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how is dementia characterized
- impaired memory and one of the following
- aphasia
- apraxia
- agnosia
- executive function
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cholinesterase inhibitors
- donepezil - aricept
- rivastigmine - exelon
- galantamine - razadyne
- tacrine - cognex
-
NMDA receptor antagonist
memantine - namenda
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which meds are used for mild - moderate AD
- donepezil - aricept
- rivastigmine - exelon
- galantamine - razadyne
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which meds are used for moderate-severe AD
- donepezil - aricept
- memantine - namenda
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the most frequent adverse effects of cholinesterase inhibitor
mild to moderate GI
-
tacrine - cognex limiting adverse effect and a drug interaction cause
- hepatotoxicity - occurs early
- substrate of CYP 1A2
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which med is 1st line therapy and approved for severe AD dementia
donepezil (Aricept)
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donepezil (Aricept) MOA
specifically and reversibly inhibits acetylcholinesterase
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donepezil (Aricept) adverse effects
-
rivastigmine (Exelon) MOA
inhibits acetyl and butyryl cholinesterase
-
which acetylcholinesterase inhibitor comes in a transdermal patch
rivastigmine - exelon
-
which AChEI is not metabolized by CYP450
rivastigmine - exelon
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which med is indicated for PD dementia
rivastigmine - exelon
-
galantamine (razadyne) MOA
- selective, competitive, reversible AChEI
- nicotinic receptor agonist
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5 scenarios when cognitive enhancing medications might be stopped
- poor quality of life
- AE's intolerable
- improvement not seen with therapeutic doses
- pt is bedridden and unable to perform ADL's
- slowing disease progression is no longer a goal
-
memantine - Namenda MOA
blocks glutamatergic neurotransmission by antagonizing NMDA receptors
-
A DI of memantine (Namenda)
- clearance decreases by 80% when urinary pH >8
- caution with carbonic anhydrase inhibitors
- sodium bicarb
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2 statins that show a lower prevalence of AD
-
rember - methylene blue MOA
dissolves tau tangles and prevents formation of new tangles
-
new drug with a MOA of "plaque buster"
PBT2 - attacke beta-amyloid 42
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new drug with a MOA of mitochondrial health and an antihistamine
latrepirdine - dimebolin
-
studied drug that treats the agitation in AD
- AVP-23 (dextromethorphan & quinidine)
- dex works on NMDA receptor
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what is BPSD in AD
behavioral and psychological symptoms of dementia
-
where do antipsychotics stand in the tx of BPSD
may tx symptoms but not indicated for mgmt. of behavioral symptoms in AD and there is a risk of death
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6 types of dementia
- AD
- vascular
- lewy body
- Parkinson's
- frontotemporal - responds poorly to meds
- reversible
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7 drugs and toxins that can cause dementia symptoms
- anticholinergics
- antihypertensives
- anxiolytic/sedatives
- alcohol
- hypoglycemics
- heavy metals
- CNS depressants
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4 systemic illness' that can cause dementia symptoms
- cardiovascular disease
- B12 & folate deficiency
- infection
- metabolic disorders
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do cognitive impairments warrant a diagnosis of dementia
no but there is a 10-15% chance per year of progressing to AD diagnosis
-
where does AD rank in causes of death and some trivia
- 5th
- 3-20 year survival
- 42% incidence at 85 years and older
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6 risk factors for dementia
- genetics
- family history
- age/gender
- mild cognitive impairment
- risk factors for vascular diseae
- lifestyle and activity
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what are the genetic links for AD
- early onset = chromosomes 1,14 or 21
- late onset (sporadic) linked to APO E4
- 40% have one copy
- 90% with 2 copies will develop AD by age 80
- you can have Apo E4 and not develop AD
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what are the neurotransmitter abnormalities in dementia
- decreased ACh synthesis
- increased glutamate
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what neurologic transformation happens in AD
hippocampal shrinking
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examples of complex ADL and what they are associated with
- telephone use
- shopping
- cleaning
- using TV/Radio
- more associated with executive function
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how do you get a definitive diagnosis of dementia
brain tissue exam
-
some clinical diagnosis for dementia
- interview pt, family, caregiver
- full medical history
- physical exam
- neuropsychological screening
- neuroimaging - PET scan, MRI
- serologic and CSF evaluation
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tests used to identify cognitive dysfunction
-
test used to evaluate severity of dysfunction in AD
ADAS - Alzheimer's disease assessment scale
-
3 phases of AD
- asymptomatic, preclinical phase
- symptomatic, pre-dementia phase (MCI)
- dementia phase
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features of very mild cognitive decline
forgetfulness, subjective complaints only
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features of mild cognitive decline
- objective decline(tests) mild anxiety and denial
- work/social impairment
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features of moderated cognitive decline
concentration, complex skill decline, withdrawal
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features of moderately severe cognitive decline
early dementia, difficulty in interactions
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features of severe cognitive decline
assistance with bathing, behavioral symptoms present
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features of very severe cognitive decline
total dependence
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some nonpharm therapy for dementia
- make things simple and make the pt safe
- exercise
- mental stimulation - and new challenges
-
donepezil - Aricept dosing
5-10 mg QD
-
rivastigmine - Exelon dosing
- 1.5 mg BID - starting
- 3-6 mg BID
-
galantamine - razadyne dosing
- 4 mg BID starting
- 12 mg BID
-
tacrine - cognex dosing
- 10 mg QID starting
- 160 mg/day
-
memantine - Namenda dosing
- 5 mg day starting
- 10 mg BID - increased weekly to get there
-
max dose of vitamin E
400 iU/day
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