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Dementia.2 Dementia.2 Presentation Transcript

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