Dementia with Lewy body

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Dementia with Lewy body

• Lancet Neurol 2004 3 19-28

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Introduction

• Dementia affects 7 of patients older than 65
  years and 30 of those aged over 80 years
• DLB is the second most common cause of
  neurodegenerative dementia in the elderly
• Abnormal aggregation of the presynaptic protein
  alpha- synuclein

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Diagnostic concepts

• DLB and PDD have clinical and pathological
  similarity
• 1 year rule is used to separate DLB from PDD
• Onset of dementia within 12 months of
  parkinsonism -gt DLB
• If more than 12 months -gt PDD
• Both disorders have Lewy body

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Clinical and pathological criteria for DLB

• Clinical features in DLB and PDD are similar
• Including fluctuating neuropsychological
  function, predominant visual hallucination
• Heterogeneity of pathological finding in DLB , AD
  , VaD

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Epidemiology

• Prevalence of DLB 0.7 in people aged 65 years
  or older
• 10 of all dementia cases
• Age over 85 yrs -gt prevalence 5.0 and 22 of
  all dementia
• No study about age, sex and risk factor for DLB

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Clinical phenomenology of DLB

• Cognitive
• Cognitive impairment is present in most of cases
  but not all
• Typically recurrent episodes of confusion with
  progressive deterioration
• Combination of cortical and subcortical
  neuropsychological impairment
• Prominent frontosubcortical and visuospatial
  dysfunction ( DDx from AD )
• Fluctuation in cognitive function 50 75
• ( vary over minutes or days )

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Psychiatric

• Common
• Predominantly visual hallucination, auditory
  hallucination, delusion, apathy and anxiety
• Present early
• Persist (over 20 to 52 weeks)
• Hallucination similar to PDD vivid , colorful
• 3-dimensional, mute image of animate objects
• Visual hallucination associated with deficit in
  cortical acetylcholine and better response to
  AchE inhibitors

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Neurological

• Extrapyramidal signs 25-50
• Severity of parkinsonism equals to PD
• Axial bias greater postural instability and
  facial impassivity, less tremor
• non- dopaminergic motor involvement (speech,
  posture, balance ) associate with dementia

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Sleep

• REM sleep behaviour disorder vivid and
  frightening dreams
• Frequent associated with synucleinopathy eg. DLB,
  PD , MSA
• REM- sleep wakefulness dissociation daytime
  hypersomnolence, hallucination, cataplexy

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Autonomic failure

• Orthostatic hypotension
• Carotid sinus hypersensitivity
• Dizziness, presyncope, syncope, falls
• Autonomic dysfunction risk for falls 65
• Urinary incontinence

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Disease progression and survival

• No difference between DLB and AD in survival
  from onset until death or may be worse in DLB
• Severe extrapyramidal signs and frequent fall -gt
  rapid disease progression or poorer survival is
  not known

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Clinical diagnosis of DLB

• Clinical assessment history, full mental,
  cognitive, and neurological examination
• Consensus Guidelines for the clinical diagnosis
  of probable and possible DLB
• Meeting of International Psychogeriatric
  Association and European Movement Disorder
  Society Participants

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Consensus Guidelines for the clinical diagnosis
of probable and possible DLB

• Central features
• Progressive cognitive decline of sufficient
  magnitude to interfere with normal social and
  occupational function. Prominent or persistent
  memory impairment does not necessary occur in the
  early stage but is evident with progression in
  most cases. Deficits on tests of attention,
  fronto- subcortical skill and visuospatial
  ability are prominent.

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Consensus Guidelines for the clinical diagnosis
of probable and possible DLB

• Core features ( 2 core features essential for
  probable, 1 for possible DLB )
• 1. Fluctuating cognition with variation in
  attention and alertness
• 2. Recurrent visual hallucination typically
  well formed and detailed
• 3. Spontaneous features of parkinsonism

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Consensus Guidelines for the clinical diagnosis
of probable and possible DLB

• Supporting features
• - repeated falls
• - syncope
• - transient loss of consciousness
• - neuroleptic sensitivity
• - systematized delusion
• - hallucinations in other modalities
• - REM sleep behaviour disorder
• - depression

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Consensus Guidelines for the clinical diagnosis
of probable and possible DLB

• Features less likely to be present
• - History of stroke
• - Any other physical illness or brain
  disorder to interfere cognitive performance

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Differential diagnosis

• Alzheimers disease
• Vascular dementia
• PDD
• Parkinson plus syndrome (PSP, MSA)
• Creutzfeldt- Jakob disease

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Laboratory and neuroimaging

• EEG early slowing, epoch-by-epoch fluctuation ,
  transient temporal slow-wave activity
• MRI hippocampal and medial temporal lobe
  volume are preserve
• SPECT occipital hypoperfusion
• Dopamine transporter loss in caudate and putamen
  (sens 83 , spec 100 )

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AD
DLB
Coronal MRI in AD and DLB matched for dementia
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SPECT of dopamine transporter at level of striatum
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Pathophysiology of DLB

• Consensus criteria for DLB include
• - ubiquitin immunohistochemistry
• - 3 categories brainstem- predominant
• limbic- predominant
• neocortical-
  predominant
• Alpha- synuclein is a better marker

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• Lewy bodies are intraneuronal cytoplasmic
  inclusion stain with ubiquitin
• Composed of
• straight neurofilament
• Surrounding amorphous material

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• Alpha-synucleinopathies
• - DLB
• - PD with or without dementia
• - primary autonomic failure

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Pathophysiology of DLB

• Number of cortical LB not associated with
  severity and duration of dementia
• Lewy neurites and neurotransmitter deficit link
  to clinical symptoms
• Anterior and inferior temporal lobe are
  associated with well-formed visual hallucination
• Nigrostriatal pathway -gt parkinsonism

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Pathophysiology of DLB

• Most of DLB have AD pathology cortical amyloid
  plaques, neurofibrillary tangles
• LB occurs up to 2/3 of early onset
• familial AD
• Numerous cortical LB -gt functional neuronal
  impairment

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Management of DLB

• 1. Accurate diagnosis
• 2. Identification of target symptom with patient
  and carer
• 3. Non-pharmacological interventions
• 4. Pharmacological intervention

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Management of DLB

• Target symptom include
• - extrapyramidal motor feature
• - cognitive impairment
• - neuropsychiatric features (hallucination
  depression , sleep disorder, behavioral
  disturbance )
• - autonomic dysfunction

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Non-pharmacological management of DLB

• Psychosocial treatment
• 1. Maintain alliance with patient and family
• 2. Monitor safety and intervence
• 3. Decrease the hazards of wandering
• 4. Educate patient and family
• 5. Advice family source of care and support
• 6. Guide family in financial and legal issues

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Pharmacological management

• Antiparkinsonian drug lowest dose of levodopa
  monotherapy
• Neuroleptic agent provoke severe EPS
• 50 in DLB, increase MR 2-3 times
• low dose atypical antipsychotic drugs
• Cholinesterase inhibitor significant improved
  in fluctuating cognitive impairment, visual
  hallucination, apathy
• , anxiety, sleep disturbance

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Global awareness of DLB and educational and
treatment needs

• Most dementia research in North America,
  Australia and Europe
• Developing countries -gt less awareness
• Increase morbidity and mortality
• Need diagnostic criteria for PDD
• Need biological markers for DLB
• Educational materials internet

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Conclusions

• DLB is one of neurodegenerative disorder
• Alpha-synucleinopathies
• - DLB
• - PD with or without dementia
• - primary autonomic failure
• DDx from PDD, AD, VaD

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Conclusion

• Elderly with cognitive impairment
• Asking for DLB diagnosis
• - visual hallucination
• - REM sleep behavior
• - repeated falls
• - neuroleptic sensitivity
• Dopaminergic neuroimaging may useful
• Good response to AchE inhibitor
• Avoid neuroleptic drugs

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Thank you for your attention