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Dementia.2

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Dementia.2

  1. 1. Dementia Arden L Aylor, MD Geriatrics Texas Tech University
  2. 2. Goals & Objectives <ul><li>Statistics </li></ul><ul><li>Clinical Features </li></ul><ul><li>Diagnostic Criteria </li></ul><ul><li>Assessment Methods </li></ul><ul><li>Treatment Methods </li></ul>
  3. 3. Normal vs. Abnormal Aging <ul><li>>40 year-old: Age Associated Memory Impairment </li></ul><ul><li>Decline in Hepatic & Renal function </li></ul><ul><li>Vision changes </li></ul><ul><li>Hearing changes </li></ul>
  4. 4. Dementia <ul><li>Definition: The loss of cognitive and intellectual function, without impairment of perception or consciousness </li></ul><ul><li>Characterized by disorientation, impaired memory, judgment, intellect and labile affect </li></ul>
  5. 5. Did you Know… <ul><li>Five major types of Dementia </li></ul><ul><ul><li>Alzheimer’s: 60-70% </li></ul></ul><ul><ul><li>Cerebrovascular: 15-25% </li></ul></ul><ul><ul><li>Lewybody: 5-8% </li></ul></ul><ul><ul><li>Frontotemporal: 3-5% </li></ul></ul><ul><ul><li>Parkinson's with Dementia: 1-3% </li></ul></ul><ul><li>Estimated by 2040, 120 million </li></ul><ul><ul><ul><ul><ul><li> Arch Neuro, 2005 </li></ul></ul></ul></ul></ul>
  6. 6. Did you Know… <ul><li>Prevalence: 6-8% 60 yrs and doubles every 5 years </li></ul><ul><li>80 yrs: 47-50% population suffer from some form of dementia </li></ul><ul><li>www.aoa.dhhs.gov </li></ul>
  7. 7. Did you Know… <ul><li>2006 - total cost world wide exceeded $220 billion </li></ul><ul><ul><li>acute care </li></ul></ul><ul><ul><li>long-term care </li></ul></ul><ul><ul><li>home health care </li></ul></ul><ul><ul><li>lost productivity for caregivers </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><li>www.aoa.dhhs.gov </li></ul></ul>
  8. 8. Genetics <ul><li>The two major risk factors for dementia </li></ul><ul><ul><li>age </li></ul></ul><ul><ul><li>family history </li></ul></ul><ul><li>Alzheimer’s: 50% penetrance in first degree relatives by age 80 </li></ul>
  9. 9. Genetics <ul><li>Alzheimer’s (AD): before age 60 </li></ul><ul><ul><li>genetic mutations on chromosomes 1, 14, 21 </li></ul></ul><ul><li>Alzheimer’s (AD): after age 60 </li></ul><ul><ul><li>apolipoprotein E gene (APOE) on chromosome 19 </li></ul></ul>
  10. 10. Genetics <ul><li>APOE* 4/4 allele 6x increase risk in ( AD) </li></ul><ul><li>APOE* 2 appears to be protective </li></ul><ul><li>Other risk factors: </li></ul><ul><ul><li>head injury, education level, estrogen replacement after menopause, long-term NSAID’s </li></ul></ul>
  11. 11. Clinical Features <ul><li>Memory Impairment </li></ul><ul><li>Early Dementia: </li></ul><ul><ul><li>difficulty learning and retaining new information </li></ul></ul><ul><li>Late Dementia: </li></ul><ul><ul><li>inability to access distant memories, impaired judgment and executive function </li></ul></ul>
  12. 12. Clinical Features <ul><li>Dementia has a profound effect on the patient’s daily life: </li></ul><ul><ul><li>ADL’S (eating, bathing, grooming) </li></ul></ul><ul><ul><li>planning meals </li></ul></ul><ul><ul><li>managing finances </li></ul></ul><ul><ul><li>medications </li></ul></ul><ul><ul><li>communication </li></ul></ul><ul><ul><li>driving </li></ul></ul>
  13. 13. Clinical Features <ul><li>Early behavior and mood changes are common: </li></ul><ul><ul><li>personality alterations </li></ul></ul><ul><ul><li>irritability </li></ul></ul><ul><ul><li>anxiety </li></ul></ul><ul><ul><li>depression </li></ul></ul><ul><li>Late findings: Delusions, hallucinations, aggression and wandering </li></ul>
  14. 14. Clinical Features <ul><li>Dementia and depression often overlap </li></ul><ul><li>Depressed patients usually exhibit intact language and motor skills </li></ul><ul><li>55% over 65 yrs with mild cognitive impairment + depression, progress to moderate to severe dementia within 5 yrs </li></ul><ul><ul><ul><ul><ul><li>Arch Neuro, 2005 </li></ul></ul></ul></ul></ul>
  15. 15. Clinical Features <ul><li>Dementia & Agitation </li></ul><ul><ul><li>undiagnosed medical problem </li></ul></ul><ul><ul><li>pain </li></ul></ul><ul><ul><li>depression/ anxiety </li></ul></ul><ul><ul><li>delirium </li></ul></ul><ul><ul><li>environmental changes </li></ul></ul>
  16. 16. Six Diagnostic Criteria for Dementia <ul><li>1. Multiple cognitive deficits </li></ul><ul><ul><li>a. Memory impairment </li></ul></ul><ul><ul><li>b. One or more of the following: </li></ul></ul><ul><ul><ul><li>aphasia </li></ul></ul></ul><ul><ul><ul><li>apraxia </li></ul></ul></ul><ul><ul><ul><li>agnosia </li></ul></ul></ul><ul><ul><ul><li>disturbance in executive function </li></ul></ul></ul><ul><ul><ul><ul><li>Core Geri, 2005 </li></ul></ul></ul></ul>
  17. 17. Six Diagnostic Criteria for Dementia <ul><li>2. Cognitive deficits in 1a and 1b causing an impairment in social or occupational function which represents a significant decline from a previous level </li></ul><ul><li>3. Course is characterized by gradual onset and continued cognitive decline </li></ul>
  18. 18. Six Diagnostic Criteria for Dementia <ul><li>4. Cognitive deficits in 1a and 1b are not due to any of the following: </li></ul><ul><ul><ul><li>central nervous system condition causing progressive deficits in memory or cognition </li></ul></ul></ul><ul><ul><ul><li>systemic condition </li></ul></ul></ul><ul><ul><ul><li>substance-induced condition </li></ul></ul></ul>
  19. 19. Six Diagnostic Criteria for Dementia <ul><li>5. Deficits do not occur exclusively during the course of a delirium </li></ul><ul><li>6. Disturbance is not better accounted for by another Axis I disorder (major depression, schizophrenia ) </li></ul>
  20. 20. Mild Dementia <ul><li>Disorientation for dates </li></ul><ul><li>Naming difficulties (anomia) </li></ul><ul><li>Recent recall problems </li></ul><ul><li>Difficulty copying figures </li></ul><ul><li>Decreased insight </li></ul><ul><li>Social withdrawal </li></ul><ul><li>Irritability, mood changes </li></ul><ul><li>Problems managing finances </li></ul>
  21. 21. Moderate Dementia <ul><li>Disoriented to date and place </li></ul><ul><li>Comprehension difficulties </li></ul><ul><li>Impaired new learning </li></ul><ul><li>Getting lost in familiar areas </li></ul><ul><li>Impaired calculating skills </li></ul><ul><li>Delusions, agitation, aggression </li></ul><ul><li>Stop cooking, shopping, banking </li></ul><ul><li>Restless, anxious, depressed </li></ul><ul><li>Problems with dressing, grooming </li></ul>
  22. 22. Severe Dementia <ul><li>Unintelligible speech </li></ul><ul><li>Remote memory gone </li></ul><ul><li>Inability to copy or write </li></ul><ul><li>Loss of self care </li></ul><ul><li>Incontinent </li></ul>
  23. 23. Clinical Features <ul><li>Alzheimer’s Dementia </li></ul><ul><ul><li>Age: 70-75 </li></ul></ul><ul><ul><li>Cognition: Memory Impairment </li></ul></ul><ul><ul><li>Behavioral: Apathy, Depression </li></ul></ul><ul><ul><li>Neurological: Intact </li></ul></ul><ul><ul><li>Prognosis: Death 8-10 years </li></ul></ul>
  24. 24. Clinical Features <ul><li>Cerebrovascular Dementia </li></ul><ul><ul><li>Age: 70 </li></ul></ul><ul><ul><li>Cognition: Language, Memory, Executive Function Impairment </li></ul></ul><ul><ul><li>Behavioral: Agitation, Hallucinations, Depression </li></ul></ul><ul><ul><li>Neurological: Frontal Release Signs, </li></ul></ul><ul><ul><li>(+) Brain Imaging Studies </li></ul></ul><ul><ul><li>Prognosis: Death 5-8 years </li></ul></ul>
  25. 25. Clinical Features <ul><li>Lewybody Dementia </li></ul><ul><ul><li>Age: 65 </li></ul></ul><ul><ul><li>Cognition: Memory, Executive Function & Orientation Impairment </li></ul></ul><ul><ul><li>Behavioral: Visual Hallucinations, Depression </li></ul></ul><ul><ul><li>Neurological: Parkinsonism </li></ul></ul><ul><ul><li>Prognosis: Death 6-8 years </li></ul></ul>
  26. 26. Clinical Features <ul><li>Frontotemporal Dementia </li></ul><ul><ul><li>Age: 65 </li></ul></ul><ul><ul><li>Cognition: Executive Function Impairment </li></ul></ul><ul><ul><li>Behavioral: Social Inhibition </li></ul></ul><ul><ul><li>Neurological: Intact </li></ul></ul><ul><ul><li>Prognosis: Death 6-8 years </li></ul></ul>
  27. 27. Clinical Features <ul><li>Parkinson’s with Dementia </li></ul><ul><ul><li>Age: 70 </li></ul></ul><ul><ul><li>Cognition: Memory, Executive Function, Language, Orientation Impairment </li></ul></ul><ul><ul><li>Behavioral: Depression, Hallucinations </li></ul></ul><ul><ul><li>Neurological: Parkinson’s Disease </li></ul></ul><ul><ul><li>Prognosis: Death <5 years </li></ul></ul>
  28. 28. Assessment Methods <ul><li>Informant interview and office evaluation are the most important diagnostic tools </li></ul><ul><li>Functional Status: MMSE , Functional Activities Questionnaire (FAQ), Geriatric Depression Screening, Clock Drawing Test </li></ul><ul><li>Laboratory: CBC, CMP, TSH, Serology for Syphilis, Vitamin B12, HIV </li></ul><ul><ul><li>Core Geri, 2005 </li></ul></ul>
  29. 29. Assessment Methods <ul><li>Brain Imaging (CT, MRI, PET) </li></ul><ul><ul><li>atrophy </li></ul></ul><ul><ul><li>space-occupying lesions </li></ul></ul><ul><ul><li>vascular disease </li></ul></ul><ul><ul><li>whiter matter disease </li></ul></ul>
  30. 31. Assessment Methods <ul><li>Imaging Studies </li></ul><ul><ul><li>Order if-- </li></ul></ul><ul><ul><ul><li>onset before 60 yrs </li></ul></ul></ul><ul><ul><ul><li>post-acute illness less that 18 months </li></ul></ul></ul><ul><ul><ul><li>neurologic finding are asymmetric </li></ul></ul></ul><ul><ul><ul><li>gait disturbance </li></ul></ul></ul><ul><ul><ul><li>incontinence unexplained </li></ul></ul></ul>
  31. 32. Treatment and Management <ul><li>Goal: Enhance quality of life, maximize function, improve cognition, mood and behavior </li></ul><ul><ul><li>non-pharmacological </li></ul></ul><ul><ul><li>pharmacological </li></ul></ul>
  32. 33. Nonpharmacologic <ul><li>Cognitive Enhancement </li></ul><ul><ul><li>reality orientation and memory training </li></ul></ul><ul><li>Individual and Group Therapy </li></ul><ul><ul><li>emotional orientated psychotherapy </li></ul></ul><ul><ul><li>stimulation orientated therapy </li></ul></ul><ul><ul><li>art and exercise </li></ul></ul>
  33. 34. Other Nonpharmacologic <ul><li>Communication with family and caregiver </li></ul><ul><li>Medical and legal Advance Directives </li></ul><ul><li>Environmental Modifications </li></ul><ul><ul><li>moderate stimulation only </li></ul></ul><ul><ul><li>memory measures </li></ul></ul><ul><ul><ul><li>clocks, calendars, to-do lists </li></ul></ul></ul><ul><ul><ul><li>name tags, alert bracelets </li></ul></ul></ul>
  34. 35. Pharmacologic <ul><li>Individualized treatment </li></ul><ul><li>Monitor renal clearance and hepatic metabolism </li></ul><ul><li>Anticholinergic medications worsen cognitive impairment </li></ul><ul><li>“ Start low and go slow” </li></ul><ul><li>Avoid starting multiple medications </li></ul>
  35. 36. Pharmacologic <ul><li>Alzheimer’s Dementia </li></ul><ul><ul><li>Cholinesterase Inhibitors </li></ul></ul><ul><ul><ul><li>Donepezil (Aricept) </li></ul></ul></ul><ul><ul><ul><li>Galantamine (Razadyne) </li></ul></ul></ul><ul><ul><ul><li>Rivastigmine (Exelon) </li></ul></ul></ul><ul><ul><li>Memantine (Namenda) </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul>
  36. 37. Pharmacologic <ul><li>Cerebrovascular Dementia </li></ul><ul><ul><li>Cholinesterase Inhibitors </li></ul></ul><ul><ul><li>Control lipids </li></ul></ul><ul><ul><li>Stoke prevention </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul><ul><ul><li>Memantine </li></ul></ul><ul><ul><li>Anticonvulsants </li></ul></ul><ul><ul><li>Antipsychotics </li></ul></ul>
  37. 38. Pharmacologic <ul><li>Frontotemporal Dementia </li></ul><ul><ul><li>No Cholinesterase Inhibitors </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul><ul><ul><li>Memantine </li></ul></ul><ul><ul><li>Anticonvulsants </li></ul></ul><ul><ul><li>Antipsychotics </li></ul></ul>
  38. 39. Pharmacologic <ul><li>Lewybody Dementia (Pick’s disease) </li></ul><ul><ul><li>Cholinesterase Inhibitors </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul><ul><ul><li>Memantine </li></ul></ul><ul><ul><li>Levodopa/ Carbidopa </li></ul></ul><ul><ul><li>Antipsychotic </li></ul></ul>
  39. 40. Pharmacologic <ul><li>Parkinson’s Disease with Dementia </li></ul><ul><ul><li>Treat the Parkinson’s disease </li></ul></ul><ul><ul><li>No Cholinesterase Inhibitors </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul><ul><ul><li>Memantine </li></ul></ul><ul><ul><li>Antipsychotic </li></ul></ul>
  40. 41. Cholinesterase Inhibitors <ul><li>Donepezil (Aricept) </li></ul><ul><ul><li>Precautions : Nausea, vomiting, diarrhea, </li></ul></ul><ul><ul><li>GI bleed, sick sinus syndrome, seizures </li></ul></ul><ul><ul><li>Interactions : CYP2D6 (flecainide, metopropol, codeine) , used with NSAID 3-4x risk for GI bleed </li></ul></ul>
  41. 42. Cholinesterase Inhibitors <ul><li>Galantamine (Razadyne) </li></ul><ul><ul><li>Precautions : AV block, seizures, bladder obstruction, renal and hepatic, GI bleed, </li></ul></ul><ul><ul><li>GI upset </li></ul></ul><ul><ul><li>Interactions : CYP3A4 (cholinergic agonist -bethanechol, ketoconazole, cimetidine, erythromycin) </li></ul></ul>
  42. 43. Cholinesterase Inhibitors <ul><li>Rivastigmine (new q 24 Exelon Patch) </li></ul><ul><ul><li>Precautions : Nausea, vomiting, anoxia, </li></ul></ul><ul><ul><li>GI bleed, sick sinus syndrome, seizures </li></ul></ul><ul><ul><li>Interactions : CYP2D6 and CYP3A4, potentates muscle relaxants, used with NSAID 3-4x risk for GI bleed </li></ul></ul>
  43. 44. NMDA [glutamate] antagonist <ul><li>Memantine (Namenda) </li></ul><ul><ul><li>Precautions : Dizziness, headache, alkalinized urine (ATN, UTI) seizures, GI upset </li></ul></ul><ul><ul><li>Interactions : Other NMDA antagonists (amantadine, dextromethorphan), decreased by renally-excreted drugs (HCTZ) </li></ul></ul>
  44. 45. Mild to Moderate Dementia <ul><li>Cholinesterase Inhibitors slow cognitive decline </li></ul><ul><li>Meta Analysis - Delayed nursing home placement by 1.2 years </li></ul><ul><ul><ul><li>NNT 9.6 </li></ul></ul></ul><ul><ul><ul><ul><ul><li>www.aoa.dhhs.gov </li></ul></ul></ul></ul></ul>
  45. 46. Moderate to Severe <ul><li>Memantine: 1-3 year delay in progression of symptoms </li></ul><ul><ul><li>NNT 16.2 </li></ul></ul><ul><li>Memantine + Cholinesterase inhibitor </li></ul><ul><ul><li>No definitive data </li></ul></ul><ul><ul><ul><li>early combination may decrease progression from mild to severe dementia by 4-5 years Ann Intern Med , 2004 </li></ul></ul></ul>
  46. 47. Research: What’s New <ul><ul><li>Tramiprostate (Alzhemed) </li></ul></ul><ul><ul><ul><li>mechanism: Inhibits GAG & A β protein fibrillization </li></ul></ul></ul><ul><ul><ul><li>reduces amyloid formation and accumulation </li></ul></ul></ul><ul><ul><li>Tarenflurbil (Flurizan) </li></ul></ul><ul><ul><ul><li>r-flurbiprofen </li></ul></ul></ul><ul><ul><ul><li>mechanism: Selective Amyloid-Lowering Agent (SALA) </li></ul></ul></ul><ul><ul><ul><li>inhibits A β 42 amyloid plaques cascade </li></ul></ul></ul><ul><ul><li>Alzheimer’s Vaccine </li></ul></ul>
  47. 48. Research <ul><li>Other studies </li></ul><ul><ul><li>estrogen </li></ul></ul><ul><ul><li>NSAIDS </li></ul></ul><ul><ul><li>vitamin E (increase cardiac events) </li></ul></ul><ul><ul><li>selective monoamine oxidase-B inhibitor </li></ul></ul><ul><ul><li>ginko biloba </li></ul></ul><ul><ul><li>prophylaxis cholinesterase treatment </li></ul></ul><ul><ul><ul><ul><ul><li>J Gerontol a Bio Sci Med , 2004 </li></ul></ul></ul></ul></ul>
  48. 49. Antidepressants <ul><li>Guidelines (American & UK Geriatric Society) </li></ul><ul><ul><li>treating all patients with dementia and signs of depression/ anxiety with an SSRI or SNRI </li></ul></ul>
  49. 50. All SSRI are not Equal <ul><li>Paroxetine (Paxil): Drug interaction, anti-cholinergic </li></ul><ul><li>Fluoxetine (Prozac): Long half life, anorexia </li></ul><ul><li>Sertraline (Zoloft): Good, sleepy </li></ul><ul><li>Citalopram (Celexa): Good, mild hypotension </li></ul><ul><li>Escitlopram (Lexapro): Good, mild hypotension </li></ul>
  50. 51. “ Sundowning” <ul><li>Mild Dementia </li></ul><ul><ul><li>late afternoon or evening confusion </li></ul></ul><ul><li>Severe Dementia </li></ul><ul><ul><li>agitation, irritability restlessness </li></ul></ul>
  51. 52. “ Sundowning” <ul><li>Etiology: </li></ul><ul><ul><li>lack of clues from light/ dark cycling </li></ul></ul><ul><ul><li>decrease sensory input </li></ul></ul><ul><ul><li>environmental changes </li></ul></ul><ul><ul><li>lack of a structure daily routine </li></ul></ul><ul><ul><li>change in caregivers </li></ul></ul>
  52. 53. “ Sundowning” <ul><li>Recommendations </li></ul><ul><ul><li>R/O occult medical problems </li></ul></ul><ul><ul><ul><li>infection </li></ul></ul></ul><ul><ul><ul><li>medication changes </li></ul></ul></ul><ul><ul><li>avoid dramatic changes in living environment </li></ul></ul><ul><ul><li>encourage familiar home surroundings </li></ul></ul>
  53. 54. Key Points <ul><li>Interviews & office evaluations are the most important diagnostic tools </li></ul><ul><li>Goal: Enhance quality of life, maximize function, improve cognition, mood and behavior </li></ul><ul><li>Not all SSRI’s are equal </li></ul><ul><li>Individualized treatment </li></ul><ul><ul><li>mild - moderate: cholinesterase inhibitors, </li></ul></ul><ul><ul><li>SSRI’s </li></ul></ul><ul><ul><li>moderate - severe: memantine, SSRI’s or combinations </li></ul></ul>
  54. 55. References <ul><li>Cobb, Duthie, Murphy; Geriatric Review Syllabus: A Core curriculum in Geriatrics, 5th ed, 2005, 117-129 </li></ul><ul><li>Peterson, Smith, Waring, Mild Cognitive Impairment, Arch Neurol ., 2005(3): 303-308 </li></ul><ul><li>Royall, Chaiodo, Polk, Subclinical Cognitive Impairment, J Gerontol a Bio Sci Med , 2004;55 (9):M541-M546 </li></ul><ul><li>Grifford, Holloway, Frankel, Improving adherence to dementia, A randomized Controlled Trial, Ann Intern Med , 2004;131(40):237-246 </li></ul><ul><li>Governmental Administration on Aging & Research www.aoa.dhhs.gov </li></ul><ul><li>Alzheimer Research Forum, www.alzhforum.org/drug </li></ul>
  55. 56. Assessment: PET <ul><ul><li>Alzheimer's Disease </li></ul></ul><ul><ul><ul><li>Parietal & Temporal deficits with intact neurology </li></ul></ul></ul><ul><ul><li>Frontotemporal </li></ul></ul><ul><ul><ul><li>Frontal & Temporal deficits </li></ul></ul></ul><ul><ul><li>Parkinson’s with dementia </li></ul></ul><ul><ul><ul><li>Parietal deficits </li></ul></ul></ul><ul><ul><li>Vascular dementia </li></ul></ul><ul><ul><ul><li>Focal, asymmetric </li></ul></ul></ul>

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