UNIVERSITY OF ALGIERS

YEAR:2015/2016

ACADEMIC

FACULTY OF LANGUAGES

3LMD GROUP 05

DEPARTEMENT OF ENGLISH

ALZHEIMERS
RESEARCH PAPE

ABSTRACT

ABSTRACT

The present research has two aims. First, to create a

preliminary behavioral profile

Contents
-Introduction
-History
-Signs ans symptoms
-Causes
-Pathophysiology
-Diagnosis
-Prognosis
-Epidemology
-Conclusion

Alzheimers disease

Alzheimers disease is a chronic neurodegenerative

disease that usually starts slowly and gets worse over
time. The most common early symptom is difficulty
remembering recent events (memory loss). As the
disease advances, symptoms can include problems with
language, disorientation (including easily getting lost),
mood swing, loss of motivation, not managing self-care,
and behavioral issues. As a persons condition declines,
they often withdraw from family and society. Gradually,
bodily functions are lost, ultimately leading to death.
Although the speed of progression can vary, the average
life expectancy following diagnosis is three to nine years.
The cause of Alzheimer, disease is poorly understood.
About 70% of the risk is believed to be genetic with many
genes usually involved. Other risk factors include a
history of head injuries, depression, or hypertension. The
disease process is associated with plaque and tangles in
the brain. A probable diagnosis is based on the history of
the illness and cognitive testing with medical imaging and
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blood tests to rule out other possible causes. Initial

symptoms are often mistaken for normal aging.
Examination of brain tissue is needed for a definite
diagnosis. Mental and physical exercise and avoiding
obesity may decrease the risk of AD. There are no
medications or supplements that decrease risk.

History

The ancient Greek and Roman philosophers and physician

associated old age with increasing dementia. It was not
until 1901 that German psychiatrist Alois Alzheimer
identified the first case of what became known as
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Alzheimers disease in a fifty-year-old woman he called

Auguste D. He followed her case until she died in 1906,
when he first reported publicly on it. During the next five
years, eleven similar cases were reported in the medical
literature, some of them already using the term
Alzheimers disease. The disease was firast described as a
distinctive disease by Emil Kraepelinafter suppressing
some of the clinical (delusions and hallucinations) and
features (arteriosclerotic changes) contained in the
original report of Auguste D. He included Alzheimers
disease, also published presenile dementia by Kraepelin,
as a subtype of senile dementia in the eighth edition of
his Textbook of Psychiatry, published on July,15,1910.
For most of the 20th century, the diagnosis of Alzheimers
disease was reserved for individuals between the ages of
45 and 65 who developed symptoms of dementia. The
terminology changed after 1977 when a conference on AD
concluded that the clinical and pathological
manifestations of presenile and senile dementia were
almost identical, although the authors also added that
this did not rule out the possibility that they had different
causes. This eventually led to the diagnosis of Alzheimers
disease independent of age. The term senile dementia of
the Alzheimer type (SDAT) was used for a time to describe
the condition in those over 65, with classical Alzheimers
disease being used to describe those who were younger.
Eventually, the term Alzheimers disease was formally
adopted in medical nomenclature to describe individuals
of all ages with a characteristic common symptom
pattern, disease course, and neuropathology.

Signs and symptoms

The disease course is divided into four stages, with a

progressive pattern of cognitive and functional
impairment.
Effects

of ageing on memory:
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-Forgetting things occasionally

-Misplacing items sometimes
-Minor short-term memory loss
-Not remembering exact details
Early stage Alzheimers:

-Not remembering episodes of forgetfulness

-Forgets names of family or friends
-Changes may only be noticed by close friends or
relatives
-Some confusion in situations outside the familiar
Middle stage Alzheimers:

-Greater difficulty remembering recently learned

information
-Deepening confusion in many circumstances
-Problems with sleep
-Trouble knowing where they are
Late stage Alzheimers:

-Poor ability to think

-Repeats same conversations
-More abusive, anxious, or paranoid
-Problems with speaking

Causes
The cause for most Alzheimers cases is still mostly
unknown except for 1% to 5% of cases where genetic
differences have been identified.
Genetics:

The genetic heritability of Alzheimers disease based on

reviews of twin and family studies, range from 49% to
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79%. Around 0.1% of the cases are familial forms of

autosomal (not sex-linked) dominant inheritance, which
have an onset before age 65. This form of the disease is
known as early onset familial Alzheimer disease. Most of
autosomal dominant familial AD can be attributed to
mutation in one of three genes: those encoding amyloid
precursor protein (APP) and presenilins 1and 2. Most
mutations in the APP and presenilin genes increase the
production of a small protein called A42, which is the
main component of senile plaques. Some of the mutations
merely alter the ratio between A40-without increasing
A42 levels. This suggests that presenilin mutations can
cause disease even if they lower the total amount of A
produced and may point to other roles of presenilin or a
role for alterations in the function of APP and/or its
fragments other than A. There exist variants of APP which
are protective.
Most cases of Alzheimer disease do not exhibit
autosomal-dominant inheritance and are termed sporadic
AD and genetic differences may act as risk factors is the
inheritance of 4 allele of the Apolipoprotein E (APOE).
Between 40% and 80% of people with AD possess at least
one APOE 4 allele. The APOE 4 allele increases increases
the risk of the disease by three times in heterozygotes
and by 15 times in homozygotes. Like many human
disease, environmental effects and genetic modifiers
result in incomplete penetrance. For example, certain
Nigerian populations do not show relationship between
dose of APOE 4 and incidence or age-of-onset for
Alzheimers disease seen in other human populations.
Early attempts to screen up to 400 candidates genes for
association with late-onset sporadic AD (LOAD) resulted in
a low yield. More recent genome-wide association studies
(GWAS) have found 19 areas in genes that appear to
affect the risk. These genes include: CASS4, CELF1,
FERMT2,HLA-DRB5, INPP5D, NME8, PTK2B, SORL1,
ZCWPW1, SIC24A4, CLU, PICALM, CR1, BIN1, MS4A,
ABCA7, EPHA1, and CD2AP.

Mutations in the TREM2 gene have been associated with a

3 to times higher risk of developing Alzheimers disease.
A suggested mechanism of action is that when TREM2 is
mutated, white blood cells in the brain are no longer able
to control the amount of beta amyloid present.

Cholinergic hypothesis:

The oldest, on which most currently available drug

therapies are based , is the cholinergic hypothesis has not
maintained widespread support? Largely because
medications intended to treat acetylcholine deficiency
effects have no also been proposed, for example,
initiation of large-scale aggregation of amyloid, leading to
generalized neuroinflammation.

Other hypotheses:

A neurovascular hypothesis has been proposed which

state that poor functioning of the blood brain barrier may
be involved.
The cellular homeostasis of biometals such as ionic
copper, iron, and zinc is disrupted in AD though it remains
unclear whether this is produced by or causes the
changes in proteins. These ions affect and are affected by
tau, APP, and APOE, and their dysregulation may cause
oxidative stress that may contribute to the pathology
.Some studies have shown an increased risk of developing
AD with environmental factors such as the intake of
metals, particularly aluminium.
Smoking is a significant AD risk factor. System markers of
the innate immune system are risk for late-onset AD.
There is tentative evidence that exposure to air pollution
may be a contributing factor to the development of
Alzheimers disease.

An infection with Spirochetes (a bacteria) in gum disease

may cause dementia and may be involved in the
pathogenesis of Alzheimers disease

Pathophysiology

There is cortical atrophy in Alzheimers Disease,

associated
with loss of gyri and sulci in the temporal lobe and
parietal
lobe , and parts of the frontal cortex and cingulate gyrus.

Neuropathology:

Alzheimers disease is characterized by loss of neurons

and synapses in the cerebral cortex and certain
subcortical regions. This loss results in gross atrophy of
the affected regions, including degeneration in the
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temporal lobe and parietal lobe, and parts of the frontal

cortex and cingulate gyrus. Degeneration is also present
in brainstem nuclei like the locus coeruleus. Studies using
MRI and PET have documented reduction in the size of
specific brain regions in people with AD as they
progressed from mild cognitive impairment to Alzheimers
disease, and in comparison with similar images from
healthy older adults.

Both amyloid plaques and neurofibrillary tangles are

clearly visible by microscopy in brains of those afflicted by
AD. Plaques are dese, mostly insoluble deposits of betaamyloid peptide and cellular materials outside and around
neurons. Tangles (neurofibrillary tangles) are aggregates
of the microtubule-associated protein tau which has
become hyperphosphorylated and accumulate inside the
cells themselves. Although many older individuals
develop some plaques and tangles as a consequence of
ageing, the brains of people with AD have a greater
number of them in specific brain regions such as the
temporal lobe. Lewy bodies are not rare in the brains of
people with AD.

Diagnosis

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Alzheimers disease is usually diagnosed based on the

persons

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