Transcript Alzheimer’s Disease

By: Carla Alexander, 4th Year Pharmacy Student
March 17th, 2011
 Definition
 Prognosis
 Pathophysiology
 Symptoms
 Treatment
 Functional
Tests
 Exceptional Drug Status
 Dementias:
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Alzheimer’s Disease
Vascular Dementia
Mixed Type Dementia
Frontal Lobe Dementia
Dementia with Lewy Bodies
 Most
common form of dementia is
Alzheimer's Disease (50-75%)
 An
acquired impairment in intellectual
function, involving at least three of the
following:
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Memory
Emotion
Language
Eye-hand skills
Executive function (planning or completing
activities
 Impairment
of cognitive function is sufficient
to interfere with normal daily activities.
 Chronic
 Progressive
neurodegenerative disorder
 No cure to halt progression
 Rate of failure is variable for each person
 Prognosis:

Lasts 3-20years (4.5 yrs avg.)
 Body
is weakened by inactivity, muscle
wasting and decreased immune function

Death usually due to secondary infection, such as
pneumonia
 Significant
impact on society economically.
 Today, half a million Canadians have
Alzheimer's disease or a related dementia.
 1 in 11 Canadians over the age of 65
currently has Alzheimer's disease or a related
dementia.
 One Canadian every five minutes will develop
dementia this year. By 2038, this will become
one person every two minutes
 If nothing changes, the number of people
living with Alzheimer's disease or a related
dementia is expected to more than double
Not a normal part of aging
 Acetylcholine (Ach) is crucial for nerve to nerve
communication
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Depleted in Alzheimer’s Disease
Protein plaques (amyloid, A-Beta) &
neurofibrillary tangles (tau)
Normally present in brain
 Over production and accumulation in Alzheimer’s
Disease
 Toxic to nerve cells
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Nerve cells die and their connections with other
nerve cells are lost; brain cells continue to die
over time
 Damage starts 10+ years before symptoms
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Nerve cell damage
due to amyloid
beta protein and
tau protein.
Decreased ability
to transmit signals
in brain.
Decreased
concentration of
Ach, used for
nerve
communication.
Loss of
activity and
physical
structure of
brain.
 Three
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interrelated aspects:
Memory
Perception
Thought
 As
the disease progresses, a person will
experience new symptoms and an increase in
the severity of older symptoms
 Loss of memory affects perception of events
which affects thinking; thoughts not
remembered, which then affects your
behaviour
Classic Signs/Symptoms of
Alzheimer’s Disease
Wandering, sundowning,
sleep problems
Problems with abstract
thinking
Difficulty performing
familiar tasks
Changes in personalitysocial withdrawal,
inhibition
Problems with language
Loss of initiative
Disorientation to
time/place
Changes in mood &
behaviour- aggression,
agitation, delusions
Poor/decreased judgement
Increased dependency
Misplacing things, easily
distracted
Balance and movement
disorders
90% of patients have behavioural and
psychological symptoms
 Currently, once an ability is lost, it won’t return.
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 No
known, single cause of Alzheimer's
disease.
 However:
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Inherited (Genes – APOEe4)
Head injuries
More frequent in women
 True
diagnosis can only be found post
mortem
 Rule
out treatable causes
 Physical exam
 Cognitive tests (MMSE, clock drawing, FAQ)
 History
 Nurse observations
 Blood work
 Brain Imaging (MRI, CT)- to detect shape and
volume of brain regions

Rule out if pain is underlying problem
As seniors age they become still, sore and hurt
 People with dementia can’t express themselves very
well which triggers agitation
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Depression (Pseudo-dementia)
 Delirium (drugs, infections-UTI causes delirium)
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first check urine
Hypothyroidism
 Vit. B12 deficiency
 Alcoholism
 Drugs & polypharmacy
 Hard of hearing
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 Cognitive
impairment assessed using MiniMental State Examination (MMSE)
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Orientation, learning, naming, drawing,
judgment skills, clock drawing
 Functional
disability is measured with
Functional Assessment Staging Tool (FAST), or
Functional Activities Questionnaire (FAQ)
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FAQ is required by SK drug plan
Rates 10 routine activities from normal (0) to
dependent (3)
Lower the score, the better
Impairment
MMSE Scoring
Mild
25-14
Moderate
13-1 (most behavioural
issues)
Severe
0 (end stage)
Max score: 30 points
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Mild
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has trouble with recent memory
have difficulty with certain complex functions such as
using the telephone, or managing finances, taking
medications or driving
During the mild stage, many people have difficulty
controlling their emotions, and so can become irritable
and short-tempered.
Moderate
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no longer can do complex activities
care for themselves with prompting.
have difficulty learning anything new, they mix up
details
begin to move slowly
Suspiciousness, judgment for personal safety is too
impaired for them to be counted on.
 Severe
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need more and more help with personal care
no longer can control their bowels or bladder
lose weight, and often even lose a sense of who
they are
cannot speak in full sentences
delusional, a common delusion is that people are
stealing from them; another is that where they
live is no longer their house, and they will want
to 'go home'. They can mistake their spouse for
their mother, or a child for a spouse.
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Often sufficient to make a noticeable improvement in
the target symptoms
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Distraction
Avoid confrontation, clear and respectful communication
Safe, familiar environment without hazards (prevent
falls)
Label items
No diet restrictions; snacks help
Exercise/activity (to avoid muscle wasting)
Soothing music
Sundowning – keep active in day; avoid caffeine
AVOID MAJOR SURGERY & Meds if possible
Reserve drug treatment for situations where nonpharmacological interventions have failed or in
situations with dangerous risk,(agitation, hitting).
2 classes of pharmacological agents:
1. Primary meds which attempt to slow the progression
 Cholinesterase inhibitors
 Memantine
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2. Symptomatic meds to manage secondary
complications (depend on stage of progression)
 Antipsychotics
 Antidepressants
 Benzodiazepines
 Hypnotics
 Anxiolytics
 Mood Stabilizers
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Reevaluate all drug therapies q3- 6 mons to see if
still indicated
 Donepezil-Aricept™
 Rivastigmine-
Exelon™ and Exelon ™Patch
 Galantamine-Reminyl ER
 Work
by increasing amount of Ach in the
brain to help messages communicate from
cell to cell.
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Might slow the decline rate – 3-4% over 6 months
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Benefits are small, disease stabilization
No effect on agitation
Trial prescription for ~3months for effect
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If don’t respond to one, may help to switch to
another
Higher doses have better outcomes
 Only work for about 2-3 yrs, then disease
progression too much to have benefit
 Side-effects
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GI issues!, n/v, fatigue, anorexia, decreased heart
rate, insomnia,
Expensive ($172-230/month)
 EDS coverage
 Does not delay institutionalization
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 Works
by blocking glutamate, which at high
doses is toxic to cells, therefore stopping cell
death.
 Small to moderately beneficial effect on
cognition, ADL and behaviour
 Improvements same as cholinesterase
inhibitors (modest)
 Future:
Combining memantine and
cholinesterase inhibitors seems to improve
outcomes. Expensive!
 Memantine is not on SK formulary
 Treats
the behavioural & psychological
component
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Hyperactivity = irritable, restless, disinhibition
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Mood & apathy = anxiety, depressed, no appetite
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Psychosis = delusions, hallucinations, anxiety
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2nd generation antipsychotics:
risperidone (Risperdal)
 olanzapine (Zyprexa)
 quetiapine (Seroquel)
 aripiprazole (Abilify)
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Note: no antipsychotics are approved for
dementia
 Haloperidol (1st generation antipsychotic) not
recommended due to side effects (parkinsonism,
rigidity etc)
 Start low, go slow, keep dose as low as possible
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May improve aggression, insomnia, depression and
psychosis
 Start
with SSRI (citalopram, sertraline)
 Second line venlafaxine
 Avoid TCA’s (amitriptyline) due to
anticholinergic side effects (confusion, and
worsening of Alzheimer’s disease)
 Trazodone
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Sedating side effect, good for insomnia
Also used to treat sundowning
 START
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LOW, GO SLOW, BUT GO!
Reach adequate dose to relieve symptoms of
depression
 Trial
for 6 weeks, longer to take effect in
elderly with dementia
 Early improvement indicators: improvement
in sleep, appetite and energy, before an
improvement in mood
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BZD caution!
Side effects: over sedation, ataxia, altered
sleep, falls motor and cognitive impairment
Indicated for agitations, and anxiety especially
when other agents fail
 Use low doses of short acting agent without
active metabolites (lorazepam, oxazepam,
temazepam)
 Start low, go slow
 Not recommended in elderly—last resort
 Anxiolytics—buspirone
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 Sedating
antidepressant may be
helpful(Trazodone)
 Only use hypnotics when absolutely
required.
 Good alternative is zopiclone vs BZD
 Mood
stabilizers
 Used in agitation, aggression, hostility, sleep
wake disturbance, mania
 Divalproex 125-750mg daily- fewer side
effects
 Carbamazepine 100-600mg daily
 Betablocker—Propranolol 10-80mg/day
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possible decrease in aggression
 Always
rule out treatable cause
 Consider 3 mon trial of cholinesterase
inhibitor
 Re-evaluate meds often (q3-6mons)
 If delusions/hallucinations, only treat if a
threat to self/others, or interfere w/ care
 AVOID POLYPHARMACY– proven that the more
pills, the worse they feel and behave
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Stop all unnecessary medications
 Focus
on TLC!
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Diagnosis of probable Alzheimer’s as per DSM-IV
Mild to moderate stage of disease, with MMSE of 1026/30, <60 days of application
FAQ <60 days of application
Must discontinue all drugs with anticholinergic activity,
at least 14 days before MMSE and FAQ given.
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No concurrent anticholinergic therapy. Patients intolerant
to one agent may be switched to a different agent.
Current Patients: Require 6 months assessment to
continue, must not have both a >2 point reduction in
MMSE and a 1 point increase in FAQ. Scores are
compared to previous scores.
New Patients: Enter 3 month trial and must exhibit
improvement in MMSE and FAQ scoring. RE-evaluate in 6
months as above.
 MMSE
must stay at or above 10 throughout
treatment
 The patient is monitored with these 2 scales
(MMSE , FAQ) to ensure treatment is still
effective. Once the patient is not
responding to the medication (scores worsen
with set guidelines, MMSE 2 point reduction,
FAQ 1 point increase) coverage is stopped.
The risk of treatment then outweighs the
benefit and treatment is stopped.
Therapeutic Choices, 5th Edition
 Alzheimer’s Society of Canada
http://www.alzheimers.ca/english
 RX Files
 Rhett Carbno, College of Pharmacy Lecture
Notes on Dementia.
 Robert J. Webb, MD. Medical Director, Hospice
of the Shoals, and Palliative Care Service, ECM
Hospital. Florence, AL. Drugs for Dementia
Lecture. March 11-12th, 2011.
 Dementia Guide
http://www.dementiaguide.com/aboutdementia
/typesofdementia/alzheimers
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