Alzimer Disease

B.
Pharma Part IV, (2008)
Alzheimers Disease
INTRODUCTION
Alzheimers disease is a disorder of memory. The term memory implies two capabilities, the
capacity to recall past or residual information and the capacity to absorb and retain new
information. Memory may be lost quit suddenly, as in an acute confusional state, or insidiously as
in a progressive dementia.
The term dementia implies a generalized, progressive loss of intellectual function and
memory. Alzheimers disease which is most common form of dementia among older people
considered as a type of progressive dementia. It is a chronic, progressive, degenerative
cognitive disorder that accounts for more than 60% of all dementias. There is a two types AD.
1. Senile type (Fund in people over 65)
2. Presenile type (b/w the ages of 40 to 60)
Alzheimers disease is a brain disorder that seriously affects a persons ability to carry out
daily activities which involve the parts of the brain that control thought, memory, and
language.
AD is named as described in history after Dr. Alois Alzheimer a German doctor. In 1906, Dr.
Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental
illness. He found abnormal clumps (amyloid plaques) and tangled bundles of fibers
(neurofibrillary tangles).
These plaques and tangles in the brain are considered signs of AD.
Scientists also have found other brain changes in people with AD. Nerve cells die in areas of
the brain that are vital to memory and other mental abilities. There also are lower levels of
Maharishi Arvind Institute Of Pharmacy, Jaipur
B. Pharma Part IV, (2008)
Alzheimers Disease
some of the chemicals in the brain that carry messages back and forth between nerve cells.
AD may impair thinking and memory by disrupting these messages.
Alzheimers disease (AD) is a neuropathological process which progressively and relentlessly
devastates the brains of its victims. The AD pathology produces progressively more severe
deficits in cognition, behavior, and activities of daily living over a time course of
deterioration averaging 8 years. Most of the studies of AD pathology have examined the
composition and distribution of the neurofibrillary tangles and senile plaques first described
by Alois Alzheimer in 1907. However, Alzheimers first comments on this disease referred to
the psychosocial disruption which he found in his patient. To solve this disease, the
psychosocial clinical problems and the neurobiological system dysfunction must be defined
to the point that they indicate what neuromolecular mechanisms are attacked by the AD
process.
The AD process has no direct effects on most functions of the body and is restricted in its
attack on the brain. Investigations in to the biology of AD have yet to reveal the basis of this
process. Clearly the most important factor associated with the development of AD is age,
with AD changes appearing in many individuals at a young age and developing in a majority
of individuals as age progresses past 60 years. studies of family constellation, DNA
polymorphisms. And genetic mechanisms have revealed that genetic factors play a significant
role in predisposing some individuals to developing AD. Certain environmental factors,
including a possible contribution by aluminum, may also influence the onset of the disease.
However, a major concern understands which neuronal systems in the brain are affected by
the AD process, and how their unique physiological processes may predispose them to allow
the progressive development of this disease process.
Alzheimers Disease
The affected neurobiological systems seem to be those which underlie learning, and the AD
process appears to attack mechanisms for storing new information from molecular biological
machinery, to specific neurotransmitter systems to macroscopic anatomical structures of the
cerebrum. Through more complete understanding of the attack of the AD process, it is hoped
that approaches can be developed to prevent or slow the development of Ad.
So we can say that Alzheimers disease is the term used to describe a dementing disorder
marked by certain brain changes, regardless of the age of onset. Alzheimers disease is nor a
normal part of aging it is not something that inevitably happens in later life. Rather, it is one
of the dementing disorders, a group of brain diseases that lead to the loss of mental and
physical function.
Although Alzheimers disease is not curable or reversible there are ways to alleviate
symptoms and suffering and to assist families. Not every person with this illness must
necessarily move to a nursing home. Many thousands of patients especially those in the early
stages of the disease are cared for by their families in the community. Indeed one of the most
important aspects of medical management is family education and family support services.
When, or whether, to transfer a patient to a nursing home is a decision to be care fully
considered by the family.
Cross Section Area of Brain Which Affects In AD: -
Alzheimers Disease
These images represent a cross section of the brain as seen from the front. The cross section
on the left represents a brain from a normal individual and the on the right represents a brain
with Alzheimers These images represent a cross section of the brain as seen from the front.
The cross section on the left represents a brain from a normal individual and the on the right
represents a brain with Alzheimers disease.
In Alzheimers disease, there is a an overall shrinkage of brain tissue. The grooves or furrows
in the brain called sulci (plural of sulcus), are noticeably widened and there is shrinkage of the
gyri (plural of gyrus), the well-developed folds of the brains outer layer In addition, the
ventricles, or chambers within the brain that contain cerebrospinal fluid, are noticeably
enlarged. In the early stages of Alzheimers disease, short- term memory begins to decline (box
labeled memory) when the cells in the hippocampus, which is part of the limbic system,
degenerate. The ability to perform routine tasks also declines. as Alzheimers disease spreads
through the cerebral cortex (the outer layer of the brain),
Judgment declines, and emotional outbursts may occur and language is impaired. Progression
of the disease leads to the death of more nerve cells and subsequent behavior changes, such as
wandering and agitation. The ability to recognize faces and to communicate is completely lost
Alzheimers Disease
in the final stages .Patients lose bowel and bladder control, and eventually need constant care.
This stage on complete control, and eventually need constant care. This stage on complete
dependency may last for years before the patient dies. The average length of time from
diagnosis to death is 4 to 8 years, although it can take 20 years or more for the disease to run its
course.
One of the hallmarks of Alzheimers disease is the accumulation of amyloid plaques between
nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the
body produces normally. Beta - amyloid precursor protein (APP). In a healthy brain, these
protein fragments would be broken down and eliminated. In Alzheimers disease, the fragments
accumulate to form hard insoluble plaques.
Alzheimers Disease
Neurofibrillary tangles consist of insoluble twisted fibers that are found inside of the brains
cells. They primarily consist of a protein called tau, which forms part of a structure called a
microtubule. The microtubule helps transport nutrients and other important substances from
one part of the nerve cell to another (the axon is the long threadlike extension that conducts
nerve impulses away from the body of a nerve cell, and dendrites are any of the short branched
threadlike extensions that conduct nerve impulses towards the nerve cell body. In Alzheimers
disease the tau protein is abnormal and the microtubule structures collapse.
There is an overall shrinkage of brain tissue as Alzheimers disease progresses In addition, the
Ventricles, or chambers within the brain that contain cerebrospinal fluid, ar4e noticeably
enlarged. In the early stages of Alzheimers disease, short-term memory begins to decline when
the cells in the hippocamus, which is part of the limbic system, degenerate. The ability to
perform routine tasks also declines. As Alzheimers disease spreads through the cerebral
cortex (the outer layer of the brain), judgment declines, and emotional outbursts may occur and
language is impaired. Progression of the disease leads to death of mare nerve cells and
subsequent behavior changes, such as wandering and agitation. The ability to recognize faces
and to communicate is completely lost in the final stages. Patients lose bowel and bladder
control, and eventually need constant care. This stage of complete dependency may last for
years before the patient dies. The average length of time from diagnosis to death is 4 to 8 years,
although it can take 20 years or more for the disease to run its course.
Alzheimers Disease
HISTORY
In 1901, a 51 - year- old woman August D, was admitted to the state asylum in Frankfurt. She
was suffering from cognitive and language dificits, auditory hallucinations, delusions,
paranoia and aggressive behaviour, and was studied by Alois Alzheimer (1864-1915), a
doctor at the hospital.
Alzheimer moved to the Munich medical school in 1903 to work with Emil Kraepelin - one
of the foremost German psychiatrists of that era-and when Auguste D died in April 1906, her
brain was sent to him for examination. In November of that year, Alzheimer presented
Augustes case at a psychiatry meeting, and he published his talk in 1907.
He lectured about Augustes who had died after years of experiencing severe memory
problems, confusion, and difficulty understanding question. Upon her death, he performed an
autopsy on her brain and described dense deposits outside and around the nerve cells (neuritic
plaques). Inside the nerve cells he noted the presence of twisted bands of fibers
(neurofibrillary tangles). Today, this degenerative brain disorder bears his name. The
observation of the plaques and tangles at autopsy is still required to obtain a definitive
diagnosis of Alzheimers disease.
In 1910, Kraepelin coined the term, Alzheimers disease - a term still used to refer to the
most common cause of senile dementia.
Alzheimers Disease
The Concept of Dementia: During the eighteenth century, the term dementia had a clinical and a legal usage, referring to
states of psychosocial imcompetence regardless of age, reversibility or pathological
antecedents. This broad view was gradually narrowed down, culminating at the end of the
nineteenth century with what I have called the cognitive paradigm - The view that dementia
is an irreversible disorder (mainly in the elderly) of intellectual functions (Particularly
memory).
This paradigm is still in place today, although it was partially modified during the 1980s
when it was accepted that non- cognitive features-such as hallucinations, delusions and
behavioral deficits - were part of the disease. Before the adoption of the cognitive paradigm,
such symptoms actually formed part of the definition of senile dementia.
In his original presentation, Alzheimer discussed Auguste Ds cognitive and non-cognitive
deficits, and reported that, on post mortem, he had found plaques, tangles and arteriosclerotic
changes in her brain.
All the markers that Alzheimer reported were well known at the time, and it is clear from his
writings that he never meant to say that they were ne. For example , it was the prevalent view
before 1906 that in senile dementia the destruction of the neurofibrillae appears to be more
extensive than in the brain of a paralytic subject. Indeed, five month before Alzheimers
report, the American worker Fuller - whose contribution to this field has been neglected- had
drown attention to the presence of neurofibrillar bundles in senile dementia.
At the end of the section on senile dementia in the eighth edition (1910) of his Handbook of
Psychiatry, Kraepelin wrote:
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...the autopsy reveals, according to Alzheimers description, changes that represent the most
serious form of senile dementia ..... the Drusen were numerous and almost one -third of the
cortical cells had died off. In their lace instead we found peculiar deeply stained fibrillary
bundles that were closely packed to one another, and seemed to be remnants of degenerated.
Cell bodies .... The clinical interpretation of this Alzheimers disease is still confused. While
the anatomical findings suggest that we are dealing with a particularly serious form of senile
dementia, the fact that this disease sometimes starts already around the age of 40 does not
allow this supposition [i.e. it should be considered as a new disease]. In such cases we should
at least assume a senium praecox if not perhaps a more or less age - independent unique
disease process.
Neither the biological markers nor the symptom constellation reported by Alzheimer were
new, and he was fully aware of it. In fact, states of persistent congnitive impairment affecting
the eldearly, and accompanied by delusions and hallucinations were well known at the time.
A conservative interpretation of the primary data suggests that Alzheimers only intention
was to point out that senile dementia could occur in younger people (in this case, in a woman
of 51). In this regard, Perusini (a man who worked with him) wrote that, for Alzheimer these
morbid forms do not represent anything but atypical form of senile demintia.
A great deal has been learned since the early part of this century concerning the nature of the
plaques and tangles and the brain regions that become affected as the disease progresses. In
addition, scientists are gaining greater insight into the genetic factors contributing to
Alzheimers these morbid forms do not represent anything but atypical form of senile
dementia
Alzheimers Disease
A great deal has been learned since the early part of this century concerning the nature of the
plaques and tangles and the brain regions that become affected as the disease progresses. In
addition, scientist are gaining greater insight in to the genetic factors contributing to
Alzheimers disease, Five genes have now been identified; three of these genes (located on
chromosomes 1, 14 and 21) each contribute to early-onset Alzheimers disease, and two
genes (UBQNLI on chromosome 9 and ApoE4 on chromosome 19) Increase the risk of
developing the disease later in life. Genetic risk factors alone, in most cases, are not enough
to cause the disease, so other risk factors are involved and researchers are actively exploring
them.
In 1993, the FDA approved the first drug to treat Alzheimers disease, Cognex (Tacrine),
which increases the amount of the neurotransmitter acetylcholine in the brain and can slow
cognitive decline. A second drug, Aricept (Donepezil), became available in 1996, and in
2000, the drug exelon (Rivastigmine) was approved by FDA. A fourth drug Razadyne
(Galntamine) was approved in early 2001. Cognex, Aricept, Exelon and Reminyl work by
increasing the amount of acetylcholine available in the brain. Cognex though effective, has
more adverse side effects than the other medications. In 1997, studies indicated that vitamin
E and a drug normally used in the treatment of Parkinsons disease, Eldepryl (Selegiline),
were found to be helpful in slowing mental deterioration in patients with moderate
Alzheimers disease however, further studies are necessary to corroborate these findings. In
2003 , the FDA approved the first drug to treat moderate to severe Alzheimers disease.
Namenda is an NMDA receptor antagonist, and appears to protect the brains nerve cells
against excess amounts of glutamate, a messenger chemical released in large amounts by
cells damaged by this devastating neurological disease.
Alzheimers Disease
Although the diagnosis of Alzheimers can still only be made through an autopsy, clinicians
can now make an accurate diagnosis 90 % of the time by taking a history, performing a
physical examination, utilizing medical tests, ruling out other causes, and measuring memory
capabilities and psychological status. Early diagnosis is important because the treatments that
are available work best at the earliest stages of the disease.
There is no known treatment that will cure Alzheimers disease. For those who are currently
suffering with the disease, medications can only help control symptoms and/or slow the
progression of the disease.
Alzheimers Disease
ANATOMY OF BRAIN
In Alzheimers disease brain is affected by which working of the brain is disturbed which
results in improper functioning of the brain. To understand the AD it is necessary that first of
all discussing about the anatomy of brain.
Anatomy: Brain is the large soft mass of nerve tissues contained within the cranial; the cranial portion
of the central nervous system. The brain is composed of neurons and neuralgia of supporting
cell. The brain is consist of gray and white matter. Gray matter is composed mainly of neuron
cell bodies and is concentrated in the cerebral cortex and the nuclei and basal ganglia. White
matter is composed of axons. Which form tracts connecting parts of the brain with each other
and with the spinal cord.
The brain is consisting of the three major parts; the cerbrum, cerebellum, and brainstem
(medulla, pons, and mid brain).
Alzheimers Disease
The image on the left is the outside of the brain, viewed from the side, showing the major
lobes (frontal, parietal, temporal and occipital) and the brain stem structures (pons, medulla
oblongata, and cerebellum).
The image on the right is a side view showing the location of the limbic system inside the
brain. The limbic system consists of a number of structures, including the fornix,
hippocampus, cingulated gyrus, amygdala, the parahippocampal gyrus and parts of the
thalamus.
The hippocampus is one of the first areas affected by Alzheimers disease. As the disease
progresses, damage extends throughout the lobes. as the damage increases shrinkage of the
frontal or temporal lobes and nerve cell death in several areas of the brain, leading to a loss of
key mental functions such as memory, learning and concentration.
Alzheimers Disease
Amyloid Plaques: One of the hallmarks of Alzheimers disease is the accumulation of
amyloid plaques
between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments
that the body produces normally. Beta-amyloid is a fragment of a protein that is snipped
from another protein called amyloid precursor protein (APP). In a healthy brain, these protein
fragments would be broken down and eliminated. In Alzheimers disease, the fragments
accumulate to form hard, insoluble plaques.
Alzheimers Disease
Neurofibrillary Tangles: Neurofibrillary tangles consist of insoluble twisted fibers that are found inside of the brains
cells. They primarily consist of a protein called tau- which forms part of a structure called a
microtubule. The microtubule helps transport nutrients and other important substances from
one of the nerve cell to another. In Alzheimers disease, however, the tau protein is abnormal
and the microtubule structures collapse.
Alzheimers Disease
CAUSES
The causes of Alzheimers arent well understood. But researchers have found that people
with Alzheimers have brain cells that become damaged and die for unknown reasons. A
healthy brain has about 100 billion nerve cells called neurons. Neurons generate electrical
and chemical signals that are relayed from neuron to neuron to help you think, remember and
feel. Chemicals called neurotransmitters help these signals flow seamlessly between neurons.
Initially in people with Alzheimers neurons in certain locations of the brain begin to die. As
they die, lower levels of neurotransmitters are produced, creating signaling problems in the
brain.
Plaques and Tangles: Alzheimers disease is named after Dr. Alois Alzheimer, a German neurologist. In 190, he
examined the brain of a woman who had died after years of progressive dementia. Her brain
tissue showed abnormal clumps and irregular knots of brain cells. Today, these clumps (now
called plaques) and knots (now called tangles) are considered hallmarks of Alzheimers
disease.
Researchers continue to study these abnormal structures- plaques and tangles- to better
understand why brain cells slowly die in people with Alzheimers. In the meantime, scientists
have theories that may explain how these structures are involved in Alzheimers disease.
Plaques: Maharishi Arvind Institute Of Pharmacy, Jaipur
Alzheimers Disease
Plaques are made up of a normally harmless protein called beta amyloid. Its believed that
deposits of plaques form between neurons early on in the disease process, before neurons
begin to die and symptoms develop. Although the ultimate cause of neuron death in
Alzheimers isnt known, mounting evidence suggests that a form of beta - amyloid protein
may be the culprit. Three genetic mutations- in amyloid precursor protein (APP) and
presenilin 1 (PSI) and presenilin 2 (PS2) proteins- are known to cause a small number of
early-onset forms of Alzheimers disease. These mutations result in the production of amyloid
plaques. Together, these three genetic mutations account for less than 10 percent of all
Alzheimers cases.
Tangles: The internal support structure for brain neurons depends on the normal functioning of a
protein called tau. In people with Alzheimers threads of tau protein undergo alterations that
causethem to become twisted. Many researchers believe this may seriously damage neurons,
causing them to die.
Inflammatory Responses: Researchers have observed inflammation in the brains of some people with Alzheimers
disease. Inflammation is your bodys response to injury or infection and a natural part of the
healing process. Even as betaamyloid plaques develop in the spaces between neurons,
immune cell (microglia) are at work getting rid of dead cells and other waste products in the
brain. Scientist speculate that the microglia may view plaques as foreign substances in the
body and try to destroy them, triggering the inflammatory response. Or the microglia may be
Alzheimers Disease
trying to remove damaged neurons. The microglia may also activate other compounds that
cause inflammation. Although researchers believe the inflammation occurs before plaques
have fully formed, they arent sure how this development relates to the disease process.
Theres also debate about whether inflammation has a damaging effect on neurons or whether
it is beneficial in clearing away plaques.
At first AD destroys neurons (nerve cells) in parts of the brain that control memory, including
the hippocampus, which is a structure deep in the deep that controls short- term memory. As
these neurons in the hippocampus stop functioning, the short term memory of the person
fails, and the ability to perform familiar tasks decreases. Later AD affects the cerebral cortex,
particularly the areas responsible for language and reasoning; these language skills are lost
and the ability to make judgments is changed. Personality changes occur, which may include
emotional outbursts, wandering, and agitation. The severity of these changes increases with
the progression of the disease. Eventually many other areas of the brain become involved, the
brain regions affected atrophy (shrink and lose function), and the person with AD becomes
bedridden, incontinent, helpless, and non responsive.
Alzheimers disease has emerged as one of the great mysteries in modern day medicine, with
a growing number of clues but still no answers as to its cause. The quest to uncover its cause
has the air of a veritable whodunit saga. Though none of the leading theories about the
genesis of Alzheimers disease has resolved the mystery. each has led to certain intriguing
findings that suggest further investigation is needed. It is important to examine these theories,
not only to understand current thinking on Alzheimers disease, but also to learn what popular
ideas have proved to be incorrect. There havebeen at least fie prominent theories about the
cause of Alzheimers disease:
1. Chemical Theories: - (Deficiencies and Toxic Excesses): Maharishi Arvind Institute Of Pharmacy, Jaipur
Alzheimers Disease
A. Biochemical changes in growth (Trophic) factors: -Much research is taking

place in the examination of naturally occurring substances that may affect the nervous
system and that may contribute to the dysfunction or death of brain cells in Alzheimers.
It is possible that one reason for nerve cell death in Alzheimers patients is a decline in
growth promoting factors that maintain the functioning of brain cells, or conversely, a
spontaneous increase in factors that are toxic to brain cells.
A naturally occurring substance of interest is nerve growth factor (NGF). Experiments in
aged rats indicate that specific nerve growth factors can stimulate the growth of new
synaptic connections in the hippocampus and, as a result, restore some memory loss.
Although there could be neuro toxic as well as growth enhancing effects in the use of
NGF, scientists are investigating methods of safely in reducing NGF in to the brain,
possibly through the transplant of genetically engineered cells. Other research is
exploring whether changes of or an imbalance in the metabolism of certain elements like
calcium in brain cells may be part of the process by which the cells degenerate and die in
Alzheimers disease.
B. Chemical Deficiencies: - One of the ways in which brain cells communicate with one
another is through chemicals called neurotransmitters. Studies of Alzheimers disease
brains have uncovered diminished levels of various neurotransmitters that are thought to
influence intellectual functioning and behavior. For example, reduced levels of the
neurotransmitter acetylcholine (ACH) have been found in Alzheimers disease. This
finding has been coupled with observations that drugs whose side effects lower Ach
levels in the brain can cause reversible memory problems. These findings have led to a
number of drug studies employing pharmacologic agents to elevate Ach in patients. The
treatments have included lecithin, choline, physostigmine, deprenyl, tacrine hydrochloride
Alzheimers Disease
(THA), and others, used alone or in different combinations with one another. The results
of these experiments are difficult to interpret. In some of these studies, a few Alzheimers
disease patients seem to show minor improvement may be on certain narrow test
measures-and nor usually on significant activities of daily living which would be more
important to the persons family and physician. Nonetheless the researchers, enthusiasm is
understandable, for they are dealing with the potential modifiability of underlying
physiological phenomena that influence the Alzheimers disease symptoms. The drugs
they are studying now may not be the right ones, but they may point the way to the
discovery of more effective pharmacologic agents.
One drug in particular, THA or tacrine (trade name, cognex), has been studied
extensively. Early studies indicated that THA appeared to have a slightly positive effect
on patient functioning, but assessment by a skilled observer showed no overall
improvement. More recent studies conducted on patients with mild or moderate
Alzheimers using a higher dosage of tacrine than earlier studies, showed a statistically
significant improvement, both in clinical and caregiver evaluations and in quality of life
measurements. These results caused the food and Drug Administration in the fall of 1993
to approve the drug. Tacrine can however have side effects, including elevation of liver
functioning tests. The family of the patient should be aware that the patient must take the
medication 4 times a day, that blood must be drawn weekly during the dose adjustment
phase, and that a third of patients experience significant adverse effects. As in always the
case, but particularly while better drugs are being developed, caregivers and patients will
have to weigh the possible benefits of the available drug against the cost and the potential
problems incurred.
Alzheimers Disease
C. Toxic Chemical Excesses: Although some researchers have found increased levels
of aluminum, mercury, or other metals in the brains of Alzheimers disease victims, others
have not. And while some investigators have hypothesized that aluminum may play a role
in the genesis of Alzheimers disease, most have regarded aluminum as an effect of the
disorder rather than its cause. In other words, instead of aluminums acting to induce
brain tissue changes in Alzheimers disease, it more likely accumulates in response to
such changes. Research continues in an effort to better understand this phenomenon and
to determine whether the aluminum deposits are a cause of a consequence of the disease,
and if the latter whether they contribute further to the impairment already experienced.
2. The Genetic Theory: Genetic aspects of many diseases are confusing for example a disorder can occur more
frequently in certain families than in others, but still nor be genetic. Since family members
living together are exposed to the same environment they would all be at increased risk if an
environmental toxin or infectious agent were the causative factor in a particular disease .
Furthermore, a disorder can be congenital and not heredity that is prenatal problems can
cause developmental defects not brought on by heredity. And illness can be heredity but
remain in a latent state if some other disease factor does not occur to trigger its onset.
Several connections between Alzheimers disease and Downs syndrome led researchers
initially to look for genetic factors in Alzheimers disease on chromosome 21 the
chromosome that is affected in Downs syndrome. At the present time, several genetic
markers have been identified on chromosomes 21 and 14 in that small number of families
where Alzheimers disease has occurred with unusual frequency at relatively early ages. In
families where the disease has tended to develop at later ages, other studies suggest that
Alzheimers Disease
Alzheimers disease unusually frequent in persons who have a particular from of the
apolipoprotein E (Apo E) of the gene, Out of several variants that occur.
Despite these findings, that extent of genetic and heredity involvement in Alzheimers disease
remains unclear. There are a vast number of people affected with this disorder who are not
part of a strong family pattern. Furthermore, the genetic factors associated with the disease
clearly vary for different families. This has led some investigators to postulate that there may
be a number of subtypes Alzheimers disease, with differing risk factors and causes.
3. The Autoimmune Theory: The bodys immune system, which protects against potentially harmful foreign invaders, may
erroneously begin to attack its own tissues, producing antibodies to its own essential cell.
This is called an autoimmune response, and it may take place in the brain. Some speculate
that certain late life changes in aging neurons (the major nerve cells of the brain) might be
triggering an autoimmune response that evokes symptoms of Alzheimers disease in
vulnerable individuals. Curiously, some antibrain antibodies have been identified in the
brains of those with Alzheimers disease. Their significance, though, is not known, especially
since some antibrain antibodies have also been identified in aging brains without Alzheimers
disease. Moreover, even if changes are occurring in brain neurons to trigger an autoimmune
response, what originally induces these brain cell changes is not known.
4. The Slow Virus Theory: Because a slow acting virus has been identified as a cause of some brain disorders that
closely resemble Alzheimers disease (for example, creutzfeldt jakob disease), a slow virus
has been postulated in Alzheimers
disease. Various researchers have suggested that
Alzheimers Disease
suspicious brain tissue changes in Alzheimers disease victims from the brains of those with
Alzheimers disease, and no immune reaction has been found in the brains of Alzheimers
disease, and no immune reaction has been found in the brains of Alzheimers patients,
comparable to that found in patients with other viral dementias. At present, the possibility of
a viral cause of Alzheimers can not be either decisively eliminate or confirmed.
5. The Blood Vessel Theory: Defects in blood vessels supplying blood to the brain have been studied as a possible cause of
Alzheimers disease. Hardening in the brains arteries . also known as cerebroarteriosclerosis.
Proved not to be a cause of Alzheimers disease. Thus, the hyperbaric oxygen chamber
treatment proved ineffective as a therapy for Alzheimers.
Stroke another blood vessel problem that most often occurs later in life, can cause symptoms
like those of Alzheimers disease. But this condition called multi infarct dementia differs
forms Alzheimers disease. More recently, the blood vessel theory has been expanded to
hypothesize potential defects in the blood brain barrier, a protective membrane like
mechanism that guards the brain from foreign bodies or toxic agents circulating in the blood
stream outside the brain.
There have been several reports of a possible association between serious head injures
involving a loss of consciousness and later onset of Alzheimers disease. One theory as to
why this connection might occur has to do with possible breaks in the blood-brain barrier as a
result of these injuries to the brain.
Risk Factors Or Other Reason Which May Aggravate The AD: -
Alzheimers Disease
Alzheimers is a complex disease thats likely caused by a variety of influences. Although all
of these influences may never be known scientists have identified Alzheimers disease. They
include;
1. Age: Alzheimers usually affects people older than 65 but can rarely, affect those younger than 40.
The average at diagnosis is about 80. Less than 5 percent of people between 65 and 74
Alzheimers for people 85 and older, that number jumps to nearly 50 percent.
2. Heredity: Your risk of developing Alzheimers appears to be slightly higher if a first degree relative
parent sister or brother - has the disease. Although the genetic mechanisms of Alzheimers among
families remain largely unexplained researchers have identified a few genetic mutations that
greatly increase risk in some families. Three genetic mutations are known to cause early onset
Alzheimers. In addition one form of the apolipoprotein E (APOE) gene increases your
chance of developing late onset Alzheimers.
3. Sex:
Women are more likely than men are develop the disease, in part because they live longer.
4. Lifestyle:
The same factors that put you at risk of heart disease, such as with blood pressure and high
cholesterol, may also increase the likelihood that youll develop Alzheimers disease. And
Alzheimers Disease
keeping your body fit isnt your only concern youve got to exercise your mind as well. Some
studies have suggested that remaining mentally active throughout your life, especially in your
later years, reduces the risk of Alzheimers disease. Other studies have found an association
between low education and the risk of Alzheimers. These studies have supported the notion
that people might be able to influence their risk of Alzheimers based on their mental activity.
Some researchers theorize that the more you use your brain, the more synapses you create,
which provides a greater reserve as you age. It remain unclear however, whether lower
education and less mental activity create a risk of Alzheimers or if its simply harder to
detect Alzheimers in people who exercise their minds frequently or who have higher
education.
5. Environment: Researchers are studying environmental factors to discover both the possible causes and the
prevention of Alzheimers. For example, some people with Alzheimers have deposits of
aluminum in their brain. But scientists whove studied environmental sources of aluminumeverything from antiperspirants to drinking water- havent found a link between aluminum
exposure and Alzheimers. At this point, theres no irrefutable evidence regarding any
environmental factor increasing a persons risk of Alzheimers.
6. Head Injury: The observation that some ex-boxers eventually develop dementia leads to the question of
whether serious traumatic injury to the head (for example, with a prolonged loss of
consciousness) may be a risk factor for Alzheimers several studies indicated a definite link
between the two, but others found no link.
Alzheimers Disease
7. Hormone Replacement Therapy: The exact role hormone replacement therapy may play in the development of dementia isnt
yet clear. Results from the large scale study called the womens Health initiative Memory
study indicated an increased risk of dementia for women 65 years and older who had taken
hormone replacement therapy. However, previous studies have suggested that estrogen
supplements given after menopause could reduce the risk of dementia. Additionally, the
womens Health Initiative Memory study didnt study the effect of estrogen on the risk of
dementia if given to women younger than 65.
Alzheimers Disease
SIGN AND SYMPTOMS OF ALZHEIMERS DISEASE

Everyone has occasional lapses in memory. Its often quite normal to forgetthe names of
people whom you rarely see. But its not a normal part of aging to forget the names of
familiar people and objects, Alzheimers disease- which is a progressive, degenerative brain
disease- goes beyond simple forgetfulness. It may start with slight memory loss and
confusion, but it eventually leads to irreversible mental impairment that destroys a persons
ability to remember, reason, learn and imagine. Most people with Alzheimers share certain
sighs and symptoms of the disease. These may include:
Increasing and persistent forgetfulness: -
Alzheimers Disease
At its onset, Alzheimers disease is marked by periods of forgetfulness, especially of recent

events or simple directions. But what begins as mild forgetfulness persists and worsens.
People with Alzheimers may repeat things and forger conversations or appointments. They
routinely misplace things, often putting them in illogical locations. They frequently forget
names of family members and everyday objects.
Difficulties with abstract thinking.
People with Alzheimers may initially
have trouble balancing their checkbook a problem that progresses to trouble

recognizing and dealing with numbers.
Difficulty finding the right word.
It may be a challenge for those with
Alzheimers to find the right words to express thoughts or even follow conversations,
Eventually, reading and writing also are affected.
Disorientation. People with Alzheimers may lose a sense of time and dates. They
may find themselves lost in familiar surroundings. Eventually, they may even wander
from home.
Loss of judgment.
Solving everyday problems such as knowing what to do if
food on the stove is burning, becomes increasingly difficult, eventually impossible.

Alzheimers is characterized by greater difficulty in doing things that require
planning, decision making and judgment.
Difficulty performing familiar tasks.
Once- routine tasks that require
sequential steps, such as cooking, become a struggle as the disease progresses.

Eventually, people with advanced Alzheimers may forget how to do even the most
basic things.
Personality changes.
Alzheimers Disease
People with Alzheimers may exhibit mood swings. They
may express distrust in others, show increased stubbornness and withdraw socially.
Early on this may be response to the frustration they feel as they notice uncontrollable
changes in their memory. Depression often coexists with Alzheimers disease.
Restlessness also is a common sigh. As the disease progresses, people with
Alzheimers may become anxious or aggressive and behave inappropriately.
Ten warning Sign of Alzheimers disease: 1. Memory loss that affects job skills
2. Difficulty performing familiar tasks
3. Problems with language
4. Disorientation to time and place
5. Poor or decreased judgment
6. Problems with abstract thinking
7. Misplacing things
8. Changes in mood or behavior
9. Changes in personality
10. Loss of initiative
Typically loved ones notice very gradual not sudden changes in a person with Alzheimers.
As the disease progresses, signs and symptoms become serious and noticeable enough to
cause people with Alzheimers or their family members to seek medical help. Many people
with Alzheimers disease realize that some things is happening to their memory, which is
often frightening.
Alzheimers Disease
The course the disease takes and how rapidly changes occur vary from person to person. The
average survival rate is eight years after being diagnosed with Alzheimers but some people
live as few as three years after diagnoses, while others olive as long as 20 years.
Alzheimers generally progresses from mild to moderate to severe to, finally profound
impairment. People with mild Alzheimers can usually live alone and function fairly well.
Those with moderate Alzheimers may have greater difficulty coping without supervision.
People with advanced Alzheimers generally can no longer care for themselves.
Alzheimers Disease
THE DIAGNOSIS OF ALZHEIMERS DISEASE

There is currently no single test that can tell if a person has Alzheimer disease. The diagnosis
is made through a systematic assessment which eliminates other possible causes. Until the
time when there is a conclusive test, doctors may continue to use the words probable
Alzheimer Disease. However, you should be aware that doctors making this diagnosis are
accurate 80 to 90 per cent of the time.
Alzheimers Disease
Making the diagnosis can take time. The diagnosis can be made in a family doctors office, a
memory clinic or a hospital. The doctor may or may not feel that the person needs to see a
number of health care professionals to help make the diagnosis. These may include a
psychologist, psychiatrist, neurologist, geriatrician, nurse, social, worker or occupational
therapist. They will look for problems with the person memory, reasoning ability, language
and judgment and how these affect day to day function. So diagnosis is made on the
following processes. The process involves.
Medical History: Either the individual and family members or friends will be asked questions regarding the
persons symptoms now and in the past. There will be questions about past illnesses and
about family medical and psychiatric history.
Mental Status Exam: This part of the process tests the persons sense of time and place as well as the ability to
remember express her self and do simple calculations. it may involve exercises such as
recalling words and objects drawing and spelling, and questions such as What year is it.
Physical Exam: To help rule out other causes, a physical exam will be done. The doctor will look for heart,
lung, liver, kidney or thyroid problems that may be causing the symptoms. To evaluate
whether other nervous system disorders are causing the symptoms, the doctor will test muscle
tone and strength, coordination, eye movement, speech and sensation.
Alzheimers Disease
Laboratory Tests: A Number of tests will be done. Detailed blood work will be ordered to help detect problems
such as anemia, diabetes, thyroid problems or infections that might be contributing to the
symptoms.
Other tests such as X-rays and EEGs (electroencephalogram) may be used to determine the
source of the problem. In some centers, scans may be used. \the following may be
recommended, but are not always necessary for a diagnosis: CT (computerized tomography)
scan and MRI (Magnetic resonance imaging) take images of the brain. In these computerized
techniques changes in the brain is evaluated. These evaluation are as following-
1. Plaques and Tangles

Microscopic brain tissue changes have been described in Alzheimers disease. The two
principal changes are senile or neuritic plaques (chemical deposits consisting of degenerating
nerve cells combined with a form of protein called beta amyloid) and neurofibrillary tangles
(malformations within nerve cells). The brains of Alzheimers disease patients of all ages
reveal these findings on autopsy examination. The formation of amyloid plaques and
neurofibrillary tangles are thought to contribute to the degradation of the neurons (nerve
cells) in the brain and the subsequent symptoms of Alzheimers disease.
As research on Alzheimers disease progress, scientists are describing other abnormal
anatomical and chemical changes associated with the disease. These include nerve cell
degeneration in the brains nucleus basalis of Meynert and reduced levels of the
neurotransmitter acetylcholine in the brains of Alzheimers disease victims. But from a
practical standpoint, the classical plaque and tangle changes seen in the brain at autopsy
Alzheimers Disease
typically suffice for a diagnosis of Alzheimers disease. In fact, it is still only through the
study of brain tissue from a person who was thought to have Alzheimers disease that a
definitive diagnosis of the disorder can be made.
2. Brain scans
Computer-Assisted Tomography (CAT scan) changes become more evident as the disease
progresses-- not necessarily early on. Thus a CAT scan performed in the first stages of the
disease cannot in itself be used to make a definitive diagnosis of Alzheimers disease; its
value is in helping to establish whether certain disorders (some reversible) that mimic
Alzheimers disease are present later on, CAT scans often reveal changes characteristic of
Alzheimers disease, namely an atrophied (shruken) brain with widened sulci (tissue
indentations) and enlarged cerebral ventricles (fluid-filled chambers).
Several new types of instrumentation are enabling researchers to learn even more about the
brain. Both positron emission tomography (PET scan) and SPECT (single photon emission
computerized tomography) can map regional cerebral blood flow, metabolic activity, and
distribution of specific receptors, as well as integrity of the blood-brain barrier. These
procedures may reveal abnormalities characteristic of Alzheimers disease. Another method,
magnetic resonance imaging (MRI), probes the brain by examining the interaction of the
magnetic properties of atoms with an external magnetic field. MRI provides both structural
and chemical information and distinguishes moving blood from static brain tissue.
SPECT (single proton emission computed tomography) shows how blood is circulating to the
brain.
PET (positive electron tomography) shows how the different areas of the brain respond
during certain activities such as reading and talking.
Alzheimers Disease
Psychiatric and Psychological Evaluations: A psychiatric evaluation may be helpful in ruling out other illnesses such as depression which
can cause symptoms similar to Alzheimer Disease. Neuro-psychological testing can evaluate
memory, reasoning, writing etc.
Diagnosis by Exclusion
Some scientists think that the results from biochemical research may lead to a diagnostic
marker for certain persons evaluated for Alzheimers disease. For example, research has
discovered a protein called Alzheimers disease Associated protein (ADAP), in the autopsied
brains of Alzheimers patients. The protein, which seems to appear only in people with
Alzheimers is mainly concentrated in the cortex covering the front and side sections of the
brain, regions involved in memory function. Researchers have found ADAP not only in brain
tissue but also in spinal fluid. If they can perfect a test to detect the protein in the
cerebrospinal fluid, or potentially even circulating in the blood. It may be possible to use this
method of diagnosis on living patients.
Many scientists are working at developing other tests or procedures that may someday
identify living persons with the disorder, perhaps even early in its course before behavioral
changes become evident. Still a reliable, specific diagnostic marker for Alzheimers disease is
not yet available.
Meanwhile, Alzheimers disease is the most over diagnosed and misdiagnosed disorder of
mental functioning in older adults. Part of the problem, already alluded to, is that many other
disorders show symptoms that resemble those of Alzheimers disease. The crucial difference,
Alzheimers Disease
though is that many of these disorder unlike Alzheimers disease may be stopped, reversed, or
cured with appropriate treatment. But first they must be identified and not dismissed as
Alzheimers disease or senility.
Conditions that affect the brain and result in intellectual, behavioral, and psychological
dysfunction are referred to as organic mental disorder. These disorders represent a broad
grouping of diseases and include Alzheimers disease. Organic mental disorders that can
cause clinical problems like those of Alzheimers disease, but which might be reversible or
controlled with proper diagnosis and treatment, include the following;
Side Effects of Medications: Unusual reactions to medications, too much or too little
of prescribed medications, combinations of medications which, when taken together,
cause adverse side effects.
Substance Abuse: Abuse of legal and/or illegal drugs, alcohol abuse.
Metabolic Disorders: Thyroid problems, nutritional deficiencies, anemias etc.
Circulatory Disorders: Heart problems, strokes, etc
Neurological Disorders: Normal -pressure hydrocephalus, multiple sclerosis etc.
Infections: Especially viral or fungal infections of the brain.
Trauma: Injuries to the head.
Toxic Factors: Carbon monoxide, methyl alcohol, etc.
Tumors: Any type within the skull--whether originating or metastasizing there.
In addition to organic mental disorders resulting from these diverse causes, other forms of
mental dysfunction or mental health problems can also be confused with Alzheimers disease.
For example, severe forms of depression can cause problems with memory and concentration
that initially may be indistinguishable from early symptoms of Alzheimers disease.
Alzheimers Disease
Sometimes these conditions, referred to as pseudodementia can be reversed. Other

psychiatric problems can similarly masquerade as Alzheimers disease, and like depression,
respond to treatment.
Of course, not all memory changes complaints in later life signal Alzheimers disease or
mental disorder. Many memory changes are only temporary, such as those that occur with
bereavement or any stressful situation that makes it difficult to concentrate. In fact, older
people are often accused or accuse themselves of memory changes which are not really
taking place. If a person in his thirties misplaces keys or a wallet, forgets the name of a
neighbor, or calls one sibling by anothers name, nobody gives it a second thought. But the
same normal forgetfulness for people in their seventies may raise unjustifiable concern. On
the other hand, serious memory difficulties should not be dismissed as an unavoidable part of
normal aging. Since rigorous studies on intelligence in later life show that healthy people
who stay intellectually active maintain a sharp mind throughout the life cycle, noticeable
decline in older adults that interferes with functioning should be clinically explored for an
underlying problem.
PATHOPHYSIOLOGY
Alzheimers Disease
Two microscopic changes occur in the brain in Alzheimers disease: senile plaques develop
between neurons, and neurofibrillary tangles develop within neurons. These changes are
thought to be intricately related to the cause, development, and course of the disease.
Researchers have speculated that inflammation around palques destroys neighboring neurons.
Plaques, which are composed of b-amyloid polypeptides, seem to form as a result of
disorders in processing b-amyloid and its precursor protein. A combination of genetic
predisposition and environmental influences is probably responsible. One of these influences
may be sub clinical ischemia because patients with high blood pressure and elevated
cholesterol levels tend to have an increased risk for Alzheimers disease
Neurofibrillary tangles are made up partly of a protein called tau. Which links together to
form filaments. The density of these filaments within neurons in the brain is directly related
to the severity of dementia. It is unclear why tangles form, but different all alleles of a gene
are known to create forms of tau that are more likely to tangle. It is also unclear whether
tangles are linked to plaque formation. The ultimate effect of the tangles, however, is
compromise of micro tubular functions, with eventual destruction of the neuron.
Alzheimers disease is a progressive illness with symptoms such as memory loss and
impaired thinking that gradually get worse. This is followed by loss of ability to do everyday
things, behavioral difficulties and gradual loss of interaction with what happening so far there
is no cure, and no treatment that will stop the condition developing. However,
drugs can
certain
slow down the progress of the disease and improve a persons thinking and
functioning.
While physical treatment may be limited there is much that can be done for the psychological
health of people with Alzheimers disease and their cares. Seeking early diagnosis and
Alzheimers Disease
receiving information about the condition early in the illness helps patients and cares prepare
for what lies ahead, rather than discover things alone by default. Support groups, specialist
dementia services and talking treatments can be of immense benefit for people learning to
lice with the condition. It is important for cares to get support and to look after their own
physical and mental health.
People with Alzheimers disease may have other problems alongside it, such as psychosis,
depression or a physical illness such as pneumonia. If these are treated effectively, the quality
of life for people with Alzheimers and their cares can be greatly improved. Researchers are
working to find new, more effective ways to treat Alzheimers disease.
Drug Treatments for Cognitive Problems: Cholinergic drugs are the most common drugs for cognitive problems in Alzheimers disease.
They aim to preserve the chemical neurotransmitter acetylcholine (decreased in Alzheimers)
by stopping an enzyme called acetyl cholinesterase, (the enzyme that normally breaks it
down) from working. Three drugs in this category are recommended for mild to moderate
Alzheimers by the National Institute of clinical Excellence (the body responsible for offering
guidance on treatment for the National Health service in the UK):
Donepezil or Aricept - Probably the most widely used medication. People with mild to
moderate Alzheimers disease3 can usually tolerate it; but not all people respond to it. If it
does work it can improve thinking and reduce behavioral problems.
Rivastigmine tartrate, ENA 713 or Exelon- This drug can significantly improve
cognitive function in people with mild to moderate Alzheimers disease and is particularly
useful in the treatment of sufferers with other medical condition for example those with
Alzheimers Disease
vascular risk factors. This is because there seems to be very little interaction with other
common tablets prescribed to the elderly.
Galantamin or Reminyl - has recently gained approval for use in Europe. It has a
slightly different action to the other cholinergic drugs, but whether this makes it more
effective is unclear. The dual action is being studied, but this drug has extensive evidence to
show its effects in all domains of Alzheimers disease, and a significant effect on caregiver
burden as well.
Acetylcholinesterase Inhibitors: The cholinesterase inhibitor tacrine (Cognex) is used rarely because of potential liver toxicity
and the need for frequent laboratory monitoring. The acetyl cholinesterase inhibitors
donepezil (Aricept), rivastigmine (Exelon ), and galantamine (Reminyl) have been proved
effective in clinical trails. Compares the pharmacologic characteristics of the three acetyl
cholinesterase inhibitors and provides dosing and cost information.
While no drug has been shown to completely protect neurons, agents that inhibit the
degradation of acetylcholine within the synapse are the main stay of treatment for
Alzheimers disease. Cholinesterase/ acetylcholinesterase inhibitors are the only agents
approved by the U.S. Food and Drug Administration for the treatment of Alzheimers disease.
Other drugs have been studied, but their use remains controversial.
Table 1
Alzheimers Disease
Acetylcholinesterase Inhibitors Used in the Treatment of

Alzheimers Disease
Drug
Pharmacological
Dosages
Actions
Target
Minimum
Dosages
Therapeutic
Donepezil
Acetylcholinestera
Start at 5 mg
Dosages
10 mg. 5mg. daily
(Aricept)
se inhibitor
once daily,
once
Cost
$ 142
Taken at Bed
time; After 6
Weeks Increase
to 10 mg once
Rivastigmi Ne Acetycholinestera
Daily.
Start at 1.5mg
6mg
(Exelon)
se inhibitor,
twice daily,
twice
Butyrylcholinester
taken with food
daily
Ace inhibitor
; at two week
3 mg twice daily
$ 134
8 mg twice daily
$ 130
intervals,
Increase each
dose by 1.5mg
upto dosage of
Galantamin
(Reminyl )
E Acetylcholinestera
mg twice
Start at 4mg
12mg
se inhibitor
twice daily with twice
Nicotinic receptor
food; at
Action
interval,
daily
Alzheimers Disease
increase each
dose by 4mg
upto a dosages
of mg twice
daily
*-- Manufacturers recommendation on the dosage that produces the best results.
*-- The lowest dosage at which a statistically significant improvement in cognition over
placebo was noted.
*-- Estimated cost to the pharmacist for one month of therapy at the target dosage based on
average wholesale prices (rounded to the nearest dollar) in Red book. Montvale, N.J.:
Medical Economics Data, 2003. Cost to the patient will be higher, depending on prescription
filling fee.
*- This dosage can be used in patients with moderate hepatic or renal disease; galantamine
is not recommended for use patients with severe.
Hepatic or Renal Disease: All three drugs have a low incidence of serious reactions, but they commonly have
cholinergic side effects such as nausea, anorexia, vomiting, and diarrhea. Tolerance to these
side effects often develops. However, if therapy with an acetylcholinesterase inhibitor is
interrupted for mare than several days, the drug should be restarted at the lowest dosage and
retitrated, because of renewed susceptibility to side effects.
Instruments that measure cognition, behavior, and functional ability have shown that
acetylcholinesterase inhibitors are beneficial in patients with Alzheimers disease. While
Alzheimers Disease
these instruments are discussed in greater detail elsewhere, the most commonly used scales
are summarized in table.
Table 2
Scales Used in the Management of Alzheimers Disease
Scale
purpose
Mini-mental Measures
State
Examination
cognition
description
on time
Assesses
5 to 10
orientation
minutes
comments
score
decreases
registration
about 2 to 3
attention, recall
points per
and language on
year in
a 30 point scale
patients with
Alzheimers
disease.
Requires
Minimal
Training to
Administer
Useful in
Clinical
Practice
Alzheimers Disease
Alzheimers
measures
assesses
20 to 45
Score
Disease
cognition
cognitive
minutes
decrease by
Assessment
domains with an
6 to 12 points
Scale,
11-item, 70-
per year in
Cognitive
point scale
patients with
Section
Alzheimers
Disease.
Requires
Significant
Training to
administer
research
Instrument
Global
quantifies assesses
Impressions
an overall cognitive
10 to 30
requires a
minutes
consistent
Perception domains,
and
Of change
behavior, and
systematic
Self care on a
interview at
Scale of 1
each visit
(marked
requires
Improvement)
moderate
To 7 ( very much
training to
Worse) often
administer
Used with
most useful
Caregiver input
Alzheimers Disease
in research
Neuropsychiatri
Measures
Assesses
1 0 to 20
C Inventory
disturbed
severity and
Behaviors
frequency of 12
clinical
Symptoms (e.g.,
practice, it
Agitation,
may be more
minutes
Useful in
research ; in
Irritability,
useful to use
Depression,
a global
Hallucinations);
approach to
Also measures
assess
Caregiver
disturbed.
Physical self-
measures
Assesses six
10
requires
Maintenance
ability to
basic tasks and
minutes
minimal
Scale and
accomplish
eight areas of
training to
Instrumental
basic and
higher
administer;
Activities
instrumenta
functioning on a
useful in
Daily living
I tasks
scale of 1 to 5
clinical
practice
Functional
quantifies
scores
5 to 10
Activities
disability
functional
minutes
Questionnaire
capacity on a
Scale of 1
Easy to
complete
Alzheimers Disease
(Normal) to 7
(severely
Incapacitated)
Although clinical trials have shown that treatment with acetylcholinesterase inhibitors delays
nursing home placement and improves cognition and functional ability. These benefits may
not apply to all patients with Alzheimers disease. For example, patients might be excluded
from a study if they have significant coexisting illnesses with symptoms that could be
confused with drug side effects. Consequently, the study population might consist of patients
who are more likely to respond to the drug.
Nonetheless, it is safe to conclude that patients who tolerate and respond to
acetylcholinesterase inhibitors will experience modest congnitive improvements. In fact,
deterioration of cognition will be delayed by one year in about 20 percent of treated patients
(as measured by a seven -point improvement on the Alzheimers Disease Assessment Scale,
Cognitive Section). Summarizes evidence for the benefits of acetylcholinesterase inhibitors.
Alzheimers Disease
Problems with Cholinergic Drugs:
They May Have Side Effects; such as nausea, diarrhoea and abdominal pain in
some people.
They Do Not Work Forever ; Their effects usually wear off in the short to mid
term. The progress of the disease may be slowed down for several months (especially
in people with mild Alzheimers disease but is not stopped.)
They May Interact with Other Drugs; It is important to check that all drugs
taken (prescription and over the counter) are compatible.
They May inhibit The Release Of Acetylcholine In The Long Run :

Cholinergic drugs work to increase amounts of acetylcholine in the brain. Theres a
danger that the brain will adapt to these increases, and will consequently produce less
acetylcholine. In these cases, an effect could be worsening cognitive problems,
Especially if the drug is stopped too precipitously.
Drug treatments for co-existing conditions

People with Alzheimers disease often experience physical and mental health problems
alongside it, including depression, sleep disturbances, behavioral problems and psychosis.
Once physical causes are eliminated, and if behavioral methods and support do not help these
problems, then drug treatment may be given.
Antipsychotics-preferably atypical, such as risperidone:

These drug may be given to people with Alzheimers disease who are aggressive or agitated.
They are also given for psychotic symptoms such as delusions or paranoia.
Alzheimers Disease
Typical antipsychotics are best not used as there is evidence they worsen the disease and little
evidence that they are that effective. Before any drugs are used, a through assessment is made
of the persons social and environmental situation, and a physical examination carried out to
check they are not in pain. This would usually be carried out by a doctor, in collaboration
with experienced community staff. Any drugs used should e reviewed to ensure they are
having the desired effect, and because these behavioral problems wax and wane in
Alzheimers disease, reviewed again after about four months to ensure they are still needed.
Anticonvulsants such as carbamazepine:

The use of mood stabilizers has increased in recent years, in spite of little published proof of
their benefit. A series of small number trails using both carbamazepine and valproate are
encouraging-but a definitive study has not occurred. It would be appropriate to use these
drugs where agitation or distress was not directly caused by psychotic phenomena (where an
antipsychotic would be a better option), and this seems to be where anecdotal reports claim
they do well, on their own or to supplement other therapies.
Anti-depressants, such as paroxetine, fluoxetine:

Many people with Alzheimers disease experience an episode of depression. This is happens
at any stage of the illness, not just early - and the reason is not fully understood. The only
published study of an antidepressant is using moclobemide. This is a rarely used drug and
most people choose a selective serotonin reuptake inhibitor (paroxetine, fluoxetine) or a
mixed noradrenergic and serotonergic drug (mirtazapine, venlafaxine).
Older drugs, especially tricyclics (amitryptilline, prothiaden) have a high number of side
effects and adverse events in patients with Alzheimers disease. Cognitive problems such as
Alzheimers Disease
memory loss can be a sign of depression as well as Alzheimers and anti-depressants can
improve these problems. But older people can be more susceptible to side-effects of anti
depressants than younger people and care taken accordingly.
Sleeping tablets:
These are often given for night time disturbance, or day/night reversal that is some times
seen. Old valium-like drugs can accumulate in older people and cause confusion. Lorazepam
is metabolized normally, so is safer to use. It is probably better to use newer drugs like
zopiclone, zolpidem or zalepton for sleep induction, or one older antidepressant in common
use is
trazodone, which is quite sleep inducing. Antipsychotics and sedative old tricyclics are often
inappropriate but still frequently used.
Selegiline
A number of studies have examined evidence for the use of selegiline (Eldepryl), a selective
monoamine oxidase inhibitor, in the treatment of Alzheimers disease. Most of these studies
have shown some improvement in cognition, behavior, and mood, but little evidence of a
global benefit in cognition, functional ability, and behavior. In 2000, the authors of a meta
analysis of 15 clinical trials concluded that there was not enough evidence to recomment
selegiline as a treatment for Alzheimers disease. Because of the risk of stupor, rigidity,
severe agitation, and elevated temperature, selegiline therapy is contraindicated in patients
who are taking meperidine (Demerl), and this precaution often is extended to other opioids.
Concurrent use of selegiline with tricyclic antidepressants and selective serotonin reupatake
Alzheimers Disease
inhibitors also should be avoided. These restrictions may limit the use of selegiline in patients
with Alzheimers disease.
Estrogen
Several descriptive studies have shown that postmenopausal women who take estrogen have
a lower incidence of Alzheimers disease. In addition, a recent review of estrogen and
neuroimaging studies demonstrated improved cerebral metabolism in women taking
estrogen. Although estrogen may have a neuroprotettive effect, it does not appear to improve
cognition or function in patients with Alzheimers disease, and the combination of estrogen
and progestin actually may increase the risk for dementia and stroke.
Anti-Inflammatory Drugs
Inflammation surrounding b-amyloid plaques with resultant destruction of neurons is thought
to be a key factor in the pathogenesis of Alzheimers disease. Observational studies have
found that persons who regularly use nonsteroidal anti-inflammatory drugs (NSAIDS) have a
decreased incidence of Alzheimers disease. Thus, NSAIDS likely have some neruoprotective
effect. However, several studies of anti-inflammatory drugs d not show a benefit for
treatment. COX-2 inhibitors are a new class of anti-inflammatory medications that function
like NSAIDS, but are protective of the stomach and far less likely to cause bleeding. One
clinical trial that looked at the use of COX-2 inhibitors in slowing Alzheimers disease
symptoms found no benefit. This might be due to the fact that COX-2, the enzyme inhibited
by these drugs, is itself protective of brain cells, and inhibiting it may remove the protection.
Talking therapies and support
Alzheimers Disease
Emotional and practical support, understanding and advice is essential to both the person with
Alzheimers and their care (s). People respond to their condition in very different ways and so
treatment should be geared to the individual.
Talking therapies such as counselling can help people cope with the demands of
caring for someone with the demands of caring for someone with Alzheimers disease.
It can also help people with Alzheimers especially in the early stages of the disease.
Specialist dementia services and groups can improve the quality of life of sufferers
and cares by providing information. Support, understanding and respite care (link to
Alzheimers Disease Society). Groups and services helpful for people with dementia
may include:
Reminisence therapy encourages people to talk about past events often assisted by photos,
music, object and videos of the past. There has been very little research in this area but it can
temporarily improve the mood and cognitive kills of people with Alzheimers .
Creative therapies such as music, dance, crafts, art and gardening are stimulating and can
help people express themselves and make sense of their environment.
Behavior therapies usually offered by psychologists working in the memory assessment
services, but also from occupational therapy and occasionally physiotherapy services.
Behavioral therapies may be useful in offering guidance on dealing with (and preventing)
difficult behaviors. Find out more from Alzheimers Society leaflet.
Cares themselves constantly come up with ingenious solutions t everyday Problems, hence
the value of meeting in cares groups. Some people respond to dementia by becoming angry
and argumentative, whereas other people will be passive and depressed. Most people are
affected by their environment. Simple behavioral techniques can identify contributing factors
Alzheimers Disease
that may help to stop problem behavior or allow the care to cope with it. S study of care
training in New York showed a delay in the suffer going into a nursing home of almost a year,
when the care was better able to understand what was happening.
Acupuncture Appears to Improve Mood and Cognitive FunctionsAlzheimers disease affects women more frequently than men, and it is characterized by
shrinkage of the frontal or temporal lobes and nerve cell death in several areas of the brain,
leading to a loss of key mental functions such as memory, learning and concentration.
Several therapies have been employed to slow down or reverse the effects of Alzheimers
disease, ranging from an increased intake of vitamins and antioxidants to using nicotine
patches to a new class of drugs called cholinesterase inhibitors. Patches and large doses of
vitamins may have unwanted side effects, however and the long term benefits of
cholinesterase inhibitors remain largely unknown.
New research presented at the recent World Alzheimers conference in Washington, D.C. has
shown promising results with another from of Treatment : acupuncture. In two separate
studies- one at the Wellesley college Center for Research on Women, the other at the
University of Hong Kong scientists have found that acupuncture can increase a patients
verbal and motor skills and improve mood and cognitive function.
In the first study, Dr. Nancy Emerson Lombardo and team of colleagues at Wellesley College
in Massachuestts studied 11 patients, 10 with Alzheimers and one with vascular dementia.
Subjects were treated with acupuncture twice a week for three months, with each subject
receiving a minimum of 22 treatments. Patients were subjected to a variety of tests before and
after being treated, including the Cornell Scale for Depression, the Speilberger State Anxiety
Inventory, and the Mini-Mental Status Exam (MMSE) for cognitive function.
Alzheimers Disease
The researchers found statistically significant improvements in the depression and anxiety
scores of patients. For example, the average Spieberger anxiety score at the start of treatment
was 49.5 at the end of three months, it had decreased to 40.1 four subjects experienced
substantial improvement in mood symptoms after undergoing acupuncture; of those whose
moods improved, two also showed improved MMSE scores, and third improved in tests for
fluency and naming ability.
While cognitive function was not measured scientifically (no control group was used),
Lombardo said that those delivering treatment seemed to note an improvements, in their
subjects thinking skills along with the other improvements, which she believes indicates a
close relationship between cognitive ability, anxiety and depression.
In Dr. Kaos study, eight patients diagnosed with mild to moderate Alzheimers disease were
treated at the University of Hong Kong. Treatment consisted of needling and fine finger
turning at eight acupoints: the si shen cong (Estra 7, four points on the scalp), shen men (HT
7 on the wrists) and Tai Xi (K13 on feet). Needles were inserted 0.5 inches at an angle in to si
shen cong 0.5 inches directly in shem men: and 0.8 inches directly in to tai xi.
Needling for each acupoint lasted a total of 30 minutes, comprising the needle testing and its
reinsertion after every 10 minutes of therapy; patients received a seven day treatment cycle
with a three-day break in between for a total of 30 days.
Patients were graded using the TCM Symptoms Checklist for Alzheimers and the MMSE
exam to measure their levels of orientation; memory; attention; and the ability to name on
object, follow verbal and written commands, and write a sentence spontaneously.
After being treated Kaos team reported that patients significantly improved on measures of
verbal orientation and motor coordination and had higher overall MMSE scores. They also
Alzheimers Disease
noted that patients showed a significant overall clinical improvement on the TCM
checklist, leading the researchers to conclude that acupuncture treatment has shown
significant therapeutic effects in reducing the symptoms of Alzheimers disease.
Nevertheless, these studies represent an important step forward in the research of both
acupuncture and Alzheimers disease. Because they showed such promising results, the work
by Kao and Lmbardo could help lay the groundwork for larger, controlled investigations to
determine how acupuncture combats Alzheimer s which could eventually lead to safer,
inexpensive forms of care for the more that four million Americans who currently suffer from
the disease.
Alzheimers Disease
REFERENCES
Alzheimers Disease
1. Alzheimers Association. Caregiver stress: signs to watch for steps to take. Chicago:
Alzheimers Association: 1995 Accessed April 2003
2. Arai, H., Ichimiya, Y., Kosaka, K, Moroji, T. and Iizuka, R (1992), neurotransmitter
changes
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Psychopharmacol. And Biol. Psychiat. 16, 883-890.

3. Beal MF. Aging, energy, and oxidative stress in neurodegenerative diseases. Annals of
Neurology 1995;38(3): 357-66.
4. Berrios G E and Freeman H (1991) Alzheimer and the Dementias. London , Royal
Society of Medicine.
5. Berrios G E (1989) Non cognitive symptoms and the diagnosis of dementia.
Historical and clinical aspects. British journal of psychiatry 154:11-16.
6. Berrios G E (1990) Alzheimers disease: a conceptual history. International Journal of
Geriatric Psychiatry 5:355-365.
7. Breitner, J.C.S., Welsh, K.A., Helms, M.J., Gaskell, P.C., GAu, B.A., Roses,A.D.,
pericak Vance, M.A., Saundrs, A.M. (1995) Delayed onset of Alzheimers disease
with nonsteroidal anti-inflammatory and histamineH2blocking drugs. Neruobiol .
Aging 16:523-530.
8. Emerson Lombardo N, et al. Acupuncture to treat anxiety and depression in
Alzheimers disease and vascular dementia: a pilot feasibility and effectiveness trial.
Presented at the World Alzheimers Conference. Washington, D.C., July 9-18,2000.
9. Good man, Y., Mastton, M.P. (1994) Secreted forms of a amyloid precursor protein
protect hippocampal neurons against amloid a peptide induced oxidative injury. Exp.
Neurol 128:1-12.
10. Greenson, H., Jarvik, L. (1987) translation of Alzheimer, A. (1907) About a peculiar
disease of the cerebral cortex. Alzheimers Disease and Associated Disorders 1:7-8.
Alzheimers Disease
11. Harrison, P.J. (1986) pathogenesis of Alzheimers disease beyond the cholinergic
hypothesis discussion aper. Journal of the Royal Society of Medicine 79:347-352.
12. HARVEY, JOHNS, OWENS, ROSS, The Principle and practice of medicine, 16101615
13. Kao H et al. Acupuncture enhancement in clinical symptoms and cognitive motor
abilities of the Alzheimers disease patients. Presented at the World Alzheimers
Conference, washington, D.C., July 9-18-2000.
14. Lowton MP, Brody EM. Assessment of older people : self maintaining and
instrumental activities of daily living. Gerontologist 1969;9: 179-86.
15. Maurer K, Yolk S, Gerbaldo H (1997) Auguste D alzheimers disease. Lancet
349:1546-1549.
16. NICE issues guidance on drugs for Alzheimers disease. National institute for clinical
excellence Accessed April 2003.
17. Sano M Ernesto C, Thomas RG, et al. A controlled trialof Slegiline, alpha
tocopherol, or both as treatment for Alzheimer,s disease. N Engl J Med 1997; 336
1216- 1222.
18. Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Rerris SH, et al.
Diagnosis and treatment of Alzheimer disease and related disorders. Consensus
statement of the American Association.
19. The MIT press. German, D.C. White, C.L. and Sparkman D.R. (1987).Alzheimers
disease: Neurofibrillary tangles in juclei that project to the cerebral cortex.
Neuroscience 21(2), 305-312.
20. www.alzheimer.org.uk.
21. www.nice.org.uk/article.asp?a=14406.
22. www.alz.org/ResourceCenter/factsheets/Brochure-%20careguverstress.pdf.
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B.

Pharma Part IV, (2008)

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Maharishi Arvind Institute Of Pharmacy, Jaipur

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Cross Section Area of Brain Which Affects In AD: -

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Maharishi Arvind Institute Of Pharmacy, Jaipur

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Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Amyloid Plaques: One of the hallmarks of Alzheimers disease is the accumulation of

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Plaques: Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

B. Pharma Part IV, (2008)

B. Pharma Part IV, (2008)

A. Biochemical changes in growth (Trophic) factors: -Much research is taking

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

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disease. Various researchers have suggested that

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Risk Factors Or Other Reason Which May Aggravate The AD: -

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

SIGN AND SYMPTOMS OF ALZHEIMERS DISEASE

Increasing and persistent forgetfulness: -

Maharishi Arvind Institute Of Pharmacy, Jaipur

B. Pharma Part IV, (2008)

At its onset, Alzheimers disease is marked by periods of forgetfulness, especially of recent

Difficulties with abstract thinking.

People with Alzheimers may initially

have trouble balancing their checkbook a problem that progresses to trouble

Difficulty finding the right word.

It may be a challenge for those with

Solving everyday problems such as knowing what to do if

food on the stove is burning, becomes increasingly difficult, eventually impossible.

Difficulty performing familiar tasks.