Alzheimer's Disease Flashcards
What is the DSM-IV-TR Criteria for Dementia?
- Memory Impairment (learning new info and recalling old)
AND - One of the following:
- Aphasia (language disturbance)
- Apraxia (impaired motor activity ability)
- Agnosia (failure to recognize objects)
- Disturbance in executive functioning (planning, organizing, sequencing, abstracting)
What is the DSM-V Criteria for Major Neurocognitive Disorder?
Evidence of significant cognitive decline from a previous level of performance in one or more area of cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor or social cognition) based on:
* Concern of the individual, a knowledgeable informant or the clinician that there has been a significant decline in cognitive function
AND
* Substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing, or in its absence, another quantified clinical assessment
What are some symptoms and behaviors in dementia?
- Memory loss
- Poor judgement
- Diminished driving skills
- Disorientation and unadaptability
- Personality change and disinhibition
- Communication disorders
- Demanding and repetitive behaviors
- Emotional lability and depression
- Diminished self care skills
- Insomnia and sundowning
- Wandering and falling
- Aggressiveness and catastrophic reactions
- Delusions and hallucinations
- Incontinence
- Late gait disturbances and immobility
Multi-Infarct Dementia
- Abrupt
- Deterioration: Step-wise
- PMHx: HBP/ASCVD/CVD
- ROS/PE: Focal Neuro exam
Alzheimer’s Type
- Insidious
- Deterioration: Slow, progressive
- PMHx: Non-cardiac dz
- ROS/PE: Non-focal neuro exam
What are the most common reversible causes of dementia?
- Drugs
- Depression
- Metabolic
What are the drug classes associated with cognitive impairment in the elderly?
- Anticholinergics
- Anticonvulsants
- Antihistamines
- Antiparkinson
- Analgesic
- Cardiovascular
- Gastrointestinal
- Psychotropics
What are the highest risk anticholinergic drugs?
- Amitriptyline
- Atropine
- Benztropine
- Carisoprodol
- Dicyclomine
- Diphenhydramine
- Hydroxyzine
- Meclizine
- Oxybutynin
What are the high risk anticholinergics?
- Amantadine
- Baclofen
- Cimetidine
- Cyclobenzaprine
- Loperamide
- Nortriptyline
- Tolterodine
Dementia vs Delirium
- Decline in cognitive function over time
- Memory loss
- Short period of time (hours to days)
- Acute change in level of consciousness
- Decline in cognition
What are the risk factors of AD?
- Old age ( > 65 years)
- Female (2x W>M)
- Positive family history (Apolipoprotein E4 allele)
What are the early-mid cognitive symptoms of AD?
- Memory deficits
- loss of inhibitors
- naming difficulties
- problems with IADLs
- social withdrawal
What are the later-moderate cognitive symptoms of AD?
- Comprehension difficulties
- problems dressing
- grooming
- feeding
- delusions
- agitation
- aggression
- disorientation
- wandering
- sleep abnormalities
What are the end-severe cognitive symptoms of AD?
- Rigidity
- bedridden
- myoclonic jerks
- hyperactive reflexes
- mute
- incontinent
- death
What is the pathophysiology of AD?
- Destroys acetylcholine synthesizing neurons (hippocampus & cortex)
What are the four alterations of AD?
- Extracellular B-amyloid plaques
- Intracellular neurofibrillary tangles
- Degeneration B-amyloid plaques
- Cortical atrophy
What are the assessments for AD?
- Diagnosis of exclusion-confirmed on autopsy
- Folstein Mini-Mental Status Exam (MMSE) or Montreal Cognitive Assessment
- Alzheimer’s Disease Assessment Scale (ADAS-Cog)
- Clinician’s Interview Based Impression of Change (CBIC-Plus)
Which drugs are cholinesterase inhibitors?
- Tacrine
- Donepezil
- Rivastigmine
- Galantamine
What is the MOA of cholinesterase inhibitors:
Inhibits acetylcholinesterase preventing hydrolysis of acetylcholine, thus increasing acetylcholine in the synaptic cleft
What is the MOA of Tacrine (Cognex)?
Centrally acting, competitive, reversible BChE > AChE
What is the place of therapy of Tacrine (Cognex)?
- First cholinesterase inhibitor
- FDA approved in 1993
- FDA approved – mild to moderate AD
What are the adverse effects of Tacrine (Cognex)?
- Cholinergic SE
- Hepatotoxicity – no longer marketed
- LFT monitoring (50% elevated LFTs)
What are some drug interactions of Tacrine (Cognex)?
- Decreases theophylline metabolism
- Cimetidine decreases tacrine metabolism
What is the MOA of Donepezil?
Competitively binds AChE
What is the place of therapy of Donepezil?
- Second generation Cholinesterase inhibitor
- FDA approved in 1996
- FDA approved indications: mild, moderate, and severe AD
What is the dosing of Donepezil?
- Mild to moderate AD dosing: 5 mg once daily; may increase to 10 mg daily after 4-6 weeks; range 5-10 mg/day
- Moderate to severe AD dosing: 5 mg once daily; may increase to 10 mg daily after 4-6 weeks; may increase further to 23 mg once daily after ≥ 3 months; range 10-23 mg/day
What is the adverse effects of Donepezil?
(>10%)
* CNS: Insomnia (may need to switch dosing time)
* GI: Nausea, diarrhea (dose-related)
May diminish over time
What are some drug interactions of Donepezil?
- Anticholinergics
- Beta-blockers
- St. John’s Wort (decreased donepezil levels)
Monitor for HR (may cause bradycardia)
What is the place of therapy of Rivastigmine?
- FDA approved indications: mild to moderate AD
- Mild-moderate dementia associated with Parkinson’s dz
What is the MOA of Rivastigmine?
- Pseudoirreversible agent that inhibits centrally acting AChE > peripheral AChE
- Inhibits BChE
What is the dosage of the transdermal patch of Rivastigmine?
4.6 mg/24 hours, if well tolerated, may be increased after 4 weeks to 9.5 mg/24 hours
What is the conversion from oral Rivastigmine to the patch?
- If daily dose < 6 mg, switch to 4.6 mg/24 hour patch
- if dose 6-12 mg, switch to 9.5 mg/24 hour patch
What are the adverse effects of oral Rivastigmine?
(>10%)
* CNS: Dizziness and headache
* GI: Nausea, vomiting, diarrhea, anorexia, abdominal pain
What are the adverse effects of transdermal Rivastigmine?
- N/V/D (may be less)
- Extrapyramidal sx (particularly tremor)
What are some clinical pearls of oral Rivastigmine?
Should be administered with meals (breakfast or dinner)
What are some drug interactions of Rivastigmine?
Anticholinergics and beta blockers
What is the disadvantage of Rivastigmine?
- BID dosing
- Longer titration period
What is the proper patch use of Rivastigmine?
- Apply 1 patch each day to intact, healthy skin on the upper arm chest, or upper or lower back
- After 24 hours, remove existing patch and apply new patch to a different skin location (avoid reapplication to the same spot for 14 days)
- Patches should NOT be cut into pieces
- After removal, fold patch to press adhesive surfaces together, and discard
What is the MOA of Galantamine (Razadyne)?
Reversible inhibition of acetylcholinesterase
What is the place of therapy of Galantamine (Razadyne)?
- FDA approved February 2001
- New trade name Razadyne® July 2005 – to avoid confusion with Amaryl®
- FDA approved indications: mild to moderate AD
What are the adverse effects of Galantamine (Razadyne)?
N/V/D
What are the counseling points of Galantamine (Razadyne)?
- Oral soln or tablet with breakfast and dinner
- ER cap with breakfast
- Mix oral soln with 3-4 oz. of any nonalcoholic bev, mix well and drink immediately
What is the MOA of Memantine?
- NMDA receptor antagonist
- Glutamate activates NMDA receptor which is involved in learning and memory. Blocking NMDA may prevent further damage
- Abnormal glutamatergic activity leads to sustained low level activation of NMDA receptors
- Leading to neuronal damage/loss and cognitive deficits
What is the place of therapy of Memantine?
Moderate to severe AD (literature also supports add-on therapy with donepezil)
What are the adverse effects of Memantine (Namenda)
(1-10%; rated as mild or moderate)
* CNS: Dizziness, headache, somnolence
* GI: Constipation, diarrhea, vomiting
What are the drug interactions of Memantine (Namenda)?
- Elimination: Primarily unchanged in urine
- Trimethoprim – may INCREASE serum conc of memantine, INCREASE risk of myoclonus and delirium
Memantine + Donepezil (Namzaric)
- Moderate to severe AD
- Should be stabilized on donepezil 10 mg/day before starting
What are the drug interactions of Memantine + Donepezil (Namzaric)?
- Anticholinergics
- Beta blockers
- Trimethoprim
Aducanumab (Aduhelm)
- Removed from the market February 2024
- Patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease
- Mechanism – anti-amyloid antibody
- ADE: “ARIA”
Lecanemab (Leqembi)
- Indicated for patients with mild cognitive impairment or mild dementia due to Alz dz (early stage)
- Adverse effects: ARIA-E (10%), ARIA-H (6%), and infusion reactions (20%)
What are some behavioral and psychological symptoms of dementia (BPSD)?
- Sundowning
- Psychosis (7-33%), delusions (30-70%)
- Sleep disturbances (25-35%)
- Restlessness, combativeness
- Wandering, hoarding
- Hypervocalization
- Aggression, agitation
- Hypersexuality
What are some BPSD Pharmacological Options?
- Antipsychotics
- Antidepressants (SSRIs)
- Antiepileptics (Carbamazepine, Valproate)
- Benzodiazepines
What are some atypical antipsychotics?
- Risperidone
- Quetiapine
- Olanzapine
- Ziprasidone
- Aripiprazole
What are some FDA warnings/issues of atypical antipsychotics?
- Metabolic
- Cardiac conduction - Prolonged QT interval (Ziprasidone is the worst)
- Mortality and stroke risk
Which atypical antipsychotics are preferred?
- Quetiapine and Olanzapine (low dose)
