Alzheimer's Disease Flashcards
what is the DSM-5 criteria for Alzhiemer’s disease
- evidence of sig cognitive decline from prior level of performance in >/= 1 cognitive domains (complex attention, executive function, learning & memory, language, perceptual-motor/social cognition
- cognitive deficts interfere with independence in everyday activities
- cognitive deficits do not occur exclusivelt in context of delirium
- cognitive deficits are not better explained by another mental disorder
what is the pathologic characteristic of AD?
brain atrophy esp in mesial temporal lobe, beta-amyloid & neurofibrillay tangles
what is the onset & course of AD
slow onset, gradually over months to years
what are the non-modifiable risk factors for AD?
- age (5-65% in >65, 50% in >85)
- female
- ethnicity (black, hispanic)
- genetics (APOE4)
what are the modifiable risk factors for AD?
- diabetes
- HTN
- smoking
- obesity
- limited physical activity
- binge drinking
- depression
- hearing loss
how is AD diagnose?
- medical hx
- physical exam
- neuropsychological testing
- lab test - rule out other medical condition
- imaging of brain (CT/MRI)
what is the pathophysology of AD?
- accumulation of Abeta –> form amyloid plaques –> activate microglia to clear them –> inflammation & damage to the axons
- neurofibrillary tangles (NFT): abnormal hyperphosphorylated tau protein –> accumulate in synaps
as disease progress, widespread damage & degeneration of neurons
what is the goal of treatment?
reduce suffering caused by cognitive & accompanying symptoms (eg mood & behaviour), while delaying progressive cognitive decline
what pharmacological treatment are there for AD?
- anticholinerase inhibitors (AI)
- NMDA receptor antagonist (memantine)
what is the MOA for anticholinesterase inhibitors?
inhibit acetylcholinestearse enzyme –> promote increase in acetylcholine at synpatic cleft for cholinergic neurotransmission
how should anticholinesterase inhibitors be titrated?
titrate slowly over 4-8 weeks to reach target dose & minimize side effects
if adverse effects occur, lower the dose temporarily before reescalating more slowly & monitor for adverse effects
alternatively, discontinue & switch to different AI
how should anticholinesterase be monitored?
monitor for any improvement in day-to-day life
routine cognitive test (eg MoCA)
what is the MOA for memantine
uncompetitve antagonist of NMDA type of glutamate receptors
glutamate: primary excitatory amino acid in CNS, may contribute to pathogenesis of AD by overstimulating various glutamate receptors –> excitatory & neuronal cell death
when is memantine considered?
- mod-severe AD
- cannot tolerate AI
what should be monitored when on memantine?
- cognitive feedback (any improvement in day-to-day activities?)
- routine cognitive tests
what are the 3 anticholinesterase inhibitors available?
- donepezil
- galantamine
- rivastigmine
when is anticholinesterase inhibitors used?
monotherapy for mild to moderare alzhiemer disease
when is memantine used?
moderate AD if intolerant/contraindication to acetylcholinesterase inhibitors
severe AD
can consider adding on to AI if have moderate disease & taking AI
add on to AI if severe
non-pharmacological approaches for AD?
- cognitive stimulating activities
- physical exercise
- social interactions
- healthy diets
- adeuqate sleep
- proper personal hygiene
- safety inside & outside home
- medical & advanced care directives
- long-term health care planning in late stage of AD
- financial planning
- effective communication
- psychological health
what does BPSD stands for?
behavioural & psychological symptoms (BPSD)
what is BPSD?
involve non-neurological & non-cognitive symptoms, eg aggitation, aggression, psychosis, depression, apathy
if pharmacological treatment is indicated, for BPSD what can be used?
- anticholinesterase inhibitors (donepezil)
- memantine
- SSRI, mirtazapine
- lorazepam
- antipsychotics (first line olanzapine, quetapine, risperidone, aripiprazole, clozapine)
nonpharmacological approach for BPSD?
- understand pt background –> insight to potential causes & solutions
- understand rs btw person w dementia & carer & stresses that the condition is placing on both
when is pharmacological treatment indicated for BPSD?
have limited role, consider adverse effects & indication for use
1. prescribe for target symptoms/behaviours for which there is evidence of effectiveness (should not be used for other indication/sedate pt)
2. only consider once potentially reversible causes have been excluded & non-pharmacological interventions have been trialled; unless there is an immediate risk to the patients or others, or pt severely distress
3. combi with non-pharmacological interventions
4. initiate as trial, not indefinitely without need, review response, dose & adverse effect at least every 3month
5. rountinely withdrawn, slowly aft 3 months of improved symptoms unless symptoms severe
6. restart at lowest effective dose if symptoms return, schedule trial 3-6 months
drug for depressive symptoms?
SSRI - effective for depression & anxiety
citalopram - can reduce agitation, improve symptoms. but can cause dose-dependent risk of increased QTc prolongation & worsening cognition needs
TCA - not prescribed, anti-cholinergics
when are antipsychotics used?
for aggression, agitation, psychotic symptoms causing severe distress/immediate risk of harm to pt/others
modest effective
increase risk of stroke, CV events, excess mortality
adverse effects for amyloid monoclonal antibodies?
edema
hemorrhage
