1. What is delirium?
    • an acute or subacute change in cognition and attention or confusion; abnormal mental state
  2. What is mild cognitive impairment?
    • a transitional state b/w the cognition of normal aging and mild dementia without functional impairment
    • Not a dementia
  3. 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
  4. When can dementia not be diagnosed?
    when delirium is present
  5. What are the modifiable risk factors for delirium?
    • hearing or vision impairment
    • immobilization
    • meds
    • concurrent illness (infection, dehydration)
    • electrolyte abnormalities
    • surgery
    • environment (ICU, noise, people)
    • pain
    • emotional distress
    • sleep deprivation
    • acute neurological disorder (stroke)
  6. What are the non-modifiable risk factors for delirium?
    • dementia or cognitive impairment
    • age >65yo
    • comorbidities
    • male gender
    • renal or hepatic disease
    • hx of delirium
    • hx of CVA/neurological disease
    • hx of falls or gait disorder
  7. 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
  8. When do we use meds to tx delirium?
    when symptoms compromise safety or interfere with medical care
  9. What drugs are used to treat delirium?
    • neuroleptics (lowest dose for shortest duration)
    • e.g. Haldol <3mg/d
  10. What is the first sx of Alzheimer's dementia (AD)?
    memory loss
  11. What ist he first sx of frontotemporal dementia?
    • apathy
    • poor judgement/insight/speech/language
    • hyperorality
  12. What is the first sx of dementia of Lewy Bodies?
    • visual hallucinations
    • REM sleep disorder
    • delirium
    • Capgras' syndrome
    • parkinsonism
  13. What is the first sx of vascular dementia?
    • often, but not always, sudden
    • variable
    • apathy
    • falls
    • focal weakness
  14. What effect does Alzheimer's dementia (AD) have on mental status?
    episodic memory loss
  15. What effect does frontotemporal dementia have on mental satus?
    • frontal/executive
    • language
    • spares drawing
  16. What effect does dementia of the Lewy Bodies have on mental status?
    • drawing and frontal/executive
    • spares memory
    • delirium prone
  17. What effect does vascular dementia have on mental status?
    • frontal/executive
    • cognitive slowing
    • can spare memory
  18. What effect does Alzheimer's dementia (AD) have on neuropsychiatry?
    initially normal
  19. What effect does frontotemporal dementia have on neuropsychiatry?
    • apathy
    • disinhibition
    • hyperorality
    • euphoria
    • depression
  20. What effect does dementia of the Lewy Bodies have on neuropsychiatry?
    • visual hallucinations
    • depression
    • sleep disorder
    • delusions
  21. What effect does vascular dementia have on neuropsychiatry?
    • apathy
    • delusions
    • anxiety
  22. What effect does Alzheimer's dementia (AD) have on neurology?
    initally normal
  23. What effect does frontotemporal dementia have on neurology?
    • d/t PSP/CBD overlap
    • vertical gaze palsy
    • axial rigidity
    • dystonia
    • alien hand
  24. What effect does dementia of the Lewy Bodies have on neurology?
  25. What effect does vascular dementia have on neurology?
    • usually motor slowing
    • spasticity
    • can be normal
  26. 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
  27. 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
  28. What is the average survival for AD?
    8-10 years after onset of symptoms (up to 20)
  29. What problems does AD predispose pts to?
    • sepsis
    • pneumonia
    • choking
  30. 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
  31. What pt factors is the MMSE score subject to?
    • cognitive level
    • ability to see
    • ability to hear
  32. 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)
  33. What is the MMSE?
    • 19 items
    • 30pts
    • low score means high impairment
  34. What is the ADAS-cog?
    • 11 items
    • 70pts
    • high score means high impairment
  35. What is the mini-cog?
    • 2 items
    • 5pts
    • high score means high impairment
  36. When should you expect to see benefit from tx of AD?
    3-6 mos
  37. What classifies benefit from tx in AD?
    • < 2pt decline on MMSE
    • 4pt increase on ADAS-cog
  38. 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
  39. 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
  40. What meds can increase sx of AD?
    • anticholinergics
    • BZD
    • sleep aids
    • APs
    • narcotic analgesics
    • muscle relaxants
    • ADs
    • antiHTN
    • antiemetics
    • urinary antispasmodics
    • corticosteroids
    • hypoglycemic agents
  41. What cholinesterase inhibitors (CI) are used for AD?
    • tacrine (Cognex)
    • donepezil (Aricept)
    • rivastigmine (Exelon)
    • galantamine (Razadyne)
  42. Which CI is approved for all 3 forms of AD (mild, moderate, and severe)?
    donepezil (Aricept)
  43. What are the SE of CI?
    • NVD (may improve after a few wks)
    • dizziness
    • urinary incontinence (no help for this)
    • bradycardia/syncope
    • salivation
    • sweating
  44. What conditions should be watched closely when treating AD with CI?
    • bradycardia
    • sick sinus syndrome
    • supraventricular cardiac conduction abnormalities
    • PUD
    • bladder obstruction
  45. Which CI has the easiest dosing schedule?
    donepezil (Aricept)
  46. What should be done to minimize SE from CI?
    • titrate slowly
    • take with food
  47. What should be done if >7 doses of CI are missed?
    retitrate the drug
  48. How long must you be on donepezil (Aricept) 10mg before titrating to 23mg?
    at least 3mos
  49. What added MOA does rivastigmine (Exelon) have that the other CIs don't?
    inhibits butyrylcholinesterase as well as ACh-ase
  50. Which CI has the most GI SE?
    rivastigmine (Exelon) - titrate over 4-6 wks
  51. What added SE does rivastigmine (Exelon) have that the other CIs don't?
    dose-dependent wt loss
  52. Which CI has a patch formulation?
    rivastigmine (Exelon)
  53. 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
  54. What N-Methyl-d-Aspartic acid (NMDA) antagonists are used to tx AD?
    memantine (Namenda)
  55. What is the MOA of memantine (Namenda)?
    blocks glutamatergic neurotransmission by non-competetively blocking NMDA receptors
  56. What levels of AD is memantine (Namenda) approved for?
    moderate to severe
  57. Which drugs are approved to treat severe AD?
    • donepezil (Aricept)
    • memantine (Namenda)
  58. What may be as effective as adding memantine (Namenda) to donepezil (Aricept) 10mg tx for AD?
    donepezil (Aricept) 23mg
  59. What are the SE of memantine (Namenda)?
    • constipation
    • confusion
    • dizziness
    • HA
    • hallucinations
    • HTN
    • cough
  60. 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)
  61. Which Alzheimer's drug is in the form of an oral disintegrating tablet?
    donepezil (Aricept)
  62. What added SE does donepezil (Aricept) have that other CIs don't?
    • musculoskeletal SE
    • insomnia
  63. When should the pt be evaluated for SE when being tx for AD?
    after 2-4 wks
  64. When should the pt be evaluated for effectiveness when being treated for AD?
    q 6 mo
  65. What is the treatment for mild cognitive impairment?
    none are approved yet
  66. What is typical for vascular dementia pts to have in their med hx?
    • stroke
    • TIA
    • CVD
  67. What is the tx for vascular dementia?
    • focused on underlying cause (HTN, atherosclerosis, DM)
    • CIs are being studied (off-label)
    • memantine (Namenda) (off-label)
  68. What is a major differentiating sx of Lewy Body dementia?
    fluctuating cognitive fx (good and bad days)
  69. What is the onset of vascular dementia?
    • abrupt onset
    • stepwise progression
  70. What is the onset of Lewy Body dementia?
    • insidious onset
    • rapid progression
  71. What is less common in Lewy Body dementia?
    neurofibrillary tangles
  72. What are the tx of Lewy Body dementia?
    • rivastigmine (Exelon) - best evidence and safety
    • donepezil (Aricept) - off-label
    • levodopa/carbidopa (Sinemet) may be used
  73. Which dementia is characterized by moderate progression?
    frontotemporal dementia
  74. What are the tx for frontotemporal dementia?
    • SSRIs
    • AAPs
    • VPA
    • CBZ
  75. How is Parkinson's disease associated with dementia?
    cognitive impairment in late stages
  76. What are the tx for dementia sx of Parkinson's?
    • SSRIs
    • donepezil (Aricept)
    • rivastigmine (Exelon) - best safety and efficacy, but still only modest benefit
    • clonazepam for REM sleep disturbance
  77. 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
  78. What is the effect of estrogen on dementia?
    • associated with development of dementia and mild cognitive impairment
    • may increase sx
  79. Which drugs have studies that show a possible protective effect against dementia?
    • NSAIDs
    • HMG-CoA reductase inhibitors
  80. What is first line tx for behavioral sx associated with dementia?
    nonpharmacologic tx - identify the triggers and adapt the environment
  81. Which are the most common behavioral sx associated with dementia?
    • psychotic sx
    • inappropriate or disruptive behavior
  82. 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
  83. Which is the only drug which shows significant improvement in dementia-related psychosis?
    risperidone (Risperdal)
  84. Which drugs show improvement for neuropsychiatric sx of dementia?
    • risperidone (Risperdal)
    • aripiprazole (Abilify)
  85. What are the doses of FGAs used to tx psychosis of dementia?
    haloperidol (Haldol) 0.25mg/d
  86. 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
  87. 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
  88. What are the SE of APs in elderly pts with dementia?
    • sedation
    • OH
    • falls
  89. What tx are in development for dementia/Alzheimer's?
    • vaccines targeting B-amyloid peptide
    • monoclonal antibodies for passive
    • amyloid modulators
    • immunization:
    • bapineuzumab - phase III trials
    • solanezumab
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