Dementia is……

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					Dementia with Lewy Bodies



    Preetha Krishnan RN (EP)
  Nurse Practitioner, LTC, WRHA
           Objectives
Introduction
History of LBD
Other names of LBD
Neuropathology &Neurochemistry
Epidemiology
Diagnostic tests
Diagnostic criteria
Differential diagnosis
               Objectives
Functional disabilities
Management
  Non pharmacological
  Pharmacological
   • Cognitive impairment
   • Parkinsonism
   • Psychotic symptoms
DLB vs. AD vs. PDD
Conclusions
              Dementia
Latin word “ de mens”- without mind
  “The memory lost and the judgment failing,
  so that they become as they were in their
  infancy” (Andre-du Laurens, 1558-1609)
A syndrome
  “A global deterioration of mental functioning
  in its intellectual, emotional, social &
  cognitive aspects”
Chronic & progressive in nature
Dementia is an epidemic
 Common Types of Dementia
Alzheimer’s disease (AD)         55-65%
Dementia with Lewy Bodies(DLB)   15-20%
Vascular Dementia (VaD)           10-15%
Fronto Temporal Dementia (FTD)     5-10%
Other types of dementia               5%
 Dementia with Lewy Bodies
Second most common cause of dementia
A neurodegenerative form of dementia
A clinical syndrome
  Not a neuropathological diagnosis
Clinical/pathological features overlap with
Parkinson's’ disease & Alzheimer’s disease
    Why DLB is important?
Clinical presentation & course of disease
are different from other dementias
Complex mix of cognitive, psychiatric &
motor symptoms
Management of symptoms is complicated
Requires more resources than AD
Earlier institutionalization than AD
                     History
1817- James Parkinson
    • Essay on the ‘Shaking palsy’ ‘paralysis agitans’

1912- Friedrich Heinrich Lewy
    • Intracytoplasmic inclusion bodies in the brain

1919- Tretiakoff
    • Introduced Lewy bodies (LB) (corps de Lewy)
1938- Hassler
    • Clinical syndrome associated with cortical LB
1958- Annual meeting of the American
      Association of Neuropathologists
    • Dementia directly to the cortical LB
                 History
1961- Okazaki
   • First case report on the relation between cortical
     Lewy bodies and dementia
1995- The consensus conference in Newcastle
   • Designation of Dementia with Lewy Bodies (DLB)
1996- First international workshop on DLB
   • Diagnostic criteria for DLB
2003- Third international workshop on DLB
   • Current revised diagnostic criteria
    Other Diagnostic Labels
Alzheimer’s disease with Parkinson's disease
changes
Alzheimer’s disease with incidental Lewy bodies
Lewy body variant of Alzheimer disease
Diffuse Lewy body disease
Dementia associated with cortical Lewy bodies
Diffuse cortical Lewy body disease
Senile dementia of Lewy body type
 Neuropathology-Language
Lewy bodies (LB)
  Spherical intracytoplasmic eosinophilic
  neuronal inclusion bodies
  Can be detected with routine
  histopathological staining
  Neuropathology-Language
Lewy neurites (LN)
  Inclusion bodies similar to LB, found in axon
  of the affected neuron
  Not visible with routine histopathological
  statining
  Neuropathology-Language
Alpha-Synuclein
  Primary protein component of both LB & LN
  Detected with immunohistochemical staining
           Neuropathology
An alpha synucleinopathy
Lewy bodies & Lewy neurites
   Neocortex, limbic cortex, subcortical nuclei & brain
  stem
Neuronal loss in substantia nigra & nucleus
basalis Meynert
Alzheimer's’ pathology
  Presence of senile plaque with diffuse amyloid deposit
Spongiform changes or microvacuolation
             Neuropathology
Spongiform changes/
                      AD pathology with plaques
 Microvacuolation
           Neurochemistry
A cholinegic/dopaminergic syndrome
  Defect in dopamine & acetylcholine
  neurotransmission
  Reduction in cortical choline acetyl transferase
  Reduction in dopamine
  Reduction in D2 receptors
                Epidemiology
Prevalence
  0-5% in general population
  0-30% in all dementias
Incidence
  0.1%/year in general population
  3.2%/year for all new dementias
Range of onset
  60-90 years
Mean onset
  75 years
Male > female
        Diagnostic Studies
No plasma or CSF biomarkers
Neuro-imaging can be helpful in supporting
the diagnosis
  MRI: preservation of medial temporal lobe
  volume
  PET: occipital hypometabolism
  SPECT: occipital hypoperfusion & dopamine
  transporter loss in the caudate & putamen
      Neuroimaging
MRI
          AD


          DLB
                 SPECT
     Diagnostic Criteria
Central feature
  Progressive cognitive decline
  Prominent or persistent memory
  impairment
  Prominent deficits on tests of attention and
  of frontal-subcortical skills and visuospatial
  ability
       Diagnostic Criteria
Core features
  Fluctuating cognition with variations in
  attention & alertness
  Recurrent visual hallucinations
  Spontaneous motor features of parkinsonism
       Diagnostic Criteria
Suggestive features
  REM sleep behavior disorder (RBD)
  Severe neuroleptic sensitivity
  Low dopamine transporter uptake by SPECT or
  PET imaging
        Diagnostic Criteria
Supportive features
  Repeated falls & syncope
  Transient unexplained loss of consciousness
  Severe autonomic dysfunction
  Hallucinations in other modalities
  Systematized delusions
  Depression
        Diagnostic Criteria
A diagnosis of DLB is less likely
        In the presence of
  Stroke
  Any other illness or brain disorder sufficient to
  interfere with cognitive performance
  First time appearance of parkinsonism at a
  stage of severe dementia
     Differential Diagnosis
Delirium
Alzheimer’s disease
Parkinson’s disease with dementia (PDD)
Vascular dementia
Charles-Bonnet syndrome
   Functional Disabilities in DLB
     Acting out dreams
                            Sleep
                           disorder
                                            Orthostatic hypotension
   Fluctuations
                                            Syncope, Constipation
   in attention

                                       Autonomic dysfunction
Cognitive dysfunction       DLB          Motor dysfunction
Memory, attention
                                               Parkinsonism
Executive function

         Delusions       Psychiatric
                                            Visual
         Depression       disorder      Hallucinations
          Anxiety
    Cognitive Dysfunction
Attentional & executive dysfunction
Visuo-perceptual & visuo-constructive
impairment
Semantic & episodic memory impairment
Pentagon coping impaired than AD
Better verbal recall than AD
Worse on praxis than AD
      Cognitive Dysfunction
Fluctuating cognition
  Occurs in 60-80% of people
  can be a presenting symptom
  Waxing & waning
  Lasts for minutes, hours or days
  Mimics delirium
  Difficult to capture with clinic visits
The Mayo Fluctuations Questionnaire
 Questionnaire for caregivers
 Four item composite
   Drowsiness & lethargy all the time or several
   times a day
   Daytime sleep of two or more hours
   Staring into space for long periods
   Times when person’s flow of ideas seems
   unclear, disorganized or not logical
Fluctuations Composite Score
 Three or more ‘yes’ responses
   Clinical diagnosis of DLB vs. AD
   83% positive predictive value
 Less than three ‘yes’ responses
   Clinical diagnosis AD vs. DLB
   70% negative predictive value
Visual Hallucinations (VH)
Occurs in 60-70% cases & prior to the onset of dementia
Occurs early on & persist throughout the illness
Presenting feature in 35-65% of cases
Complex detailed brightly colored three dimensional
images
Mainly images of people & animals
Images of children, fire,insects & birds can occur (less
frequently)
Diurnal pattern with more severe VH in the evening &
at night
Co-occurrence of auditory hallucinations (speech or
noises)
   Psychiatric Dysfunction
Delusions
  49 % of DLB vs. 31% AD
  Early in the course of the disease
  Delusional misidentification is common
Major depression
  24-29% of DLB vs. 9-16% AD
Anxiety
  Occurs mainly in early & late stages
  Seen in 80% of cases
      Motor Dysfunction
Parkinsonism
10-78% cases at presentation
40-100% at some stage of the illness
An axial bias
  Greater facial impassivity & postural
  instability
  Less common rest tremor
‘Non-dopaminergic’ motor involvement
   Autonomic Dysfunction
Unexplained falls & syncope
Orthostatic hypotension
Urinary incontinence
Constipation
            Sleep Disorder
Rapid eye movement (REM) sleep behavior
disorder (RBD)
Lack of motor inhibition
Prominent motor activity
‘Act out in dreams’
Vivid & frightening dreams
Precede many years of cognitive impairment
          Management of DLB
A four step approach

                          Diagnosis

                     Identification of
                  Functional disabilities

                     Management
                  Non-pharmacological
                        Management
                       Pharmacological
            Management
Education & support to family/the person
Identify key functional disabilities
Focus on most disabling symptoms
Assess caregiver burden
Non-pharmacological approach first
Pharmacological approach
            Management
Before interventions clarify
  Who need to be treated?
  Whose problem is being treated?
  Whose reality is being considered?
  Whose needs & preferences take precedence?
Answers to these will determine the
ultimate goal.
   Management of Disabilities
Multidisciplinary team
                          Family/
                         Care givers
        Psychiatrist                     Neurologist


  Occupational
                            DLB               Geriatrician
   therapist
          Primary
                                         Community
            Care
                                          resources
          Provider     Physiotherapist
     Non-Pharmacological
Focus on interactions between person &
environment
Enhance cognition & activities of daily
living
Reduce psychiatric & behavioral problems
Decrease burden on caregivers
Increase safety
Maximize functional potentials
Non pharmacological management
          Examples
Memory/mobility aids
Reality orientation
Enhanced communication
Staffing & staff training
Pet therapy
Family videotapes
One to one interaction
Stimulus control
Home like environment
Activity programs
Optimize light/noise, reduce glare
 Pharmacological Management
No disease- modifying therapies
Symptomatic treatment
  Cognitive impairments, psychosis & motor symptoms
A therapeutic challenge
  Treatment for one symptom worsen the other one
  Compromise between a mobile & psychotic person or a
  immobile & non psychotic person
Use the lowest dose of agent if needed
Monitor adverse effects closely & regularly
         Cognitive Impairment
Cholinesterase inhibitors (ChEI)
  The gold std treatment for cognitive & psychiatric
  symptoms
   • Impaired attention, delusions, anxiety & hallucinations
   • Presence of VH predict a good repose to ChEI
Effective & relatively safe
Many tolerated in standard dose
NMDA (glutamate) antagonist
  Memantine
  Mixed results, need more research
            Parkinsonism
Only treat if symptoms interfere with life
Levodopa is the main agent
Start at lowest dose and increase with
caution
Worsening of attention & visual
hallucinations
    Psychiatric Symptoms
Visual hallucinations, delusion &
agitation
   • No treatment needed if VH are non-threatening
     & not interfere with functions
Taper or stop dopaminergic agents
ChEI or antipsychotics can be used
Avoid typical antipsychotics
Use atypical antipsychotics at low dose
        Psychiatric Symptoms
Watch for neuroleptic sensitivity
   • Occurs in 50% of cases
   • Within two weeks of initiation or dose increase
Life threatening adverse effects
   • Sedation, immobility, rigidity, postural instability,
     falls & increase in confusion
   • Unable to maintain adequate fluid/food intake
   • 2-3 fold increase in mortality
            Neuropathology
          DLB vs. AD vs. PDD
Brain       Limbic/        Amyloid          Neuro-
stem        Cortical       Plaques         Fibrillary
LBs          LBs                            Tangles
 PDD

   Dementia with Lewy bodies



                               Alzheimer’s disease
          Cognitive Profile
         DLB vs. PDD vs. AD
Memory impairment is more in AD
Executive impairments is more in DLB
Attention deficits is more in PDD
Visuospatial impairment is less in AD
Disruptive behaviors are more in AD
MMSE decline one point per year in PDD
MMSE decline per year is same in AD & DLB
  3-4 points/year
            DLB vs. PDD
           “The 1-year rule”
If cognitive impairments predates or occur
within one year of parkinsonism: possible
diagnosis of DLB
If parkinsonism predates dementia by more
than one year: possible diagnosis of PDD
  Prevalence of dementia in Parkinson's disease
  is ~ 3%
  4-5% of all dementia
            Conclusions
Screen all dementia cases for possible DLB,
if at least one core and one suggestive
features present
Accurate diagnosis is the key
Over lap with AD & PD
Good response to ChEI
Avoid neuroleptics
Thank You

				
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