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Dementia

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					Dementia
Prof AK Daif
      WHAT IS DEMENTIA?
• An acquired syndrome of decline in memory and other
  cognitive functions sufficient to affect daily life in an alert
  patient

• Progressive and disabling

• NOT an inherent aspect of aging

• Different from normal cognitive lapses




                                                                    2
      Dementias – classification
Based on site
DSM-IV DIAGNOSTIC CRITERIA FOR
             AD
• Development of cognitive deficits manifested by both
       • impaired memory
       • aphasia, apraxia, agnosia, disturbed executive function
• Significantly impaired social, occupational function
• Gradual onset, continuing decline
• Not due to CNS or other physical conditions        (e.g., PD,
  delirium)
• Not due to an Axis I disorder (e.g., schizophrenia)




                                                                   5
          NORMAL LAPSES
               vs
            DEMENTIA
• Forgetting a name        • Not recognizing family
                             member
• Leaving kettle on        • Forgetting to serve
                             meal just prepared
• Finding right word       • Substituting
                             inappropriate words
                           • Getting lost in own
• Forgetting date or day     neighborhood


                                                      6
                                Mild Cognitive
                                   Impairment
  “Mild Cognitive Impairment (MCI) is a state between normal
         cognition and dementia, characterized by deficits not
        explainable by age, educational background, or medical
                               illness.”
Kryscio RJ, Schmitt FA, et al. Risk factors for transitions from normal to mild cognitive impairment and dementia. Neurology
                                                          2006; 66: 828-32.



• MCI is common (5-25%)
• MCI carries an increased risk of dementia and of death
     – If the deficits exist primarily in memory and executive function, risk of
       progression to dementia is higher
            • 10-15% per yr rate of development of dementia and AD compared to 1-7% per yr
              for those without MCI



                                                                                                                        7
    DIFFERENTIAL DIAGNOSIS
         FOR DEMENTIA
•   Alzheimer’s disease
•   Vascular (multi-infarct) dementia
•   Dementia associated with Lewy bodies
•   Delirium
•   Depression
•   Other (alcohol, Parkinson's disease [PD], Pick’s
    disease, frontal lobe dementia, neurosyphilis)




                                                       8
           ASSESSMENT:
         HISTORY/PHYSICAL
• Ask both the patient & a     •   Neurologic status
  reliable informant           •   Functional Status
• Current condition            •   Mental Status
• Medical history              •   ie. Folstein, MiniCog,
• Current medications          •   Neuropsych testing
• Patterns of alcohol use or
  abuse
• Living arrangements




                                                            9
    Evaluation of Dementia
• Standard laboratory studies
   – Complete blood count
       • Anemia, infection
   – Comprehensive metabolic panel
       • Glucose, electrolytes, renal or hepatic failure
   – Thyroid function tests


• Studies done in suspect cases
   – Estimated sedimentation rate
   – Serology for syphilis, HIV, lyme disease
   – Screen for heavy metals



                                                           10
       ASSESSMENT: BRAIN IMAGING
• Use imaging when:
   –   Onset occurs at age < 65 years
   –   Symptoms have occurred for < 2 years
   –   Neurologic signs are asymmetric
   –   Clinical picture suggests normal-pressure hydrocephalus


• Consider:
   – Noncontrast computed topography head scan
   – Magnetic resonance imaging
   – Positron emission tomography




                                                                 11
      Evaluation of Dementia
• Radiologic/Neuro-Imaging studies
• Carotid dopplers
• CT Scan, MRI of Brain
    – Linear/volumetric measurement is not recommended
• PET and SPECT imaging not recommended for routine
  use in the diagnosis of dementia
    – “Little evidence to support the routine use of PET in pts with
      suspected or established dementia” JAGs 51: 2003 Clinical criteria
      accurate in 90%

*PET scan may help clarify Alzheimer’s vs. other types dementias in those
   already fully evaluated
*SPECT scan may help identify early dementia but studies are limited



                                                                            12
    Potential Reversible Causes
• Neoplasms             • Nutritional disorders
• Metabolic disorders   • Psychiatric disorders
• Trauma                • Normo-pressure
• Toxins                  Hydrocephalius
• Infections              (NPH)
• Autoimmune
  disorders
• Drugs


                                                  13
         Distinguishing Dementia
• Delirium versus Dementia
  –   Acute onset
  –   Cognitive fluctuations over hours or days
  –   Impaired consciousness and attention
  –   Altered sleep cycles
• Depression versus Dementia
  – Demonstrate  motivation during cognitive testing
  – Express cognitive complaints that exceed measured
    deficits
  – Maintain language and motor skills


                                                        14
  SPECIFIC
DEMENTIAS…




             15
           Alzheimer’s Dementia
• Dementia NOT caused by other medical/mood or CNS
  disorder
  – Definitive diagnosis is on brain biopsy/autopsy
      •   Neurofibrillary tangles and senile plaques
      •   Reduced cerebral production of choline acetyl transferase
      •   Decreased Acetylcholine synthesis
      •   Marked cholinergic deficit
  – DSM-IV criteria
      • Cognitive deficits including impaired memory, executive function and
        aphasia/apraxia/agnosia
      • Gradual onset, continuing decline; impaired social/occupational
        function




                                                                           16
     SYMPTOMS & SIGNS OF AD
•   Memory impairment
•   Gradual onset, progressive cognitive decline
•   Behavior and mood changes
•   Difficulty learning, retaining new information
•   Aphasia, apraxia, disorientation, visuospatial dysfunction
•   Impaired executive function, judgment
•   Delusions, hallucinations, aggression, wandering




                                                             17
       Alzheimer's disease
• CT scanning aids diagnosis by excluding
  multiple infarction or a mass lesion.
• MRI shows bilateral temporal lobe atrophy.
• SPECT usually shows temporoparietal
  hypoperfusion.
The brain in AD
                       microscopic
                       view:
                       neurofibrillary
                       tangles and
                       protein deposits




       macroscopic
       view:
       neuronal loss
       appears as
       atrophy
PET scan in Alzheimer’s disease
                                  20
        PROGRESSION OF AD
Mild Impairment             Moderate
• Disorientation for date   • Disorientation for date and
                              place
• Naming difficulties       • Comprehension difficulties
• Recent recall problems    • Impaired new learning,
                              calculating skills
• Mild difficulty copying
                            • Getting lost in familiar areas,
   figures                    wandering
• Decreased insight         • Not cooking, shopping, banking
• Social withdrawal         • Delusions, hallucinations
• Irritability              • Agitation, restlessness, anxiety,
                              aggression
• Mood change               • Depression
• Problems managing         • Problems with dressing and
   finances                   grooming
                            • Aphasia and apraxia



                                                             21
       PROGRESSION OF AD

Severe Impairment
• Nearly unintelligible verbal output
• Remote memory gone
• Unable to copy or write
• Unable to feed*
• No longer grooming or dressing
• Incontinent
• Unable to Walk
                                        22
Other Dementias……..




                      23
   DSM-IV DIAGNOSTIC CRITERIA
    FOR VASCULAR DEMENTIA
• Development of cognitive deficits manifested by
  both
     • impaired memory
     • aphasia, apraxia, agnosia, disturbed executive function
• Significantly impaired social, occupational function
• Focal neurologic symptoms & signs or evidence of
  cerebrovascular disease
• Stepwise Deterioration (after each event)



                                                                 24
25
    Multi-infarct dementia (MID)
•   This is an overdiagnosed condition which accounts for less than
    10% of cases of dementia.
•   MID is caused by multiple strokes - SILENT STROKES
•   Dementia occurs ’stroke by stroke‘, with progressive focal loss
    of function.
•   Clinical features of stroke profile – hypertension, diabetes, etc.
    – are present. More often in males.
•   Diagnosis is obtained from the history
    and confirmed by CT or MRI scan
    (the presence of multiple areas of
    infarction).
•   Treatment: Maintain adequate blood
    pressure control, anti-platelet
    aggregants (aspirin).
DEMENTIA ASSOCIATED WITH
      LEWY BODIES
•   Dementia
•   Visual hallucinations
•   Parkinsonian signs
•   Alterations of alertness or attention




                                            27
       DLB-Other Features
• Neuroleptic Sensitivity (ie Olanzapine)
• Falls
• Early incontinence




                                            28
           OTHER DEMENTIAS
• Alcoholic Dementia
   – Direct effects of alcohol, Secondary effects of
     alcohol,Wernicke-korsakoff syndrome
• Toxic Metal and Gas Exposure
   – Common exposures: lead, mercury, manganese, arsenic,
     carbon monoxide & carbon disulfide
• Vitamin Deficiencies
   – Vitamins B12, folate, niacin, and thiamine
   – More severe B12 deficiency: subacute combined degeneration




                                                                  29
    Organic causes of dementia
•   Organ Failure (liver, kidneys)
•   Endocrine (hypothyroidism, diabetes)
•   Inflammatory (Lupus)
•   Neurodegenerative causes (multiple
    sclerosis & Huntington’s Chorea)




                                           30
             Normal-Pressure
               Hydrocephalus
• May appear similar to Alzheimer’s…..
• Early treatment may reverse cognitive
  changes before they become permanent
• Triad of symptoms: gait instability, urinary
  incontinence and dementia
  – Wide-based, shuffling gait with poor coordination
  – Incontinence follows gait change, includes urgency
  – Slow thinking/response, decreased spontaneity
• Enlarged ventricles on MRI
  – But no evidence of atrophy: Alzheimer’s shows large
    ventricles due to brain atrophy


                                                          31
    Parkinson Dementia

• Age Onset: 50 to 80; survival 8-15 yrs
• Dementia occurs later in the disease, mild to
  mod.
• Slowness of thought
• Neuropsychiatric symptoms common
• Dysphagia, dysphonia



                                                  32
     Frontotemporal Dementia
• Diagnostic criteria similar to Alzheimer’s
                            BUT
• Onset typically younger (less than 65 years)
• Predominant changes/disturbances in behavior
   – Personality change is a hallmark
   – Changes occur early and progress
• Non-fluent, expressive aphasia common
   – Words remain but are presented in nonsensical format
• Frontal and/or temporal atrophy on MRI
• Early absence of neurologic signs, neurologic signs occur
  with progression

                                                            33
Structural
Changes in
MRI:

Fronto-
temporal
dementias

            34
 Parkinson Plus Dementias
• Dementia occurs early
Additional physical symptoms
• More frontal lobe features
• Earlier onset, more rapid course
• Frontal lobe features
• Poor response to levodopa
• Rapidly accelerates

                                     35
        Multisystem Atrophy
• Onset 55; survival 6-7 years
• Autonomic dysfunction (incontinence,
  impotence, orthostasis)
• Ataxia, dysarthria, contractures, dystonia
• Mild to moderate dementia
• Less tremor




                                               36
Progressive Supranuclear Palsy:
   Dudley Moore (1935-2002)
       • Initially presents similar to
         Parkinsons (earlier age)
       • Difficulty with vision
       • Falls
       • Unable to look down
       • Dysarthria/dysphagia
       • Lifespan 6 years




                                         37
Progressive Supranuclear Palsy
• Onset: late 50 to mid 60, survival 10 years
• Mental slowness, frontal lobe dysfunction,
  pseudobulbar symptoms
• “surprised look”
• Dysarthria, dysphagia
• Often misdiagnosed:late onset of eye sx, missed
  gait and posture instability



                                                38
39
     AIDS dementia complex
• Approximately two-thirds of persons with AIDS
  develop dementia, mostly due to AIDS dementia
  complex.
• In some patients HIV is found in the CNS at
  postmortem. In others an immune mechanism or an
  unidentified pathogen is blamed.
• Dementia is initially of a "subcortical " type.
• CT - atrophy; MRI - increased T2 signal from
  white matter.
• Treatment with Zidovudine (AZT) halts and
  partially revers neuropsychological deficit.
Dementia – diagnostic approach
MANAGEMENT……….




                 42
SYMPTOM MANAGEMENT
• Sundowning
• Psychoses (delusions, hallucinations)
• Sleep disturbances
• Aggression, agitation



                                          43
     NONPHARMACOLOGIC
•   Cognitive enhancement
•   Individual and group therapy
•   Regular appointments
•   Communication with family, caregivers
•   Environmental modification
•   Attention to safety



                                            44
                 PHARMACOLOGIC
• Cholinesterase inhibitors:             • excessive nmda:
    Inhibit cholinesterase at the        •   excitotoxicity and neurotransmittter
                                             damage
      synaptic cleft
                                         •   Memantine is neuroprotective &
•    Offer a small improvement :             disease modifying;
     cognition and activities of daily
     living                              •   for moderate to severe
                                             dementia
•     Examples:
•     donepezil, rivastigmine,           •   alone or in combination
      galantamine
                                         •   Other cognitive enhancers:
• Memantine: (Namenda): N-                   estrogen, NSAIDs, ginkgo, vit. E
  Methyl-D-Aspartate
• Antagonist: A receptor
      activated by glutamate: decr
      nmda



                                                                                    45
IMPROVEMENT w/ NAMENDA




                     46
       TREATING PSYCHOSIS IN
             DEMENTIA
Antipsychotic medications (side effects):
• Higher potency: haloperidol (extrapyramidal symptoms)
• Lower potency: thioridazine (anticholinergic effects,
  sedation, hypotension, constipation, urine retention)
• Atypical antipsychotics: clozapine, risperidone, olanzapine
 Beware new prescribing information on some of the atypical
  antipsychotics!




                                                               47
 ANTIPSYCHOTICS USED IN
       DEMENTIA
Drug                 Starting Dose        Peak Effective
                                             Dose
Clozapine        12.5-25 mg twice daily    100 mg daily
Haloperidol         0.25 at bedtime        3-5 mg daily
Olanzapine      1.25-2.5 mg at bedtime      5 mg daily
Risperidone     0.25-0.5 mg at bedtime    1-1.5 mg daily

   Note: Start low, go slow.

                                                          48
              MANAGING SLEEP
               DISTURBANCES
• Improve sleep hygiene (e.g, consistent bedtime,
  comfortable setting)
• Provide daytime activity, prevent daytime sleeping
• Use bright-light therapy
• Treat associated depression, delusions
• If the above do not succeed, consider:
      • trazodone 25-150 mg
      • nefazodone 100-500 mg
      • zolpidem 5-10 mg
• Avoid benzodiazepines or antihistamines


                                                       49
    MANAGING AGITATION
• Behavioral interventions: distraction,
  supervision, routine, structure
• Behavior modification using rewards
• Pharmacologic interventions:
  antipsychotics, antidepressants, mood
  stabilizers, buspirone, -blockers
• Avoid physical restraints

                                           50
RESOURCES
FOR MANAGEMENT


• Specialist referral to:   • Attorney
      • geriatric           • Day Care, Respite
        psychiatrist          Care
      • Neuropsychologi     • Alzheimer’s
        st                    Association
      • Social worker       • Meals on Wheels

• Physical therapist


                                                  51

				
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