What is delirium?
- an acute or subacute change in cognition and attention or confusion; abnormal mental state
- NOT A DISEASE
What is mild cognitive impairment?
- a transitional state b/w the cognition of normal aging and mild dementia without functional impairmentNot a dementia
What is dementia?
- acquired deterioration in cognition that impairs activities of daily living that results from various central neurodegenerative and ischemic processes
- may affect memory, language, visuospatial ability, calculation, judgement, and/or problem solving
- neuropsychiatric and social deficits may be present: depression, withdrawal, hallucinations, agitation, insomnia, and disinhibition
When can dementia not be diagnosed?
when delirium is present
What are the modifiable risk factors for delirium?
- hearing or vision impairment
- concurrent illness (infection, dehydration)
- electrolyte abnormalities
- environment (ICU, noise, people)
- emotional distress
- sleep deprivation
- acute neurological disorder (stroke)
What are the non-modifiable risk factors for delirium?
- dementia or cognitive impairment
- age >65yo
- male gender
- renal or hepatic disease
- hx of delirium
- hx of CVA/neurological disease
- hx of falls or gait disorder
What are the nonpharmacological tx for delirium?
- minimize sensory impairment
- reorient the pt - play cards or something to keep them thinking
- correct dehydration
- early mobilization
- avoid use of physical restraints and urinary catheters when possible
- environmental interventions:
- limit room and staff changes
- keep room quiet
- low level lighting at night
- minimize night-time interruptions
When do we use meds to tx delirium?
when symptoms compromise safety or interfere with medical care
What drugs are used to treat delirium?
- neuroleptics (lowest dose for shortest duration)
- e.g. Haldol <3mg/d
What is the first sx of Alzheimer's dementia (AD)?
What ist he first sx of frontotemporal dementia?
- poor judgement/insight/speech/language
What is the first sx of dementia of Lewy Bodies?
- visual hallucinations
- REM sleep disorder
- Capgras' syndrome
What is the first sx of vascular dementia?
- often, but not always, sudden
- focal weakness
What effect does Alzheimer's dementia (AD) have on mental status?
episodic memory loss
What effect does frontotemporal dementia have on mental satus?
- spares drawing
What effect does dementia of the Lewy Bodies have on mental status?
- drawing and frontal/executive
- spares memory
- delirium prone
What effect does vascular dementia have on mental status?
- cognitive slowing
- can spare memory
What effect does Alzheimer's dementia (AD) have on neuropsychiatry?
What effect does frontotemporal dementia have on neuropsychiatry?
What effect does dementia of the Lewy Bodies have on neuropsychiatry?
- visual hallucinations
- sleep disorder
What effect does vascular dementia have on neuropsychiatry?
What effect does Alzheimer's dementia (AD) have on neurology?
What effect does frontotemporal dementia have on neurology?
- d/t PSP/CBD overlap
- vertical gaze palsy
- axial rigidity
- alien hand
What effect does dementia of the Lewy Bodies have on neurology?
What effect does vascular dementia have on neurology?
- usually motor slowing
- can be normal
What are the risk factors for Alzheimer's dementia (AD)?
- family hx
- age >65 (affects 20-40% over 85yo)
- few years of formal education
- late-onset depression
- mutations on chromosomes 1, 14, 21
- Down Syndrome
- Apo E4 presense on chromosome 19
- vascular disease risk factors (diabetes increases risk x 3)
- head injury
- decreased brain reserve capacity
What is correlated with early onset AD?
- genetic mutations on chromosomes 1, 14, 21
- chromosome 1 produces presenilin 2
- chromosome 14 produces presenilin 1
- (these encode for proteins involved in amyloid precursor protein - APP)
- Chromosome 21 encodes for APP = production of B-amyloid protein
What is the average survival for AD?
8-10 years after onset of symptoms (up to 20)
What problems does AD predispose pts to?
What is a normal scale progression for untreated AD?
- increase in ADAS-COG:
- 4pts over 6 mos
- 7pts over 1 yr
- decline in MMSE:
- 2-4pts per yr
What pt factors is the MMSE score subject to?
- cognitive level
- ability to see
- ability to hear
What are the stages of the MMSE?
- 27-30 = mild cognitive impairment
- 18-16 = mild AD
- 10-17 = moderate AD (2-8y from sx onset)
- 0-9 = severe AD (6-12y from sx onset)
What is the MMSE?
- 19 items
- low score means high impairment
What is the ADAS-cog?
- 11 items
- high score means high impairment
What is the mini-cog?
- 2 items
- high score means high impairment
When should you expect to see benefit from tx of AD?
What classifies benefit from tx in AD?
- < 2pt decline on MMSE
- 4pt increase on ADAS-cog
What are the tx goals for Alzheimer's dementia (AD)?
- treat cognitive difficulties and preserve pt fx as long as possible
- tx psychiatric and behavioral consequences of disease
- When slowing cognitive decline is no longer a goal, d/c tx with cholinesterase inhibitors (CI) - taper off
What are the nonpharmacological tx for AD?
- educate pt and family on course of illness and prognosis, available tx, legal issues, end-of-life issues
- minimize environmental triggers and redirect pt attention (noise, background distraction, personal discomfort)
- use memory aids (lists, calendars, labels)
- short-term tasks - avoid complex tasks
- exercise helps with anxiety and agitation
What meds can increase sx of AD?
- sleep aids
- narcotic analgesics
- muscle relaxants
- urinary antispasmodics
- hypoglycemic agents
What cholinesterase inhibitors (CI) are used for AD?
- tacrine (Cognex)
- donepezil (Aricept)
- rivastigmine (Exelon)
- galantamine (Razadyne)
Which CI is approved for all 3 forms of AD (mild, moderate, and severe)?
What are the SE of CI?
- NVD (may improve after a few wks)
- urinary incontinence (no help for this)
What conditions should be watched closely when treating AD with CI?
- sick sinus syndrome
- supraventricular cardiac conduction abnormalities
- bladder obstruction
Which CI has the easiest dosing schedule?
What should be done to minimize SE from CI?
- titrate slowly
- take with food
What should be done if >7 doses of CI are missed?
retitrate the drug
How long must you be on donepezil (Aricept) 10mg before titrating to 23mg?
at least 3mos
What added MOA does rivastigmine (Exelon) have that the other CIs don't?
inhibits butyrylcholinesterase as well as ACh-ase
Which CI has the most GI SE?
rivastigmine (Exelon) - titrate over 4-6 wks
What added SE does rivastigmine (Exelon) have that the other CIs don't?
dose-dependent wt loss
Which CI has a patch formulation?
What added MOA does galantamine (Razadyne) have that the other CIs don't?
enhances the action of ACh on nicotinic receptors as well as reversible ACh-ase inhibition
What N-Methyl-d-Aspartic acid (NMDA) antagonists are used to tx AD?
What is the MOA of memantine (Namenda)?
blocks glutamatergic neurotransmission by non-competetively blocking NMDA receptors
What levels of AD is memantine (Namenda) approved for?
moderate to severe
Which drugs are approved to treat severe AD?
- donepezil (Aricept)
- memantine (Namenda)
What may be as effective as adding memantine (Namenda) to donepezil (Aricept) 10mg tx for AD?
donepezil (Aricept) 23mg
What are the SE of memantine (Namenda)?
What issues should be watched closel when instituting memantine (Namenda) tx in AD?
- severe renal impairment
- severe hepatic impairment
- dietary or medical changes that alkalinize the urine - decreases renal excretion of memantine (Namenda)
Which Alzheimer's drug is in the form of an oral disintegrating tablet?
What added SE does donepezil (Aricept) have that other CIs don't?
- musculoskeletal SE
When should the pt be evaluated for SE when being tx for AD?
after 2-4 wks
When should the pt be evaluated for effectiveness when being treated for AD?
q 6 mo
What is the treatment for mild cognitive impairment?
none are approved yet
What is typical for vascular dementia pts to have in their med hx?
What is the tx for vascular dementia?
- focused on underlying cause (HTN, atherosclerosis, DM)
- CIs are being studied (off-label)
- memantine (Namenda) (off-label)
What is a major differentiating sx of Lewy Body dementia?
fluctuating cognitive fx (good and bad days)
What is the onset of vascular dementia?
- abrupt onset
- stepwise progression
What is the onset of Lewy Body dementia?
- insidious onset
- rapid progression
What is less common in Lewy Body dementia?
What are the tx of Lewy Body dementia?
- rivastigmine (Exelon) - best evidence and safety
- donepezil (Aricept) - off-label
- levodopa/carbidopa (Sinemet) may be used
Which dementia is characterized by moderate progression?
What are the tx for frontotemporal dementia?
How is Parkinson's disease associated with dementia?
cognitive impairment in late stages
What are the tx for dementia sx of Parkinson's?
- donepezil (Aricept)
- rivastigmine (Exelon) - best safety and efficacy, but still only modest benefit
- clonazepam for REM sleep disturbance
What should not be used to tx dementia in Parkinson's?
- Olanzapine (Zyprexa) may exacerbate Parkinson's
- memantine (Namenda) may exacerbate psychiatric sx or cognition
What is the effect of estrogen on dementia?
- associated with development of dementia and mild cognitive impairment
- may increase sx
Which drugs have studies that show a possible protective effect against dementia?
- HMG-CoA reductase inhibitors
What is first line tx for behavioral sx associated with dementia?
nonpharmacologic tx - identify the triggers and adapt the environment
Which are the most common behavioral sx associated with dementia?
- psychotic sx
- inappropriate or disruptive behavior
When are pharmacologic tx indicated for behavioral sx associated with dementia?
- when sx are distressing to pt or caregiver
- interfere w/ functioning or delivery of care
- poses a danger to self or others
Which is the only drug which shows significant improvement in dementia-related psychosis?
Which drugs show improvement for neuropsychiatric sx of dementia?
- risperidone (Risperdal)
- aripiprazole (Abilify)
What are the doses of FGAs used to tx psychosis of dementia?
haloperidol (Haldol) 0.25mg/d
What are the doses of AAPs used to tx psychosis of dementia?
- risperidone (Risperdal) 0.5mg/d
- olanzapine (Zyprexa) 2.5mg/d
- quetiapine (Seroquel) 25mg/d
- aripiprazole (Abilify) 10mg/d
What are the doses of SSRIs used to tx anxiety and depression of dementia?
- citalopram (Celexa) 10mg/d
- escitalopram (Lexapro) 5mg/d
- sertraline (Zoloft) 25mg/d
What are the SE of APs in elderly pts with dementia?
What tx are in development for dementia/Alzheimer's?
- vaccines targeting B-amyloid peptide
- monoclonal antibodies for passive
- amyloid modulators
- bapineuzumab - phase III trials