Term
intellectual deterioration severe enough to impede social or occupational performance
insidious onset with gradual deterioration |
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Definition
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Term
ACUTE confusional state
acute onset with clouding of consciousness |
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Definition
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Term
| characteristics of cortical dementia |
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Definition
AD is a type of cortical dementia
amnesia
cognitive deficits (judgment, calculation)
unconcerned affect
language deficits with normal articulation
normal motor function |
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Term
| characteristics of subcortical dementia |
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Definition
parkinson's disease and huntington's disease are a type of subcortical dementia
forgetful
slow cognition
apathetic or depressed affect
dysarthric/hypophonic speech
abnormal motor signs |
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Term
| risk factors for Alzheimer's disease |
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Definition
advanced age
family history of dementia
genetic factors in early-onset disease |
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Term
| genetics of early onset AD and late onset AD |
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Definition
early onset AD is rare:
chromosome 21 - amyloid precursor protein (Down's syndrome - trisomy 21)
chromosome 14 - presenilin 1
chromosome 1 - presenilin 2
late onset AD:
chromosome 19 - Apolipoprotein E4
heterozygote risk increased 2-4 fold
homozygote risk increased 5-18 fold |
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Term
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Definition
cerebral atrophy - not specific for AD
neuronal loss
senile plaques: beta-amyloid
amyloid precursor protein (APP) is cleaved to form beta-amyloid
beta-amyloid aggregates in pleated sheets to form plaques
gene encoding for APP is found on chromosome 21 (Down's syndrome)
link between beta-amyloid, plaque formation, nerve degeneration, and cell death is missing
neurofibrillary tangles: ApoE4
ApoE has 3 variants: 2, 3, and 4
ApoE3 is the more common and beneficial - maintains structure of nutrient transporting protein tau
ApoE4 does not bind to tau - those with ApoE4 appear to be at higher risk for developing AD
those with ApoE2 appear to be protected |
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Term
| biochemical changes in AD |
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Definition
decrease in choline acetyltransferase (enzyme of the rate limiting step of the production of Ach): strong association with memory impairment, similar memory impairment with anticholinergics
norepinephrine
serotonin
glutamate |
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Term
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Definition
memory impairment (short-term)
cognitive deficits (calculation, judgement, abstraction)
geographic and temporal disorientation
word-finding difficulties
difficulty with ADLs and IADLs
anxiety or depression
behavior problems: agitation, hallucinations, delusions
total dependence |
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Term
| differential evaluation of dementia |
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Definition
other causes of dementia: vascular, Pick's, Creutzfeldt-Jakob, NPH, Parkinson's tumors
vitamin deficiencies: B12 (gastric acid needed for the proper absorption of B12), folate (rare)
thyroid disorders (HYPOthyroidism)
neurosyphilis, AIDS
depression (pseudodementia - depression is affected the person's cognition)
drugs |
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Term
| drugs that can induce cognitive impairment |
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Definition
benzodiazepines: lorazepam, diazepam
anticholinergics
psychotropics: TCAs, anti-psychotics, anti-anxiety medications)
antihypertensives: methyldopa, clonidine (centrally acting anti-hypertensives, not ACEi or CCBs)
narcotic analgesics: in particular patients who are naive to narcotics |
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Term
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Definition
definitive diagnosis can only be made with biopsy or at autopsy
clinical diagnosis of probable AD
in general criteria include:
insidious onset of memory decline
decline in at least one other area of cognition (abstraction, calculation, judgment)
preserved level of consciousness (people who are delirious are not conscious of what is going on)
exclusion of other possible causes of symptoms |
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Term
| mental state evaluation (MMSE) categories of mild moderate and severe AD |
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Definition
< 24 = cognitive impairment
17-23 = mild
10-16 = moderate
< 10 = severe
is not meant to be a diagnostic tool |
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Term
| evaluation of functional status: ADLs and IADLs |
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Definition
ADLs: toileting, grooming, dressing, transferring, eating
IADLs: money management, medication management, using telephone, shopping |
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Term
| MOA of acethylcholinesterase inhibitors |
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Definition
drugs used to treat Alzheimer's disease act by inhibiting acetylcholinesterase activity
these drugs block the esterase-mediated metabolism of acetylcholine to choline and acetate.
this results in:
increased acetylcholine in the synaptic cleft
increased availability of acetylcholine for postsynaptic and presynaptic nicotinic (and muscarinic) acetylcholine receptors |
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Term
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Definition
5 mg QD to start
may increase to 10 mg QD after 4-6 weeks
donepezile is very tolerable AND THE STARTING DOSE IS A CLINICALLY EFFECTIVE DOSE
5 mg is an effective dose to improve cognition
all other drugs for AD have to be titrated up to the effective dose |
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Term
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Definition
VERY WELL TOLERATED
nausea
diarrhea
vomiting
no significant interactiosn with digoxin, theophylline, or warfarin
metabolized by CYP450 2D6 and 3A4
anticholinergics can negate effects (TCAs, detrol, antihistamines should not be used with donepezil!!)
warning in patients with:
COPD/asthma - Ach constricts the bronchioles and increases mucus production, also anticholinergics are used to treat it
PUD - Ach stimulates gastric acid production and AD drugs can increase gastric acid production
sick-sinus syndrome - bradycardia; Ach can slow the heart rate, these drugs can caused slowed HR. |
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Term
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Definition
starting dose at 1.5 mg BID
increase to 3 mg BID after at least 2-4 weeks, then to 4.5 mg BID then 6 mg BID
also available in patch form dosed at 4.6 mg/24hours and 9.5 mg/24hours applied once daily |
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Term
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Definition
nausea
diarrhea
anorexia
not appreciably metabolized in the liver, therefore low risk of drug interactions
anticholinergics can negate effects
must also be used with caution in COPD/asthma, PUD, sick-sinus/bradycardia |
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Term
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Definition
starting dose of 4 mg BID (IR) or 8 mg QD (ER)
can increase to 8 mg BID (IR) or 16 mg QD (ER) after 4 weeks then to 12 mg BID (IR) or 24 mg QD (ER)
16 MG QD IS THE CLINICALLY EFFECTIVE DOSE |
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Term
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Definition
nausea
vomiting
diarrhea
anorexia
metabolized by 2D6 and 3A4 in the liver
avoid anticholinergics
similar cautions in COPD, PUD, SSS |
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Term
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Definition
moderate affinity, noncompetitive NMDA receptor antagonist
does not impair physiologic function of NMDA receptor
can be used in combination with cholinesterase inhibitors
only approved for MODERATE TO SEVERE DISEASE
AChE inhibitors are approved for MILD TO MODERATE DISEASE (donepezil is also for SEVERE DISEASE) |
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Term
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Definition
usual starting dose is 5 mg daily
increase at weekly intervals to 5 mg BID, then 10 mg AM and 5 mg PM, then 10 mg BID |
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Term
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Definition
not largely metabolized, majority of drug excreted unchanged in urine
minimal inhibition of CYP450 enzymes
dosage reductions should be considered in patients with significant renal impairment
usually well tolerated; most common ADRs include: dizziness, headache, constipation, confusion, agitation, fatigue/somnolence |
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Term
| effects of gingko biloba on AD |
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Definition
contains flavenoids and terpionids that may have anti-oxidative and anti-inflammatory effects/specific extracts
mixed results but some studies suggest cognitive enhancing effects similar to AChE inhibitors
dose of 180 mg/day has shown positive results in one study and 120 mg/day showed no effect in another study
RISK OF BLEEDING (caution in patients taking aspirin, plavix, warfarin) |
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Term
| use of antipsychotics in AD |
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Definition
mildly effective for hallucinations and other positive symptoms related to AD
positive studies with risperidone, olanzapine, and quetiapine
INCREASED RISK OF STROKE/DEATH!!!
OBRA regulations: inappropriate for unsociability, wandering, uncooperativeness, poor self-care |
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Term
| use of benzodiazepines in AD |
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Definition
may be appropriate for anxiety and sleeping disorders
sedation, ataxia, falls, anterograde amnesia
should try to avoid benzodiazepines, but can be used at low doses for short periods of time |
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