced by patients with Alzheimer’s disease (including memory loss, loss of cognition, etc.). The exact cause of this deterioration is not well understood however, an increased number of substances called amyloid plaques and neurofibillary tangles are noted in the brains of patients who have Alzheimer’s disease.  Amyloid plaques are insoluble protein structures that form around the brain cells, while neurofibrillary tangles are incorrectly developed proteins (Tau proteins) that accumulate inside the brain cell. As you may notice, both amyloid plaques and neurofibillary tangles are forms (or mis-forms) of proteins. As such, Alzheimer’s disease has been identified as a protein mis-folding disease caused by the accumulation these abnormally formed proteins.

The cause of the proteins accumulating in and around the brain cells of Alzheimer’s patients is not yet fully understood, however mutations in several genes have been identified as events leading to the protein accumulations. As genes serve as the ‘instructions’ for the construction of proteins in the body, genetic mutations could give rise to the formation of proteins that can interfere with the normal functioning of the body. With regards to Alzheimer’s disease, mutations of the APOE gene has been found cause the symptoms associated with Alzheimer’s disease, with individuals carrying this genetic mutation having an increased chance of being diagnosed with Alzheimer’s disease. The other possible genetic links are not as clear, but current research is looking into further identifying the mutations and genes that can lead to the protein mis-folding seen in patients with Alzheimer’s disease.

Causes and Symptoms

The exact cause of the disease is not fully understood, but there are several theories that attempt to explain certain aspects of the disease. One theory is that Alzheimer’s disease is caused by a deficiency in the neurotransmitter acetylcholine. A neurotransmitter is a molecule that neurons (brain cells) use to communicate with other cells in the body. According to this postulate (“theory”), the deficiency in acetylcholine is the primary cause of the cognitive impairment seen in patients with Alzheimer’s disease. Many current drug treatments are based on this theory however several other researchers have proposed different postulates to explain the cause of Alzheimer’s disease. One of these alternative causes focuses on how genes play a role in Alzheimer’s disease. The influence of the APP gene and APOE4 gene are thought to cause excess amyloid plaque build-up and account for the neuron death and cognitive impairment seen in patients with Alzheimer’s disease. Finally, the “tau hypothesis” proposes that abnormalities with the tau proteins present in the human body that result in the tau molecules clumping together and forming neruofibrillary tangles, strongly correlates with the cell death seen with Alzheimer’s disease.

Whatever the cause, it has been found that the damage to the brain starts about 10 years before the initial onset of symptoms. During this time, the connections between neurons in the brain become weak and ineffective at transmitting impulses that are needed for the full function of the brain. As the connections are slowly lost and the neurons die, parts of the brain become weaker and symptoms can begin to appear. For instance, when the neurons begin to weaken and die in an area of the brain called the Hippocampus, memory loss starts becoming apparent. In fact, severe memory loss is often an early symptom of Alzheimer’s disease, however it should be noted that memory loss can be a symptom associated with a variety of other disease as well. Other early symptoms of Alzheimer’s disease include a decline in cognitive ability, including difficulty in tasks requiring visual/spatial skills as well as impaired reasoning and judgement.

As the disease progresses, a number of routine daily activities will become increasingly difficult, such as speaking (due to a decrease in vocabulary) and tasks requiring motor skills (ie: tying a shoe, getting dressed). In addition, the neurological effects will become increasingly more profound, leading to possible delusions, personality and emotional changes, and losing the awareness of one’s condition and environment.

In the final stages of the disease, the patient will be fully dependant on a caregiver and may lose their ability to communicate verbally (however they can still hear and interpret messages), eventually lose the ability to independently eat and drink (due to decreased muscle mass) and become more fatigued and tired. While Alzheimer’s disease is a terminal disease, the more common cause of death for Alzheimer’s patients is due to external factors, such as infections or pneumonia.

Treatment

As previously mentioned, current treatment options focus mainly on the management of symptoms rather than the treatment of the disease. The two main types of medications used to manage the symptoms of Alzheimer’s disease are Acetylcholinesterase inhibitors and memantine.  Acetylcholinesterase inhibitors are often used to manage mild to moderate Alzheimer’s disease by blocking the acetylcholine neurotransmitter. The most common side effects of this treatment are nausea and vomiting. Memantine is a NMDA receptor antagonist and works by blocking the action of the NMDA receptors (which respond to the neurotransmitter glutamate). This treatment has shown to be effective in treating moderate to severe Alzheimer’s disease. Side effects of memantine include hallucinations, confusion, dizziness, headaches and fatigue.

Other non-medicinal treatment options may be effective at managing Alzheimer’s disease including the use of emotional intervention methods. Methods of emotional intervention include using reminiscence therapy and sensory integration. Reminiscence therapy is performed by having the patient recall different memories from their past sometimes utilizing memory aids such as pictures. This therapy may be used to help with cognition and mood. Sensory integration is performed by altering the patient’s surrounding by including differ objects that are both soothing and stimulating to one’s senses (such as lava lamps). This type of room is often called a snoezelen room and is also used as a sensory therapy for other mental disorders. While little scientific research has been performed to determine the effectiveness of these therapies, there may be some evidence that these therapies can help with the patient’s mood and emotions.

It is also essential that a patient with Alzheimer’s disease has adequate care from a caregiver, as during the final stages of Alzheimer’s disease, many normal functions (such as eating) will be hard to perform without assistance. In addition, the caregiver is able to provide emotional support for the patient, further necessitating a caregiver for the individual.

Some researchers are also looking into how certain lifestyle changes/activities could prevent or delay the onset of dementia or Alzheimer’s disease. Examples of recommended changes/activities include preforming activities that engage the brain (such as playing games or learning a new skill), keeping physically active and eating a healthy diet that is supplemented with Omega 3 fatty acids (found in fish and certain nuts). While there is not conclusive evidence on whether these lifestyle factors can help those who may develop Alzheimer’s disease, all these factors presented have shown to be effective in helping with certain chronic diseases such as heart disease, type II diabetes and obesity. Therefore, on the advice of a physician, it is recommended that at least some of these lifestyle actions be included in some aspect of the individual’s daily routine (especially if they are a senior citizen) for the prevention of a variety of chronic diseases, and also to possibly prevent or delay the onset of Alzheimer’s disease or dementia.

Current Research

Currently, there is a large amount of studies being conducted in order to better understand and find an appropriate treatment for Alzheimer’s disease. While extensive research is being conducted on many aspects of Alzheimer’s disease, two research areas that were recently highlighted include research into potential biomarkers of Alzheimer’s disease and the possibility of creating a vaccine for Alzheimer’s disease.

In a recent research article published in Nature (July 14, 2011), the possibility of using ‘biomarkers’ to help doctors identify patients who may develop Alzheimer’s disease was explored. Biomarkers are biological indications (ie: genes types, proteins in the blood, etc.) whose presence could indicate the patient’s susceptibility to developing particular diseases. Discovering biomarkers for Alzheimer’s disease would help doctor’s diagnose the disease before symptoms appear and help researchers develop a effective drug that can prevent the onset of the disease. At the University of Pennsylvania’s Alzheimer’s Disease Center, hundreds of thousands of blood and cerebral spinal fluid (the fluid that exists in your brain and spine) samples are stored and made available to researchers who are looking into Alzheimer’s disease. These samples along with high-resolution brain scans are vital sources of information for the Alzheimer’s Disease Neuroimaging Initiative, an organization that is devoted to Alzheimer’s research and specifically, identifying potential biomarkers. Currently, research has shown that the presence of a certain amyloid protein or an elevated total level of tau protein could be used to determine an individual’s susceptibility to developing Alzheimer’s disease; with the presence of a special form of tau protein (with additional phosphate groups) serving as the most effective biomarker . Researchers studying biomarkers are hopeful that further tests will show that these biomarkers are accurate and effective at determining ones likelihood of developing Alzheimer’s disease and could soon become standard medical tests that a doctor could perform on an individual who is at risk of developing Alzheimer’s disease.

Some researchers are also exploring the possibility of developing a vaccine for Alzheimer’s disease.  The main goal of a vaccine for Alzheimer’s disease is to utilize the body’s own immune system to attack and destroy the mis-formed proteins that cause the symptoms, such as amyloid proteins. While previous trails of a vaccine did not turn out very promising, recently a group of researchers have found that administering IVIg (intravenous immunoglobulin) to a group of Alzheimer’s patients was effective at improving or stabilizing their symptoms.  IVIg is a treatment that is often used to boost immunity in a patient whose immune system is compromised (often due to genetic reasons or certain diseases). Drug trails are currently being performed on the use of IVIg in the treatment of Alzheimer’s disease and the results could be made available by the end of 2012. One problem with using IVIg as a treatment for Alzheimer’s disease is that patients would require relatively high doses and there is a limited supply of IVIg (as it is obtained from donated blood). In addition, while IVIg has been shown to improve the symptoms in some Alzheimer’s disease patients, the effects are not permanent and can wear off within a couple of months. However, more research into alternative ways of developing and distributing a vaccine for Alzheimer’s disease is being conducted and some believe that an effective vaccine could be developed within the near future.

Links

Alzheimer Society of Canada – http://www.alzheimer.ca/

Alzheimer’s Disease Neuroimaging Initiative – http://www.adni-info.org/

References

“Alzheimer’s Disease Fact Sheet.” National Institute on Aging. July 2011. Web. 12 Sept. 2011. <http://www.nia.nih.gov/Alzheimers/Publications/adfact.htm>.

“Alzheimer’s Disease: Statistics.” Alzheimer Society of Canada – Société Alzheimer Du Canada. Web. 12 Sept. 2011. <http://www.alzheimer.ca/english/disease/stats-intro.htm>.

Schnabel, Jim. “Vaccines: Chasing the Dream.” Nature 475.7355 (2011): S18-19. Print.

Williams, Ruth. “Biomarkers: Warning Signs.” Nature 475.7355 (2011): S5-S7. Print.

Photo Credits

http://www.ahaf.org/alzheimers/about/