Alzheimers

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What is Alzheimer's Disease?

Alzheimer's disease is the most common form of dementia known today. It causes a progressive decline in memory function and other cognitive processes. Patients may have a change in their personality and behavior which could lead them to become violent, suspicous of others, paranoid and to have hallucinations. It is characterized by neurofibrillary tangles and brain plaques which are only detectable at the time of an autopsy.


Who Discovered Alzheimer's Disease and How:

In 1906 a German Physician named Alois Alzhiemer presented the case of a 51 year old patient who was suffering from a rare brain disease at a medical conference (AFA, 2006). After the woman’s death an autopsy was conducted which presented the brain plaques and tangles which are now used as a way to identify and characterize Alzheimer’s


Symptoms

AD is a neurodegenerative disease which is a subtype of dementia (Lippa et al., 2006). A brief synopsis of the characteristics and stages of AD from the Burke Rehabilitation Center as referenced by Casper et al. (1987) gives an overview of the four stages of AD.

Phase I:
• Notice something is not quite right but not sure what
• Person appears less full of life and energy and quick to anger
• Trouble learning, finding words and slowing of reaction time
• Prefers to be in familiar settings

Phase II: • May need help doing some everyday activities
• Insensitive to others
• Can not make decisions easily
• Trouble concentrating

Phase III:
• Obvious that person is ill
• Memory (short term esp.) is failing while distant past is extremely clear
• Needs directions repeated several times
• Not sure of time or place
• Not sure who people are

Phase IV:
• Help required with almost all activities
• Very poor recent memory
• No sense of direction
• Can’t recognize people

While not all patients will suffer from all of these symptoms, nor will they always be in this order of onset, this order is very common.


Mechanism

Symptoms of AD are primarily composed of a “progressive decline in memory function along with other losses in cognition and is characterized by β-amyloid plaques and neurofibrillary tangles” (Lippa et al., 2006, p.37). According to Saladin (2006, p.474) neurofibrillary tangles reside in the neurons and are “dense masses of broken and twisted cytoskeleton.” The plaques appear in the extracellular matrix. The neurodegenerative diseases which cause dementia are caused by damage to neurons (Lippa et al., 2006). These neurons, which produce acetylcholine, break connections to the other neurons and eventually die off (AFA, 2006). When the neurons in the hippocampus die short term memory declines and then when the neurons in the cerebral cortex die language and judgment skills decline. The two halves of the brain share information via the corpus callosum through the firing or non-firing of neurons (Lippa et al., 2006). Inside the corpus callosum lie nerve fibers composed of white matter which is primarily made of myelinated axons. The loss of distal axons and synapsis are the main cause of neurodegenerative diseases. According to Vickers (2002, p.488) “AD is principally a disease that affects the cerebral cortices, including neurons providing connection to, and within, this brain structure.” Vickers (p.488) also explains that there is a hierarchy to the degeneration of the neurons in the brain with “medial temporal lobe/limbic structures such as the amygdala, hippocampus and entorhinal cortex being affected earlier in the disease and typically showing severe damage by latter stages of the disease.” However, Vickers emphasizes that the exact pathway, mechanism and causes of AD are not known.


Current Treatments and Outlook

While there is no cure for Alzheimer’s there have been several possible cures researched. One of these cures is a vaccine using β-amyloid immunogens (Vickers, 2002). The experimental mice subjects developed the plaques but not the neurofibrillary tangles or the neurodegeneration. How the vaccine works is still up for debate. Some researchers point to the antibody as promoting the dissolution of the amyloid while others say it is inhibiting protein aggregation and yet still others say it may cause other immune cells to be stimulated to engulf the debris. This has yet to be thoroughly tested in humans due to fear of the ramifications of stimulating the immune system of the brain. One study was conducted using 80 individuals in order to find the dosage amount necessary and the effects of the vaccine AN-1792. The study was stopped due to the apparent inflammation of the central nervous system.

Four drugs have been approved by the United States Food and Drug Administration for treating mild and moderate AD (AFA, 2006). These drugs are “tacrine (Cognex®), introduced in 1993; donepezil hydrochloride (Aricept®), marketed since 1996; rivastigmine (Exelon®), available since the spring 2000; and galantamine hydrobromide (RazadyneTM-formerly called Reminyl®), approved in February 2001.” One drug, memantine HCl (NamendaTM) was approved in October 2003 for treating moderate and severe AD and it may slow down the rate of decline in mental function.



Current Research

	Brain imaging studies

A recent magnetic resonance imaging (MRI) study by Lippa et al. (2006) showed that AD patients had a reduction in the size of the corpus callosum and there was a correlation between severity of dementia and the rate of atrophy. When MRI’s are compared to electroencephalograms (EEG), studies show a correlation between the size of the corpus callosum and the decreased amount of connectivity between the two hemispheres of the brain. This leads to the suggestion that losing cortical association neurons which travel through the corpus callosum results in AD. A study conducted by Lippa et al. (2006) found rapid production of neuroglial cells (gliosis) in AD patients and not in cognitively normal patients. The amount of gliosis did not correspond to the level of dementia. They suggest this should be studied further as another possible link to the cause of dementia. Holtzman et al. (2005, p.148) gathered data from different studies at a conference on AD and they found a decrease in the concentration of cerebral spinal fluid which occurred just “before the onset of clinical cognitive” symptoms of AD. The exact cause of AD is still unknown (Vickers, 2002).

	Biomarkers

Identifying Alzheimer’s disease can be done qualitatively by examining the patients and identifying any of the symptoms of the disease but, it can also be done using biomarkers. Biomarkers are a relatively new way of looking at the diagnosis and treatment of AD and may now be considered for diagnosing presymptomatic AD patients (Holtzman et al., 2005). Being able to identify biomarkers of AD in normal individuals is a big step toward finding therapies and/or a cure. Genetic biomarkers can result in early detection of the disease and symptom biomarkers can aid in the full diagnosis of individuals already diagnosed with AD. In 1993 a study on genetic markers, reviewed by Holtzman et al., found apoliprotein E polymorphism to be a risk factor for AD and a test was readily made available to the public. The implications of the test were not thoroughly understood so the test was withdrawn from the market and was then later put back on the market with more detailed directions and information about the meaning of the results.



Informational Web Resources

The sites below contain extremely useful information on Alzheimer's Disease
Alzheimer's Association
Alzheimer's Foundation of America
Mayo Clinic


Song About Alzheimer's Disease

Artist/Band: Dixie Chicks
Lyrics for Song: Silent House
Lyrics for Album: Taking The Long Way

These walls have eyes
Rows of photographs
And faces like mine
Who do we become
Without knowing where
We started from

It's true I'm missing you
As I stand alone in your room
Everyday that will pass you by
Every name that you won't recall
Everything that you made by hand
Everything that you know by heart

And I will try to connect
All the pieces you left
I will carry it on
And let you forget
And I'll remember the years
When your mind was clear
How the laughter and life
Filled up this silent house

One room
Two single beds
In the closet hangs
Your favorite dress
The books that you read
Are in scattered piles
Of paper shreds

Everything that you made by hand
Everything that you know by heart

And I will try to connect
All the pieces you left
I will carry it on
And let you forget
And I'll remember the years
When your mind was clear
How the laughter and life
Filled up this silent house
Silent house

In the garden off the living room
A chill fills the air
And the lilies bloom

And I will try to connect
All the pieces you left
I will carry it on
And let you forget
And I'll remember the years
When your mind was clear
How the laughter and life
Filled up this

And I will try to connect
All the pieces you left
I will carry it on
And let you forget
And I'll remember the years
When your mind was clear
How the laughter and life
Filled up this silent house
Silent house


References

Alzheimer’s Foundation of America, www.alzfdn.org , retrieved October 25, 2006.

Casper, K., and Woerner, L., (1987). Alzheimer’s care: A home health model. The American Journal of Alzheimer's Care and Research. 23-29

Holtzman, D.M., Kantarci, K., Kaye, J., Morris, J. C., Siemers, E.R., Quaid, K. A., and Reiman, E.M., (2005). Role of biomarkers in studies of presymptomatic Alzheimer’s disease. Alzheimer’s & Dementia, 141-151.

Lippa, C. F., MD, Murray, C., and Viehman, A., (2006). The corpus callosum in Pick’s disease, Alzheimer’s disease and Amyotropic Lateral Sclerosis: Gliosis implies possible clinical consequence. American Journal of Alzheimer’s Disease and Other Dementias, 21(1), 37-43.

Saladin, K. S., (2006). The unity of form and function. McGraw-Hill, New York, New York.

Vickers, J. C., (2002). A vaccine against Alzheimer’s disease: Developments to date. Drugs Aging, 19(7), 487-494.