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GoT of dementia Tx
- alter disease progression
- treat s/s
- alleviate caregiver burden
- minimize ADRs
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Epidemiology of dementia
- incidence: 7/1000 (65-69y/o), doubles q5years, then 120/1000 (85-89y/o)
- prevalence: 8% in elderly
- cost: 1.5x more
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Etiology of dementia
- Alzheimer's disease
- vascular dementia
- frontotemporal lob
- dementia with Lewy bodies
- PD
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Treatable factors of dementia
- vitamin B12 deficiency
- hypothyrodism
- depression
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Drug-induced dementia
- polypharmacy
- anticholinergics
- antipsychotics
- sedative/hypnotics
- narcotics
- PHT
- CC
- NSAIDs
- digitalis
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DSM-IV-TR diagnostic criteria for dementia
- 1. memory impairment
- 2. >1 of the following: aphasia (language disturbance), apraxia (impaired motor despite intact motor function), agnosia (impaired recognition despite intact sensation), disturbed executive functioning (planning, organizing)
- 3. cognitive deficit impairs social or occupational function
- 4. gradual onset and progressive cognitive decline
- 5. no s/s during delirium
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Clinical features of dementia
- 1. ADLs: self-care vs. instrumental
- 2. behavior: agitation, apathy, anxiety, depression, irritability, delusions, hallucinations
- 3. cognition: memory, word finding, repetitiveness, executive function
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Diagnostic scores for dementia
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Pharmacotherapy options for dementia
- 1. cholinesterase inhibitors: donepezil (I= mild-severe), rivastigmine (I= mild-mod), galantamine (I=mild-mod)
- 2. NMDA R antagonist: memantine (I= mod-severe)
- 3. gingko biloba: questionable efficacy
- 4. estrogens: epidemiological data but disappointing trials
- 5. NSAIDs: epidemiological data but disappointing trials
- 6. vitamin E 1000IU BID: one study showed delayed AD progression
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Tx options for AD dementia
- all cholinesterase inhibitors are modestly efficacious with mild-mod
- memantine has small benefit on cognition, function, and behavior in mod-severe AD
- ChEI+memantine is rational esp. in mod-severe
- results of Tx of severe AD (MMSE<10m, GDS=6-7) is totally variable
- *switching from donepezil to rivastigmine patch= wait 5-7days
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What is vascular dementia (VaD)?
- due to cerebrovascular hemorrhage or ischemia
- etiology: HTN, DM, increased lipids, embolism
- Hachinski ischemic scale is used to differentiate VaD from AD (<4= AD, >7= VaD)
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Characteristics of vascular dementia
- abrupt onsetplateaus of stable function
- change in gait
- seizures
- patchy cognitive deficits
- urinary incontinence
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Tx options for VaD
Tx may be modestly beneficial
- efficacy for global function @24weeks
- 1. donepezil: NNT=11
- 2. galantamine: NNT=7
- 3. rivastigmine: insufficient evidence
- 4. memantine: NSS NNT=13
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Characteristics of dementia with Lewy bodies (DLB)
- fluctuating cognitive impairment
- recurrent visual hallucination
- Parkinsonism
- dementia occurs <1year after Parkinsonian s/s onset
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Tx optiond for DLB
- ChEIs provide benefit for cognition and behavior but increase the risk of Parkinsonism
- 1. rivastigmine: improved behavior with no change in Parkinsonism with mild-mod DLB
- 2. galantamine: improved behavior and global function with mild-mod DLB
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Tx options for PD dementia
- ChEIs= increase risk of Parkinsonian s/s
- 1. rivastigmine improves cognition nad global function but significantly more N/V/tremor
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Characteristics of frontotemporal dementia (FTD)
- 1. behavioral changes: verbal and social disinhibition, emotional blunting
- 2. language impairment: progressive aphasia
- 3. relative memory sparing
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Tx options for frontotemporal dementia (FTB)
- ChEIs are not effective for behavioral s/s
- 1. donepezil: worsen FTB behavior
- 2. rivastigmine: improve behavior but data from open-label study
- 3. galantamine: ND
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Duration of dementia Tx
ChEIs can slow cognitive decline over 4-5years
- if d/c, then taper x2weeks
- monitor upon d/s and consider reinstating withing 2-6weeks if breakthrough s/s (decrease in cognition/function, behavioral changes)
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CI and precautions of ChEIs
- epilepsy (dementia+ChEIs= lower seizure threshold)
- history of seizure/DI
- hepatic/renal disease
- significant bradycardia
- significant bronchospastic disease
- PUD
- obstructive urinary disease
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Management of ChEIs S/E
- d/c if disabling or dangerous
- decrease dose if minor s/e and can retry dose after 2-4weeks
- antiemetics may have anticholinergic effects
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CI and precautions of memantine
- seizure history
- cardiovascular disorder
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S/E of memantine
- 1. CNS (6%): dizziness, confusion, HA
- 2. GI: N/V (3%), constipation (5%)
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DI of memantine
urinary alkalizers (carbonic anhydrase inhibitors)= decrease memantine clearance
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Dementia Tx dosing regimen
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Behavioral and psychological S/S of dementia (BPSD)
personality change, depression, agitation, misidentification= common
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BPSD that are medication responsive
- anxiety
- restlessness
- sadness
- insomnia
- feeling withdrawn
- verbal/physical aggression
- delusions and hallucinations
- sexually inappropriate behavior
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BPSD that are unlikely to be medication-responsive
- wandering
- inappropriate dressing
- repetitivenss
- hiding/hoarding
- eating inedibles
- inappropriate isolation
- removal of restraints
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Progression of BPSD
- 1. MMSE 25: depression, apathy, withdrawal
- 2. MMSE 15: depression, delusions, agitation, wandering, insomnia
- 3. MMSE 5: agitation, insomnia
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Harms of antipsychotic Tx in dementia patients
- EPS
- impaired cognition
- increased hospitalizations
- death (HR= 1.54)
*avoid QTP in DLB due to increased Parkinsonian s/s)
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Alzheimer's Drug Therapy Initiative (ADTI)
- coverage only if:
- 1. MMSE 10-26
- 2. GDS 4-6
- 3. have ability or social support to properly take medication
- 4. no CI
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