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Alzheimer’s Disease. By: Carla Alexander, 4 th Year Pharmacy Student March 17 th , 2011. Overview. Definition Prognosis Pathophysiology Symptoms Treatment Functional Tests Exceptional Drug Status . Types of Dementia. Dementias: Alzheimer’s Disease Vascular Dementia

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alzheimer s disease

Alzheimer’s Disease

By: Carla Alexander, 4th Year Pharmacy Student

March 17th, 2011

  • Definition
  • Prognosis
  • Pathophysiology
  • Symptoms
  • Treatment
  • Functional Tests
  • Exceptional Drug Status
types of dementia
Types of Dementia
  • Dementias:
    • 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:
    • Memory
    • Emotion
    • Language
    • Eye-hand skills
    • Executive function (planning or completing activities
  • Impairment of cognitive function is sufficient to interfere with normal daily activities.
characteristics of alzheimer s disease
Characteristics of Alzheimer’s Disease
  • 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
    • 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
  • 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

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.

  • Three 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

90% of patients have behavioural and psychological symptoms

  • Currently, once an ability is lost, it won’t return.
  • No known, single cause of Alzheimer's disease.
  • However:
    • 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 treatable causes
Rule out Treatable causes
  • 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
  • Depression (Pseudo-dementia)
  • Delirium (drugs, infections-UTI causes delirium)
    • first check urine
  • Hypothyroidism
  • Vit. B12 deficiency
  • Alcoholism
  • Drugs & polypharmacy
  • Hard of hearing
functional tests
Functional Tests
  • Cognitive impairment assessed using Mini-Mental State Examination (MMSE)
    • Orientation, learning, naming, drawing, judgment skills, clock drawing
  • Functional disability is measured with Functional Assessment Staging Tool (FAST), or Functional Activities Questionnaire (FAQ)
    • FAQ is required by SK drug plan
    • Rates 10 routine activities from normal (0) to dependent (3)
    • Lower the score, the better
staging severity
Staging Severity
  • Mild
    • 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
    • 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.
staging severity1
Staging Severity
  • Severe
    • 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.
non pharmaceutical treatments
Non-Pharmaceutical Treatments
  • Often sufficient to make a noticeable improvement in the target symptoms
    • 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 non-pharmacological interventions have failed or in situations with dangerous risk,(agitation, hitting).
pharmacological treatment
Pharmacological Treatment
  • 2 classes of pharmacological agents:

1. Primary meds which attempt to slow the progression

    • Cholinesterase inhibitors
    • Memantine

2. Symptomatic meds to manage secondary complications (depend on stage of progression)

    • Antipsychotics
    • Antidepressants
    • Benzodiazepines
    • Hypnotics
    • Anxiolytics
    • Mood Stabilizers
    • Reevaluate all drug therapies q3- 6 mons to see if still indicated
primary cholinesterase inhibitors
Primary: Cholinesterase inhibitors
  • 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.
cholinesterase inhibitors
Cholinesterase inhibitors
  • Might slow the decline rate – 3-4% over 6 months
    • Benefits are small, disease stabilization
    • No effect on agitation
  • Trial prescription for ~3months for effect
    • 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
    • GI issues!, n/v, fatigue, anorexia, decreased heart rate, insomnia,
  • Expensive ($172-230/month)
  • EDS coverage
  • Does not delay institutionalization
primary memantine
Primary: Memantine
  • 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 
symptomatic treatment
Symptomatic Treatment
  • Treats the behavioural & psychological component
    • Hyperactivity = irritable, restless, disinhibition
    • Mood & apathy = anxiety, depressed, no appetite
    • Psychosis = delusions, hallucinations, anxiety
agitation antipsychotics
  • 2nd generation antipsychotics:
    • risperidone (Risperdal)
    • olanzapine (Zyprexa)
    • quetiapine (Seroquel)
    • aripiprazole (Abilify)
  • 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
agitation antidepressants

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
    • Sedating side effect, good for insomnia
    • Also used to treat sundowning
    • 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
anxiety benzodiazepines bzd
Anxiety—Benzodiazepines (BZD)
  • 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
  • Sedating antidepressant may be helpful(Trazodone)
  • Only use hypnotics when absolutely required.
  • Good alternative is zopiclonevs BZD
other drugs
Other drugs
  • 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
    • 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
    • Stop all unnecessary medications
  • Focus on TLC!
eds cholinesterase inhibitors
EDS- Cholinesterase inhibitors
  • Diagnosis of probable Alzheimer’s as per DSM-IV
  • Mild to moderate stage of disease, with MMSE of 10-26/30, <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.
    • 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.
eds continued
EDS continued:
  • 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
  • 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