11 - Alzheimer's Disease

Question 1

Dementia

Answer 1

• A group of disorders characterized by a progressive non-reversible loss of cognitive function
• Memory loss, performing familiar tasks, language, etc.
• Dementia types differ by:
• • Sx onset and type
• • Response to tx
• Can have a mix of various dementias

Question 2

What are some examples of normal aging memory loss?

Answer 2

• Details of an event that took place a year ago
• Acquaintance name/face
• Occasionally forget things
• Worried about your memory but relatives aren’t

Question 3

What are some examples of dementia memory loss?

Answer 3

• Details of recent events
• Family member name/face
• Frequently forget things
• Relatives are worried about memory but you are unaware

Question 4

Briefly describe the brain and Alzheimer’s disease

Answer 4

• Most people undergo a gradual cognitive decline over their life span
• 100 billion neurons and 100 trillion synapses
• To stay healthy, neurons must communicate w/ each other, carry out metabolism, and repair themselves
• Alzheimer’s disease disrupts all 3 of these essential jobs

Question 5

Describe “three pounds, three parts”

Answer 5

1. Cerebral hemispheres
   - Process sensory info
   - Voluntary movement
   - Regulates conscious thought
2. Cerebellum
   - Balance and coordination
3. Brain stem
   - Connects brain and spinal cord
   - Controls automatic functions (ex: HR, BP, breathing, digestion)

Question 6

Compare and contrast normal function vs. Alzheimer’s in the frontal lobe

Answer 6

• Normal = plan and initiate activity, judgement/ behaviour

- AD = apathetic, withdrawn

Question 7

Compare and contrast normal function vs. Alzheimer’s in the limbic lobe

Answer 7

• Normal = emotions, basic needs (sleep/ eat)

- AD = suspiciousness, irritability, mood/ anxiety

Question 8

Compare and contrast normal function vs. Alzheimer’s in the hippocampus/ temporal lobe

Answer 8

• Normal = short-term memories converted to long-term memories
• AD = inability to retain memory of recent past, recognize objects

Question 9

Compare and contrast normal function vs. Alzheimer’s in the parietal lobe

Answer 9

• Normal = puts activities in sequence, spatial information

- AD = using words incorrectly, getting lost easily, dressed

Question 10

Describe what occurs in the brain during Alzheimer’s dementia

Answer 10

• The brain in Alzheimer’s disease has fewer nerve cells and synapses than a healthy brain
• Hallmarks of Alzheimer’s disease = neuritic plaques and neurofibrillary tangles
• Central atrophy (brain shrinkage)
• Net result = decrease in multiple NTs (cholinergic system appears most significantly affected)

Question 11

Neuritic plaques

Answer 11

• Plaques are formed from protein pieces (called beta-amyloid) that “stick” together
• Block cell-to-cell signaling at synapse

Question 12

Neurofibrillary tangles

Answer 12

• Tangles are collapsed and twisted fibers of protein (called tau) build up inside the nerve cell
• Tau helps stabilize the cell transport system that allows nutrients, cell parts, and other essential materials to move through the cells
• W/o this system, the nerve cells eventually die

Question 13

NT changes in Alzheimer’s

Answer 13

• Reduced activity of choline acetyltransferase
• Selective loss of certain nicotinic receptor subtypes
• Reduced # of cholinergic neurons

Question 14

Diagnosing AD

Answer 14

• Detailed pt hx w/ info from caregiver
• • Caregivers w/o pt present may allow for truthful hx
• • Include comorbid conditions and medications
• Cognitive status (brief cognitive tests)
• Physical & neurological exams and lab tests (to rule out other conditions)
• Behavioural sx, daily functioning
• Imaging (CT scan, MRI, PET) to rule out vascular disease

Question 15

Precipitating factors for AD

Answer 15

• Drugs (sedative hypnotics, narcotics, anticholinergics)
• Primary neurologic disease (stroke, intracranial hemorrhage, meningitis)
• Intercurrent illness
• Surgery
• Environment (admission to ICU, use of physical restraints, bladder catheter, pain, emotional stress, prolonged sleep deprivation)

Question 16

Drugs that can cause/ contribute to cognitive impairment

Answer 16

• Anticholinergics –> TCAs (paroxetine), anti-emetics, antihistamines (1st gen), antipsychotics, ranitidine
• Psychoactive –> alcohol, anticonvulsants, antidepressants, antipsychotics, lithium, muscle relaxants, opioids
• Other –> cipro, clarithro, corticosteroids, digoxin, NSAIDs

Question 17

Brief cognitive tests (MMSE or MoCA)

Answer 17

• Lack of evidence to recommend one over the other
• Not used to differentiate between dementia subtypes
• Used because:
• • Required for drug benefit programs (part 3 EDS)
• • Help inform clinical judgement
• • Provides objective measure vs. qualitative assessments

Question 18

MMSE (mini-mental state exam)

Answer 18

• Most widely used instrument to estimate severity and to monitor change in cognitive impairment during therapy
• Score of 10-26 required for anticholinesterase drug coverage; score < 24 typically included in AD RCTs
• Normal = 1-2 point drop/year
• Untreated AD = 2-4 drop/year
• Strengths –> quick to administer, easy to use, established validity
• Limitations –> not sensitive for detecting mild dementia, score influenced by age, education, language, inattention, motor/ visual impairment

Question 19

MoCA (montreal cognitive assessment)

Answer 19

• Alternative instrument used in clinical practice validated in px 55-85 y/o
• Average MoCA for mild cognitive impairment (MCI) = 22 (19-25)
• Average MoCA for mild AD = 16 (11-21)
• AD = cognitive impairment (MoCA < 10) + loss of autonomy

Question 20

Stages of dementia

Answer 20

• Early/ mild (1-3 years from sx onset)
• Moderate (2-8 years from sx onset)
• Severe (6-12 years from sx onset)

Question 21

Drug tx for cognitive sx of AD

Answer 21

• Cholinesterase inhibitors (donepezil, rivastigmine, or galantamine)
• NMDA antagonist (memantine)
• Mild to moderate = cholinesterase inhibitor; moderate to severe = add anti-glutamatergic (memantine)

Question 22

Goals of therapy for Alzheimer’s

Answer 22

• Treat sx of cognitive difficulties
• Preserve pt function
• Treat psychiatric and behavioural sequelae
• *Current tx have not been shown to prolong life, cure dementia, or stop/reverse the pathophysiologic processes of dementia

Question 23

Pt and caregiving counselling for Alzheimer’s

Answer 23

• Currently no cure for AD exists
• Cholinesterase inhibitors
• • Modest benefit in stabilizing/ slowing progression of AD
• • May help w/ deficits in memory, language, and thinking abilities; not all px respond
• • SE = GI, fall risk, urinary incontinence; titrate dose to minimize
• Evaluate medications that can further compromise cognitive function
• *Decision to initiate therapy should be made after a detailed discussion w/ pt & caregiver

Question 24

Cholinesterase inhibitors - MOA, indication, SE, choosing one over the other, contraindications

Answer 24

• Donepezil, rivastigmine, galantamine
• MOA –> increase availability of ACh at synapse
• All 3 indicated as acceptable initial monotherapy for mild to moderate AD (donepezil also indicated for severe AD)
• All 3 demonstrate similar benefit/ stabilization of AD for 6-9 months, followed by gradual decline
• Limited data on relevant outcomes (ex: function, behaviour, caregiver burden, QOL); no delay in institutionalization
• Choice based on ease of use, pt preference, cost, safety issues
• Most common SE = dose-dependent GI (N/V, diarrhea) most likely to occur at start of tx or dose escalation; longer titration and administration w/ food will help
• Relative contraindications based on conditions affected by increasing cholinergic tone
• • Cardiac conduction abnormalities, bradycardia
• • Active PUD (PPI may be protective)
• • Asthma/ COPD (avoid in uncontrolled lung disease)
• If d/c, taper by 25-50% q1-2w to minimize risk of rebound constipation & other SE

Question 25

Memantine - MOA, indication, SE

Answer 25

• NMDA antagonist
• Not recommended for mild dementia
• Option as monotherapy or combo tx w/ cholinesterase inhibitors for moderate to severe AD
• Caution in seizures and CV disease
• SE = dizziness, constipation, confusion, headache, HTN

Question 26

Behavioural and psychological sx of dementia (BPSD)

Answer 26

• High prevalence in AD (70-90% of px)
• Verbal abuse
• Most common reason for placement
• BPSD behaviours include depression, anxiety (caution w/ BZDs), psychosis, agitation (wandering, uncooperative, aggression, pacing)
• Triggers = sensory deficits (poor eyesight/ hearing), SE of some meds, psychiatric illness, unfamiliar environment, physical conditions

Question 27

Non-drug approaches for Alzheimer’s

Answer 27

• 1st line for non-threatening & stressful behaviours
• Environment –> ABC charting, reduce noise, keep area well lit
• • ABC charting –> Antecedents (causes) = PIECES (physical, intellectual, emotional, cultural, environmental, social); behaviours; consequences
• Activities –> schedule activities the pt enjoys throughout the day, discourage naps throughout the day, music therapy
• Pt/caregiver interactions –> calm demeanor & well-paced, quiet tone, refocus & redirect the pt as needed, caregiver education critical

Question 28

Antipsychotics in dementia

Answer 28

• Modest effect for BPSD
• Serious adverse effects (death, stroke)
• Avoid use; potentially appropriate in hallucinations, delusions, or aggressive behaviour
• • Appropriate if sx presents a danger to pt or others

Question 29

Delirium vs. dementia

Answer 29

• Delirium = acute and abrupt onset, fluctuating course, possibly reversible, alertness and vitals are decreased/altered
• Dementia = chronic onset, duration progressive and continuous, progressive decline, non-reversible, alertness and vitals are normal

Question 30

Other drugs for AD? (estrogen, NSAIDs, statins, NHPs)

Answer 30

• Estrogen –> observational studies show lower incidence in AD w/ estrogen use; not recommended
• NSAIDs –> not recommended b/c of SE & lack of evidence
• Statins –> no evidence to prove they are helpful; only recommended for px who have other indications for statin use
• • Cognitive impairment recognized as a rare adverse event associated w/ statin in case reports
• No NHPs are recommended (vitamin E, gingko biloba, polyphenol/ resveratrol)