Running head: DISCOVERING ALZHEIMERS DISEASE

Discovering Alzheimers Disease

Courtney Nance
Dixie State University

DISCOVERING ALZHEIMERS DISEASE

Abstract
This paper covers the pathology findings of Alzheimers disease (AD) and presents the
diagnostic studies being explored. Alzheimers is a dementia causing disease affecting many
people, sometimes unknown in early stages. It changes the identity of an individual which
creates hardships on family, friends, and caretakers. Many caretakers are family members
managing the illness until death. Symptoms usually are undiagnosed until late stages of
Alzheimers disease. Throughout history many advances in technology have improved
diagnostic exams. Increased awareness of AD has also helped to increase research.
Neuroimaging studies through biomarkers are being researched to discover the starting cause of
the illness. Magnetic resonance imaging (MRI), computed tomography (CT), functional MRI
(fMRI), positron emission tomography (PET), and fluorodeoxyglucose (FDG)-PET are brain
imaging studies being used. The disease progresses through time, and medication only helps
slow the development. Treatment for Alzheimers disease is not a cure, due to the exact cause
being unknown. Advancements are ongoing which will lead to accurate diagnosis and treatment.

DISCOVERING ALZHEIMERS DISEASE

Discovering Alzheimers Disease

Introduction
Alzheimers disease leads to irreversible changes in brain cells if not detected early.
According to the Alzheimers Association (2014), over five million Americans are living with
Alzheimers and other dementias resulting to one in every three seniors dying with the disease.
In 2013 there were 140,000 care givers to Alzheimers disease (AD) in Utah with 159,000
unpaid hours of care (Alzheimer's Association, 2014). Theories for exact cause and diagnosis of
the illness are still being found. Many of these are through neuroimaging studies. Alzheimers is
becoming more recognized as a disease rather than a sign of old age. This realization has
increased clinical trials to improve diagnosis. Treatment for the illness is just for management,
while many diagnostic studies are being researched.
History
Shown in Figure 1, Dr. Alois Alzheimer, a German physicist,
founded the research to this dementia causing disease by relating
symptoms to microscopic brain changes. According to Kowall (2011), 51
year old Auguste D was brought by her family to Dr. Alzheimer in 1901
(Figure 1). She showed symptoms of memory problems, suspicions of
husband being unfaithful, and difficulty speaking and understanding
speech. Auguste D. passed in 1906 being named the first patient known
Figure 1.
Dr. Alois Alzheimer
and Auguste D.
(Alzheimer's
Association, 2014)

with Alzheimers disease. An autopsy by Dr. Alzheimer determined

dramatic shrinking and abnormal deposits in and around nerve cells in
the brain. He later published his findings in 1907. By 1910, Emil

DISCOVERING ALZHEIMERS DISEASE

Kraepelin, a psychiatrist, noted his work and proposed the disease be named Alzheimers.
Advances in 1931 lead to invention of the electron microscope that magnified up to one million
times. This allowed scientists to study brain cells more in detail. Researchers made the first
validated measurement scale for brain cognitive and functional decline in 1968 to compare level
of impairment with number of brain lesions and tissue damage volume. By 1980 the Alzheimers
Foundation was founded. Alzheimers Disease Day was created on September 21, 1994 due to
President Ronald Regan announcing his diagnosis of the disease. In April 2011 the stages of
Alzheimers criteria were established helping with treatment (Alzheimer's Association, 2014).
Original criteria involved physicians clinical judgment, cognitive testing, and neurological
assessment.
Condition Analysis
Alzheimers disease is a type of dementia involving a progressive brain disorder that
destroys brain cells leading to memory loss, changes in thinking, and behavior (Kowall &
Budson, 2011). It occurs in 60-80 percent of dementia cases and is the sixth leading cause of
death in the United States (Wolk, 2014). Other types of dementia include: vascular dementia,
dementia with Lewy bodies, Parkinson's disease, Creutzfeldt-Jakob disease, Huntington's
disease, normal pressure hydrocephalus and Wernicke-Korsakoff Syndrome. A main
misconception about Alzheimers is that it is a normal part of aging. It is common to have
occasional memory problems like losing keys, but for individuals with Alzheimers the brain
cells malfunction and die. This can cause long term memory problems such as forgetting the
name of a husband or wife. Alzheimers disease has no survivors. Once the brain cells die it
causes loss of body functions making a slow and painful death thus taking away a persons
identity.

DISCOVERING ALZHEIMERS DISEASE

Cause
Formations of plaques, tangles, loss of brain
cell connection, inflammation, and cell death are
objective signs of Alzheimers. Cells communicate
with each other at neuron synapses transferring
electrical signals to form memories, thoughts, and
feelings. Beta-amyloid protein is formed when a larger
protein, found in the fatty membrane surrounding nerve

Figure 2.
Beta-amyloid and Tau Progression
in Alzheimers disease.
(Alzheimer's Association, 2014)

cells, is cut down by enzymes. This protein becomes toxic, is chemically sticky and gradually
bonds together to form plaque that blocks cell signaling at the synapse. The disabled cell then
triggers an immune response of inflammation that demolishes it. Beta-amyloid plaques also
create tangles in proteins called tau that connect cell transport systems. With Alzheimers disease
neurofibrillary tangles of tau eventually break and dont allow nutrients to pass through cells.
This loss of cell connection permits cell death and brain tissue shrinkage (Figure 2). Plaques and
tangles first spread through the brains medial temporal lobe containing the hippocampus
responsible for learning, memory, thinking, and planning. The deposits continue to progress over
time impairing an individuals ability to function in daily life, ultimately causing death.
Stages
Initially two of the following mental functions must be impaired to first be classified as
dementia: memory, communication, focus ability, reasoning/judgment and/or visual perception.
The National Institute on Aging (NIA) and Alzheimers Association have now refined the
previously broad stages of Alzheimers disease to better diagnose and treat the illness, improve

DISCOVERING ALZHEIMERS DISEASE

autopsy reporting, and establish research guidelines for early detection. The stages are preclinical
AD, mild cognitive impairment (MCI) due to AD, and dementia due to AD (Alzheimer's
Association, 2014). In preclinical Alzheimers dementia there are measurable changes in
biomarkers years before noticeable symptoms occur. Stage 2, MCI due to Alzheimers is slight
measurable changes in memory abilities that have noticeable symptoms, but dont affect the
ability to carry out everyday activities. There are four levels of criteria for MCI, but all have not
been established due to the need for further biomarker research. Dementia due to AD, the third
stage, is memory, thinking, and behavioral symptoms that impair the ability to function in daily
life. This criteria used by practitioners today is broad and flexible due to lack of official
biomarkers.
Risks and Prevention
Age, family history, environmental factors, and heredity are all risk factors of AD. The
majority of people with Alzheimers disease are 65 and older, but early onset AD can occur in
ages 30-40 (Wolk, 2014). A disease with heredity develops either through risk genes (increasing
possibility of disease) or deterministic genes (guaranteeing disease). Risk gene apolipoprotein Ee4 (APOE-e4) increases the possibility of developing Alzheimers; whereas deterministic genes
(genes coding amyloid precursor protein, presenilin-1 and presenilin-2) ensure development of
the illness. This is referred to as autosomal dominant Alzheimers disease (ADAD) or familial
Alzheimers disease (FAD) when multiple generations are affected. FAD usually starts in age
30-40 (Alzheimer's Association, 2014). Other preventable risks linked to AD are anything that
damages blood vessels supplying the brain. Life style choices such as smoking, unhealthy diet,
and no exercise all influence blood flow through the brain increasing risk of Alzheimers.

DISCOVERING ALZHEIMERS DISEASE

Partridge (2009) suggests, all these factors are manageable through an improved diet or drug
intervention to adjust circulatory system cholesterol and fat levels.
Signs and Symptoms
Weiner (2012) identifies different cognitive impairment areas due to Alzheimers disease.
Memory, the first noticeable symptom, can be detected through testing in the preclinical phases
of AD. Signs of memory loss affect learning, knowledge deficits, and repetitive actions.
Orientation loss becomes apparent through time and spatial disorientation. Another affected area
is language, such as finding it hard to remember words and poor speech content. Ideomotor
apraxia, difficulty translating an idea into action, becomes common in more severe stages of the
disease. Visual processing is another symptom through low object or person recognition, spatial
confusion, and small attention span. Sundowning is a unique effect that increases confusion and
behavioral symptoms in the afternoon and evening hours. Another sign is executive dysfunction
through poor planning/judgment and inability to complete complex tasks.
Diagnosis through Biomarkers
Physicians are able to diagnose general dementia through medical history, physical
examination, and characteristic changes in function and behavior. However, it is hard to
determine the exact cause of dementia. Other reasons such as depression, medication side effects,
alcohol excess, thyroid problems, vitamin deficiencies, and stroke can all cause memory
problems that are treated differently than Alzheimers. Once dementia is diagnosed, there is not
one test that can determine Alzheimers disease. The next step is to define the cause through
neuroimaging. Studies through biomarkers are being used to determine if the cause of dementia
is due to AD. Biomarkers, short for biological markers, are things in the body that can be

DISCOVERING ALZHEIMERS DISEASE

measured and reliably show disease presence, disease absence, or risk development. The
strongest biomarkers candidates being researched today are proteins in cerebrospinal fluid (CSF),
genetic risk profiling, and neuroimaging studies using magnetic resonance imaging (MRI) or
positron emission tomography (PET) (Alzheimer's Association, 2014).
CSF Biomarkers
Proteins that are prevalent in Alzheimers are beta-amyloid and tau. Cerebrospinal fluid
levels of these proteins found in early AD can help individuals take precautions. People with
abnormal levels can be candidates for clinical trials and treatments to help slow progression.
Gene Biomarkers
When Alzheimers is diagnosed in ages 30-60 it is usually genetically caused through
Familial Alzheimers Disease. According to the National Institute on Aging (2012), this earlyonset is caused by mutation in one of three genes inherited from a parent that causes abnormal
proteins to be formed. A child with at least one parent that carries the mutation of FAD has a
50/50 chance of developing the illness (National Institute on Aging, 2012). APOE-e4 is the
strongest risk gene biomarker used to identify Alzheimers. Identifying risk genes does not
confirm the disease, but can lead to further tests for treatment.
Neuroimaging Biomarkers
Structural imaging biomarkers are brain structure changes visible using magnetic
resonance imaging and computed tomography (CT). The tests help rule out other conditions
causing symptoms similar to Alzheimers. Identifying preclinical AD though imaging also helps
researchers to develop treatments to slow or stop the disease. The brains cortical thinning and
hippocampus shrinking are signature signs being researched for the official cause of AD. For

DISCOVERING ALZHEIMERS DISEASE

example, figure 3 shows the initial assessment (top row)

compared to six years later (bottom row) displaying
progressive focal frontal atrophy caused by
frontotemporal dementia (FTD). FTD causes
hippocampal atrophy, a main sign of Alzheimers
(Weiner & Lipton, 2012). MRI is preferred over CT for
displaying better resolution and contrast for gray matter
and white matter hyper intensities, and better coronal and
Figure 3.
MRI Images of Frontal Atrophy.
(Weiner & Lipton, 2012)

sagittal views of small brain areas important for

cognition, such as the hippocampus. Structural imaging

biomarkers are limited at times by not being able to determine the exact cause of atrophy, so
molecular imaging is then used.
Functional imaging biomarkers use functional MRI (fMRI) and fluorodeoxyglucose
(FDG)-PET to monitor brain cell activity. The emerging method fMRI has helped determine
anatomical correlation in the medial temporal lobe to abnormal cognitive function with AD by
imaging blood flow in response to a memory task or in resting state. FDG -PET also uses task
oriented exams that show associations with Alzheimers and decreased glucose metabolism in
brain areas of memory or problem solving. This study helps distinguish between similar diseases
and increase diagnostic accuracy. For example, in frontotemporal disease hypometabolism is
greater in anterior region which is opposite from Alzheimers.
Molecular imaging biomarkers use positron emission tomography to display the brains
chemistry and function to confirm molecular changes due to beta-amyloid and tau deposits
destroying brain cells. PET works by injecting patients with a radioisotope specific to the

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possible disease which travels to the problem area emitting gamma rays intercepted by detectors
that produce an image. This imaging biomarker is beneficial by determining preclinical AD
before the brain changes in structure or function. PET has been approved my Medicare as a
diagnostic procedure to differentiate between frontotemporal dementia and Alzheimers disease
(Weiner & Lipton, 2012). In 2012-2014 the U.S. Food and Drug Administration approved three
molecular imaging tracers for patients being evaluated with Alzheimers disease (Alzheimer's
Association, 2014). Tracers florbetapir F-18, flutametamol F-18, and florbetaben F-18 bind to
beta-amyloid revealing plaques in the brain. Although amyloid plaques are characteristic of AD,
they cannot diagnose the disease because many live with this plaque buildup and experience no
symptoms. Table 1 displays progression of AD and at which stage each biomarker is helpful in
detecting either preclinical AD, MCI due to AD, or Alzheimers due to dementia. Although

Table 1.
Alzheimers Disease Biomarkers.
(National Institute on Aging, 2012)

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biomarkers are in need of further research, the importance of detecting preclinical AD before
symptoms occur can lead to accurate diagnosis and treatment before more damage spreads
through the brains cortex.
Treatment
Many advanced treatment techniques are under research and clinical trials today.
Medicine is available for individuals to help slow progression of Alzheimers disease. The FDA
has approved cholinesterase inhibitors and memantine to treat cognitive symptoms (Alzheimer's
Association, 2014). Both medications help prevent breakdown of chemical messengers important
for learning and memory. They also help worsening of symptoms temporarily. Many physicians
also prescribe high vitamin E doses, which is an antioxidant to protect brain cells from
breakdown. Medications for behavior and sleep changes are also available, but non-drug
approaches are recommended first such as communication and coping tips for the caretakers to
help.
Conclusion
Alzheimers disease is an illness that affects the individual, family, friends, and
caretakers. In 2012, cost of caring for people with AD (keeping in mind family members who
care for free) in the United States was estimated at two hundred billion dollars (Wolk, 2014).
Diseases that affect brain function are difficult to see as an illness. Many consider memory
problems as a normal part of aging. However, early detection of AD can help with a better
lifestyle by preventing permanent changes in brain cell death. MRI and CT brain scans can lead
to structural changes characteristic of AD. Tests should not conclude there. PET gives more
specific landmarks as to where the disease has spread to, via the beta-amyloid plaques and tau

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tangles. CSF, gene, and neuroimaging biomarkers are leading the way for correct diagnosis but
still lack specificity. Treatment to help slow AD progression is available along with many nondrug methods. Through more research and technology advancements Alzheimers disease
treatment will improve with hope of leading to a cure.

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References
Alzheimer's Association. (2014, November). What is Alzheimer's? Retrieved November 11,
2014, from Alzheimer's Disease & Dementia | Alzheimer's Association:
http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp
Kowall, N. W., & Budson, A. E. (2011). Handbook of Alzheimer's Disease and Other
Dementias. Hoboken, NJ, USA: Wiley-Blackwell.
National Institute on Aging. (2012). A Primer on Alzheimer's Disease and the Brain. Retrieved
November 14, 2014, from National Institute on Aging:
http://www.nia.nih.gov/alzheimers/publication/2011-2012-alzheimers-disease-progressreport/primer-alzheimers-disease-and#diagnosed
Partridge, K. (2009). The Brain. Dublin, New York: H.W. Wilson Co.
Weiner, M. F., & Lipton, A. M. (2012). Clinical Manual of Alzheimer Disease and Other
Dementias. Arlington, VA, USA: American Psychiatric Publishing.
Wolk, D. A. (2014, March 7). MCI to Dementia: Imaging Biomarkers in Clinical Practice.
Diagnosing Alzheimer's Disease.