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conf_Lewy-Body-Dementia-Boeve by wanghonghx

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									Dementia with Lewy Bodies


        Bradley F. Boeve, M.D.

     Department of Neurology and
  Alzheimer’s Disease Research Center
              Mayo Clinic
         Rochester, Minnesota
Dementia with Lewy Bodies
             Outline

 • History
 • Epidemiology
 • Clinical features
 • Diagnostic criteria - clinical
 • Diagnostic criteria - pathologic
 • Neuropsychological features
 • Radiologic features
 • Clinical pearls
 • Management
 • Resources
          Dementia with Lewy Bodies
                         History

• 1961 - H. Okazaki first reported Lewy bodies in
  cerebral cortex in patients with dementia
      Okazaki et al, J Neuropathol Exp Neurol, 1961

• 1980s - Ubiquitin immunohistochemistry developed,
  allows visualization or limbic and cortical Lewy bodies

• 1996 - DLB characterized (1st Consensus conference)
     McKeith et al, Neurology, 1996
         Dementia with Lewy Bodies
                        History

• 1997 - -synuclein gene discovered
     Polymeropoulos et al, Science, 1997

• 1997 - -synuclein immunohistochemistry
  developed, allows even better visualization or limbic
  and cortical Lewy bodies
      Spillantini et al, Neurosci Letters, 1998

• 1999 - report from 2nd consensus conference on DLB
     McKeith et al, Neurology, 1999
        Dementia with Lewy Bodies
                      History

• 2005 - report from 3rd consensus conference on DLB
     McKeith et al, Neurology, 2005

• 2006 – 4th consensus conference on DLB held
     Publication pending
   Dementia with Lewy Bodies
              Epidemiology


• Initially thought to be primary cause of
  dementia in 20-25% of patients

• Clinical studies - 10-38% frequency
     most suggest 12-16% frequency

• Autopsy studies - 10-20% frequency
        Dementia with Lewy Bodies
               Topography of Degeneration
Impaired attention, executive
functions, psychomotor speed,     A

visuospatial functioning, mood,
sleep

           A   B   C
                                  B




Ach
                                  C

      DA               5-HT
   Dementia with Lewy Bodies
             Clinical features

Cognitive impairment
 Varying degrees of memory impairment
 Verbal blocking
 Executive dysfunction
 Bradyphrenia
 Spatial/geographic disorientation
 Visual misidentification
 Fluctuations
    Dementia with Lewy Bodies
              Clinical features

Neuropsychiatric features
 Visual hallucinations
 Illusions
 Delusions
 Capgras syndrome
 Depression
 Anxiety
 Auditory, tactile, or olfactory hallucinations
 Agitation or aggressive behavior (usually late
  in the course if present at all)
  Dementia with Lewy Bodies
             Clinical features


Motor dysfunction
 Tremor (often postural and symmetric)
 Bradykinesia
 Rigidity
 Shuffling gait
 Stooped posture
 Difficulty with fine motor skills
 Masked facies
  Dementia with Lewy Bodies
             Clinical features

Sleep disorders
 REM sleep behavior disorder (RBD)
 Excessive daytime somnolence (EDS)
 Insomnia
 Obstructive sleep apnea (OSA)
 Central sleep apnea (CSA)
 Restless legs syndrome (RLS)
 Periodic limb movement in sleep (PLMS)
Dementia with Lewy Bodies
       Clinical features


   Autonomic dysfunction
    Orthostatic hypotension
    Impotence
    Urinary incontinence
    Constipation
          Dementia with Lewy Bodies
                 REM Sleep Behavior Disorder


 Rapid eye movement sleep behavior disorder (RBD)
is characterized by loss of normal skeletal muscle
atonia during rapid eye movement (REM) sleep with
prominent motor activity and dreaming

   Patients appear to “act out their dreams”

     Schenck   et al, 1986   Schenck   et al, 1996   Mahowald   et al, 1990
     Schenck   et al, 1987   Schenck   et al, 1996   Mahowald   et al, 1990
     Schenck   et al, 1990   Schenck   et al, 1997   Mahowald   et al, 1992
     Schenck   et al, 1992   Schenck   et al, 1999   Mahowald   et al, 1996
     Schenck   et al, 1993   Schenck   et al, 2000   Mahowald   et al, 1996
      REM Sleep Behavior Disorder
                 Clinical Features
• Male gender predilection
• Onset age 20-80 years
• Vocalizations, swearing, screaming
• Varies from simple limb jerks to complex motor
behavior; patient and bedpartner injury can occur
• Dreams often involve insects, animals, or humans
• Dreams often involve a chasing or attacking theme
• Exhibited behaviors mirror dream content
REM Sleep Behavior Disorder
        Video examples
REM Sleep Behavior Disorder
        Video examples
    Dementia with Lewy Bodies
         Diagnostic criteria - Clinical

• Presence of dementia
• Impairment often maximal in attention/
  concentration and visuospatial functioning
• Core features*
   – Recurrent fully formed visual hallucinations
   – Fluctuations in cognition or arousal
   – Spontaneous parkinsonism
         * 2+ present for clinically probable DLB,
          1 present for clinically possible DLB
     Dementia with Lewy Bodies
         Diagnostic criteria - Clinical

• Suggestive features:
   – REM sleep behavior disorder (which may
     precede onset of dementia by several years)
   – Severe neuroleptic sensitivity
   – Abnormal (low uptake) in basal ganglia on
     SPECT dopamine transporter scan or
     abnormal (low uptake) MIBG myocardial
     scintigraphy
                       Dementia with Lewy Bodies
                                   Pathologic findings

                               Cortical Lewy bodies




                      H&E                                -synuclein
Photomicrographs courtesy Dennis Dickson, M.D.
              Dementia with Lewy Bodies
                Diagnostic criteria - Pathologic



Lewy body disease
• brainstem
• limbic
• neocortical


                       Photomicrographs courtesy Dennis Dickson, M.D.
                       Dementia with Lewy Bodies
                                Neuropsychological findings

                     Cognitive Domains                                         Impairment
                     Learning & Memory                                              0 to ++
                     Language                                                        0 to +
                     Executive Functions                                          + to +++
                     Visuospatial Functions                                       + to +++


References: Ferman TJ, Boeve BF, Silber MH, Smith GE, Kokmen E, Petersen RC, Ivnik RJ. REM sleep behavior disorder and dementia:
   Cognitive differences when compared to Alzheimer’s disease. Neurology 1999;52:951-957.
Ferman TJ, Smith GE, Boeve BF, Graff-Radford N, Lucas JA, Knopman DS, Petersen RC, Ivnik RJ. Neuropsychological differentiation of
   dementia with Lewy bodies from normal aging and Alzheimer's disease. Clin Neuropsychol 2006;20:623-636.
 Dementia with Lewy Bodies
         Radiologic findings




normal                         DLB
Dementia with Lewy Bodies
     Radiologic findings




AD                         DLB
             Dementia with Lewy Bodies
                        Clinical Pearls

Diagnosis
History
      History of dream enactment behavior
      Pt recognizes cognitive symptoms and is bothered by them
      Often describes “verbal blocking”
      Often have a history of depression, particularly late onset
      Sometimes have history of late-onset bipolar disorder
             Dementia with Lewy Bodies
                        Clinical Pearls

Diagnosis

Exam
       Preserved recall on MMSE or STMS
       Poor copy of overlapping pentagons, clock, cube, Rey-O
       Masked facies, mild bradyphrenia and bradykinesia
       Symmetric rigidity
       Tremor more postural than at rest
       Reduced armswing while walking
             Dementia with Lewy Bodies
                        Clinical Pearls

Diagnosis
Ancillary Tests
      Neuropsychologic profile of impairment
      MRI more normal than not

Management
    Diagnose and treat sleep disorders
    Sometimes robust improvement with AChEI
    Atypical neuroleptics for refractory hallucinations and
      delusions, avoid haloperidol
   Dementia with Lewy Bodies
              Clinical Pearls


Necker cube                Clock showing 11:10

                                     11   12   1
                                10                 2
                            9                          3
                                8                  4
                                     7         5
                                          6
Dementia with Lewy Bodies
        Clinical Pearls

 Rey-Osterrieth Complex Figure
Dementia with Lewy Bodies
       Clinical Pearls
              Dementia with Lewy Bodies
                          Management

Consider symptoms as they relate to:
• cognitive impairment
• neuropsychiatric features
                                  Ask patient/family to
• motor features                  prioritize the most
• sleep disorders                 troublesome issues they
                                  seek to change
• autonomic dysfunction
• medical issues
             Dementia with Lewy Bodies
                          Management

Cognitive impairment
 Varying degrees of memory
                                      Management
  impairment
 Verbal blocking                     Education and counseling
 Executive dysfunction
 Bradyphrenia                        Therapies:
                                      Aricept, Razadyne, Exelon
 Spatial/geographic disorientation   Sinemet, Mirapex
 Visual misidentification            Provigil, Ritalin
 Fluctuations
             Dementia with Lewy Bodies
                        Management


Neuropsychiatric features         Management
 Visual hallucinations
 Illusions                       Education and counseling
 Delusions
 Capgras syndrome                Therapies:
 Depression                      Aricept, Razadyne, Exelon
                                  SSRIs
 Anxiety
                                  Seroquel, Zyprexa
 Agitation/aggressive behavior
              Dementia with Lewy Bodies
                          Management


Motor dysfunction                     Management
 Tremor
                                      Education and counseling
 Bradykinesia
 Rigidity                            Therapies:
 Shuffling gait                      Sinemet, Mirapex
 Stooped posture
 Difficulty with fine motor skills
 Masked facies
              Dementia with Lewy Bodies
                            Management

Sleep disorders                      Management
 REM sleep behavior disorder
                                     Education and counseling
 Excessive daytime somnolence
 Insomnia                           Therapies:
 Obstructive sleep apnea            Clonazepam, Melatonin
 Central sleep apnea                Provigil, Ritalin
                                     Trazodone, Ambien
 Restless legs syndrome             nasal CPAP
 Periodic limb movement in sleep    oxygen, temazepam
                                     Mirapex, Sinemet
           Dementia with Lewy Bodies
                         Management


Autonomic dysfunction            Management
 Orthostatic hypotension
                                 Education and counseling
 Impotence
                                 Therapies:
 Urinary incontinence
                                 Midodrine, Florinef, salt
 Constipation                   Viagra
                                 Detrol, Ditropan
                                 Senokot, Dulcolax
             Dementia with Lewy Bodies
                            Resources

         Treatment of Lewy Body Dementia at Mayo Clinic
     http://www.mayoclinic.org/lewy-body-dementia/index.html

                 Lewy Body Dementia Association
                 http://www.lewybodydementia.org

        NINDS Dementia With Lewy Bodies Information Page
http://www.ninds.nih.gov/health_and_medical/disorders/dementiawithl
                          ewybodies_doc.htm

                 Fact Sheet on Lewy body dementia
      http://dementia.ion.ucl.ac.uk/candid/factsheets/facts4.htm

								
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