p conversations and events. Repeated questions, some problems

p { margin-bottom: 0.25cm; line-height: 120%; }a:link { }

Alzheimer’s
disease (AD), also known as Senile Dementia of the Alzheimer
Type (SDAT) or simply Alzheimer’s is the most common form of
dementia. This incurable, degenerative, terminal disease was first
described by a German psychiatrist and neuropathologist Alois
Alzheimer in 1906 and was named after him.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Alzheimer’s
disease (AD) is a slowly progressive disease of the brain that is
characterized by impairment of memory and eventually by disturbances
in reasoning, planning, language, and perception.

Many
scientists believe that Alzheimer’s disease results from an increase
in the production or accumulation of a specific protein (beta-amyloid
protein) in the brain that leads to nerve cell death.Generally,
it is diagnosed in people over 65 years of age, although
the less- prevalent early onset of Alzheimer’s can occur much
earlier.

In
2006, there were 26.6 million sufferers worldwide.

Alzheimer’s
is predicted to affect 1 in 85 people globally by 2050.

1)
Early Stage

STAGES:

1)
Early Stage

This
is considered as a mild/early stage and the duration period is 2-4
years.

Frequent
recent memory loss, particularly of recent conversations and events.

Repeated
questions, some problems expressing and understanding language.

Writing
and using objects become difficult and depression and apathy can
occur.

Drastic
personality changes may accompany functional decline.

Need
reminders for daily activities and difficulties with sequencing
impact driving early in this stage.

2)
Second stage

This
is considered as a middle/moderate stage and the duration is 2-10
years.

Can
no longer cover up problems. 

Pervasive
and persistent memory loss impacts life across settings.

Rambling
speech, unusual reasoning, confusion about current events, time, and
place. 

Potential
to become lost in familiar settings, sleep disturbances, and mood or
behavioral symptoms accelerate.

Nearly
80% of patients exhibit emotional and behavioral problems which are
aggravated by stress and change.

Slowness,
rigidity, tremors, and gait problems impact mobility and
coordination. 

Need
structure, reminders, and assistance with activities of daily living.

3)
Moderate stage

Increased
memory loss and confusion.

Problems
recognizing family and friends.

Inability
to learn new things.

Difficulty
carrying out tasks that involve multiple steps (such as getting
dressed).

Problems
coping with new situations.

Delusions
and paranoia.

Impulsive
behavior.

In
moderate AD, damage occurs in areas of the brain that control
language, reasoning, sensory processing, and conscious thought

4)
Last stage

This
is considered as the severe stage and the duration is 1-3 years.

Confused
about past and present. Loss of recognition of familiar people and
places

Generally
incapacitated with severe to total loss of verbal skills.

Unable
to care for self.  Falls possible and immobility likely.

Problems
with swallowing, incontinence, and illness.

Extreme
problems with mood, behavioral problems, hallucinations, and
delirium.

Patients
need total support and care, and often die from infections or
pneumonia

SYMPTOMS
:

CAUSE
AND RISK FACTORS

Scientists
don’t yet fully understand what causes AD, but it is clear that it
develops because of a complex series of events that take place in the
brain over a long period of time. It is likely that the causes
include genetic, environmental, and lifestyle factors.

Some
drug therapies propose that AD is caused by reduced synthesis of the
neurotransmitter acetylcholine.

Other
cholinergic effects have also been proposed, for example, initiation
of large-scale aggregation of amyloid leading to generalized
neuroinflammation.

Alzheimer’s
disease is characterized by a build-up of proteins in the brain.
Though this cannot be measured in a living person, extensive autopsy
studies have revealed this phenomenon. The build-up manifests in two
ways:

Plaques–
deposits of the protein beta-amyloid that accumulate in the
spaces between nerve cells

Tangles
– deposits of the protein tau that accumulate inside of
nerve cells

The
signature findings are intracellular neurofibrillary tangles (NFTs),
extracellular
neuritic plaques, degeneration of neurons and synapses, and
cortical
atrophy.
• Mechanisms
proposed for these changes are:
? ?-Amyloid
protein aggregation, leading to formation of plaques
?
Hyperphosphorylation
of tau protein, leading to intracellular NFT
development
and collapse of microtubules
? Inflammatory
processes—levels of multiple cytokines and chemokines
are
elevated in AD brains
?Neurovasculature
dysfunction
?Oxidative
stress
?Mitochondrial
dysfunction
• Neuritic
plaques are lesions found in brain and cerebral vasculature.
• Whether
genetic variations promote a primary

?
-amyloidosis in the
majority
of AD patients is unresolved.
• Density
of NFTs correlates with severity of dementia.
• While
there is a variety of neurotransmitter deficits, loss of cholinergic
activity
is most prominent and correlates with AD severity.
• It
is clear that replacement of acetylcholine activity cannot compensate
for
all
the changes that take place in AD.
• Deficits
that exist in other pathways are:
?Serotonergic
neurons of the raphe nuclei and noradrenergic cells of the
locus
ceruleus are lost
?Monoamine
oxidase type B activity is increased
?Glutamate
pathways of the cortex and limbic structures are abnormal
• Excitatory
neurotransmitters, including glutamate, have been implicated
as
potential neurotoxins in AD.
• Risk
factors for AD are hypertension, elevated low-density lipoprotein
cholesterol,
low high-density lipoprotein cholesterol, and diabetes.

Diagnosis

Alzheimer’s
disease is usually diagnosed clinically from the patient
history, collateral history from relatives, and clinical
observations, based on the presence of characteristic neurological
and neuropsychological features and the absence of alternative
conditions.

Advanced
medical imaging with computed tomography (CT) or magnetic resonance
imaging (MRI), and with single photon emission computer tomography
(SPECT) or positron emission tomography (PET) can be used to help
exclude other cerebral pathology or subtypes of dementia.

The
diagnosis can be confirmed with very high accuracy post-mortem when
brain material is available and can be examined histologically.

PET
scan of the brain of a person with AD showing a loss of function in
the temporal lobe.

Diagnostic
Tools:

Neuropsychological
tests such as the mini-mental state examination (MMSE) are widely
used to evaluate the cognitive impairments needed for diagnosis. More
comprehensive test arrays are necessary for high reliability of
results, particularly in the earliest stages of the disease.

Psychological
tests for depression are employed, since depression can either be
concurrent with AD, an early sign of cognitive impairment, or even
the cause.

When
available as a diagnostic tool, SPECT and PET neuroimaging are used
to confirm a diagnosis of Alzheimer’s in conjunction with evaluations
involving mental status examination. In a person already having
dementia, SPECT appears to be superior in differentiating Alzheimer’s
disease from other possible causes, compared with the usual attempts
employing mental testing and medical history analysis.

Microscopy
image of a neurofibrillary tangle, conformed by hyperphosphorylated
tau protein

PHARMACOTHERAPY
OF COGNITIVE SYMPTOMS
Managing
blood pressure, cholesterol, and blood sugar may reduce the risk
of
developing AD and may prevent the worsening of dementia in patients
with
AD.
• Current
pharmacotherapeutic interventions are primarily symptomatic
attempts
to improve or maintain cognition. Table 67-3 may be used as an
algorithm
for managing cognitive symptoms in AD.
• Successful
treatment re

CHOLINESTERASE
INHIBITORS

No
direct comparative trials have assessed the effectiveness of one
agent
over
another.

Donepezil,
rivastigmine, and galantamineare indicated in mild to moderate AD,
while donepezil is also indicated in severe AD.
• If
the decline in MMSE score is more than 2 to 4 points after treatment
for
1
year with the initial agent, it is reasonable to change to a
different
cholinesterase
inhibitor. Otherwise, treatment should be continued with
the
initial medication throughout the course of the illness.
• The
most frequent adverse effects are mild to moderate GI symptoms
(nausea,
vomiting, and diarrhea), urinary incontinence, dizziness, head-
ache,
syncope, bradycardia, muscle weakness, salivation, and sweating.
Abrupt
discontinuation can cause worsening of cognition and behavior in
some
patients

Donepezil
(Aricept) is a piperidine derivative with specificity for inhibi-
tion
of acetylcholinesterase rather than butyrylcholinesterase.

Rivastigmine
has central activity at acetylcholinesterase and butyrylcho-
linesterase
sites, but low activity at these sites in the periphery.

Galantamine
is a cholinesterase inhibitor that also has activity as a
nicotinic
receptor agonist.

Tacrine
was
the first cholinesterase inhibitor approved for the treatment
of
AD, but it has been replaced by safer drugs which are better
tolerated.

Memantine
(Namenda) blocks glutamatergic neurotransmission by antago-
nizing
N -methyl- D aspartate receptors, which may prevent excitotoxic
reac-
tions.
It is used as monotherapy, and data suggest that when it is combined
with
a cholinesterase inhibitor, there is improvement in cognition and
activities
of daily living.
? It
is indicated for treatment of moderate to severe AD.
? It
is not metabolized by the liver, but is primarily excreted unchanged
in
the
urine (half-life of elimination = 60 to 80 hours).
? It
is usually well tolerated, and side effects include constipation,
confu-
sion,
dizziness, hallucinations, headache, cough, and hypertension.
? It
is initiated at 5 mg/day and increased weekly by 5 mg/day to the
effective
dose of 10 mg twice daily. Dosing must be adjusted in patients
with
renal impairment.
• Recent
trials do not support the use of estrogen to prevent or treat
cognitive decline.
• Evidence
related to the role of vitamin E in preventing AD is mixed, and
conclusions
cannot be drawn at this time.

Because
of a significant incidence of side effects and a lack of compelling
evidence,
Nonsteroidal antiinflammatory drugs are not recommended
for
treatment or prevention of AD.

There
is interest in the use of lipid-lowering agents, especially the 3-
hydroxy-3-methylglutaryl
coenzyme A–reductase inhibitors, to prevent
AD.
Pravastatin and lovastatin, but not simvastatin , were associated
with
a
lower prevalence of AD. Further study is needed before these agents
can
be
recommended for this use.
• A
metaanalysis indicated that EGb 761 (an extract of ginkgo biloba)
may
have
some therapeutic effect at doses of 120 to 240 mg of the standard
leaf
extract
twice daily. Because of limited efficacy data, the potential for
adverse
effects
(e.g., nausea, vomiting, diarrhea, headache, dizziness, weakness, and
hemorrhage),
and the poor standardization of herbal products, it is recom-
mended
that ginkgo biloba be used only with caution.
?Ginkgo
biloba should not be used in individuals taking anticoagulants
or
antiplatelet drugs, and should be use cautiously in those taking
nonsteroidal
antiinflammatory drugs

• Although
initial studies suggest potential effectiveness of huperzine A, it
has not been adequately evaluated for treatment of AD.

PHARMACOTHERRAPY
OF NON COGNITIVE SYMPTOMS:

Pharmacotherapy
is aimed at treating psychotic symptoms, inappropriate
or
disruptive behavior, and depression. Medications and recommended
doses
for noncognitive symptoms are shown in Table 67-5.
• General
guidelines are as follows: (1) use reduced doses, (2) monitor
closely,
(3) titrate dosage slowly, (4) document carefully, and (5) periodi-
cally
attempt to reduce medication in minimally symptomatic patients.
• Psychotropic
medications with anticholinergic effects should be avoided
because
they may worsen cognition.
Cholinesterase
Inhibitors and Memantine
Cholinesterase
inhibitors and memantine are first-line therapy in early management
of behavioral symptoms. Modest improvement may be
achieved.
Antipsychotics
• Antipsychotic
medications have traditionally been used to treat disruptive
behaviors
and psychosis in AD patients.
• A
metaanalysis showed that 17% to 18% of dementia patients showed a
modest
treatment response to atypical antipsychotics. Adverse events
included
somnolence, extrapyramidal symptoms, abnormal gait, worsen-
ing
cognition, cerebrovascular events, and increased risk of death.
• Typical
antipsychotics may also be associated with a small increased risk of
death,
as well as more severe extrapyramidal effects and hypotension.
Antidepressants
• Depression
and dementia have many symptoms in common, and the
diagnosis
of depression can be difficult, especially later in the course of AD.
Treatment
with a selective serotonin reuptake inhibitor is usually initiated
in
depressed patients with AD.

Paroxetine
causes more anticholinergic side effects than the other selective
serotonin reuptake inhibitors
.
Venlafaxine may also be used.
• Although
probably equally effective, the tricyclic antidepressants are
usually avoided because of anticholinergic side effects.
Miscellaneous
Therapies
• Carbamazepine
,
mean dose 300 mg/day, may improve psychosis and
behavioral
disturbance in AD patients.
• Oxazepam
and
other benzodiazepines have been used to treat anxiety,
agitation,
and aggression, but they generally show inferior efficacy com-
pared
with antipsychotics. They can also worsen cognition, cause disinhi-
bition,
and increase the risk of falls

PREVENTION:

Baseline
assessment should define therapeutic goals and document cogni-
tive
status, physical status, functional performance, mood, thought pro-
cesses,
and behavior. Both the patient and caregiver should be interviewed.
• Because
target symptoms of psychiatric disorders may respond differently
in
demented patients, a detailed list of symptoms to be treated should
be
documented
to aid in monitoring.
• Objective
assessments, such as the MMSE for cognition and the Functional
Activities
Questionnaire for activities of daily living, should be used to
quantify
changes in symptoms and functioning.
• The
patient should be observed carefully for potential side effects of
drug
therapy.
The specific side effects to be monitored and the method and
frequency
of monitoring should be documented.
• Assessments
for drug effectiveness, side effects, compliance, need for
dosage
adjustment, or change in treatment should occur at least monthly.
• A
treatment period of 6 months to 1 year may be required to determine
whether
therapy is beneficial

x

Hi!
I'm Isaac!

Would you like to get a custom essay? How about receiving a customized one?

Check it out