Dementia with Lewy Bodies

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Dementia with Lewy Bodies

• Leonard Griffiths
• Thursday 22nd Nov 07

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Case Mrs ME

• 86?
• Admitted 2/10/07 with 2/12 Hx worsening mobility
• Leg weakness
• No altered sensation of pain
• Fall noted 6/52 prior to admission
• mechanical sounding
• No LOC/HI/CP/palpitations/SOB
• Recalled incident

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Case Mrs ME

• Intermittent confusion for 5/52 prior to
  admission
• Treated for UTI (although no urinary signs or
  symptoms)

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Case Mrs ME

• PMH
• Registered blind
• Osteoporosis
• Angina
• Hypertension
• Asthma
• Episode of jaundice 40 yrs ago

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PTWR

• Diagnosed weakness of legs
• ?musuloskeletal
• ?UTI

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Abnormal results

• WBC 11.5 Neut 8.2
• Na 128
• U Osmo 566
• U Na lt20
• P Osmo 282
• P Na 132
• ? not SIADH

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Abnormal results

• Urine dip
• Blood
• Leuk
• Protein
• Nitrites
• Lab ve for nitrites and leukocytes
• Culture ? mixed growth suggesting contam.

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Abnormal results

• AMSE
• 8/10
• MMSE 20/28
• GDS 3/15
• i.e. not depressed
• CT brain
• Moderate small vessel disease
• Small L occipital infarct

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SHO WR 6/10/07

• Thought pt had low mood ? d/w consultant ? ref to
  ? liaison
• Felt that new environment and poor eyesight a
  significant factor in agitation

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Consultant WR 9/10/07

• Cogwheeling
• Tremor
• Short shuffling gait
• Leans backwards
• Impression Parkinsonism
• 1/52 domperidone commenced
• Ref. to PD consultant

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SHO WR 11/10/07

• Hallucinating
• Horse woman of the year
• Believed someone gave her eye drops (not
  prescribed)

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PD consultant review

• Tricky mixed picture which is difficult to
  disentangle
• Hallucinations
• Although ?Charles Bonnet in relation to reduced
  eyesight
• Some reduced memory
• ?DLB but has cerebrovascular disease
• Parkinsonism but not typical PD
• tremor rather fine
• balance ? back
• Try madopar, but suspect little to be gained
  from medication

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SHO WR 15/10/07

• Hallucinating
• Relatives
• Monkey

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Progress

• 18/10/07 madopar commenced
• 22/10/07 more confused and hallucinations
  worsening ? madopar stopped rivastigmine
  commenced
• 30/10/07 paranoia and aggressive

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Progress

• 6/11/07 hallucinations worse at night ?
  quetiapine added
• 16/11/07 mood even lower ? venlafaxine added
• Now awaiting community hospital bed

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Diagnosis

• Clinical features reflect anatomical distribution
  of pathology rather than its nature
• Therefore subtle clinical features not helpful

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What is Dementia? ICD-10 definition

• 1. A decline in memory to an extent that it
  interferes with everyday activities, or makes
  independent living either difficult or
  impossible.
• 2. A decline in thinking, planning and organizing
  day-to-day things, again to the above extent.
• 3. Initially, preserved awareness of the
  environment, including orientation in space and
  time.
• 4. A decline in emotional control or motivation,
  or a change in social behaviour, as shown in one
  or more of the following emotional lability,
  irritability, apathy or coarsening of social
  behaviour, as in eating, dressing and interacting
  with others.
• Maj, M.. 2002., Dementia, Second Edition
  online. 2nd Edition. Wiley. Available from
  http//mil.ingramdigital.com/Browse/open.asp?ID10
  147locCover 15 November 2007

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Wikipedia definition

• Dementia is the progressive decline in cognitive
  function due to damage or disease in the brain
  beyond what might be expected from normal ageing.
• http//en.wikipedia.org/wiki/Dementia

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Dementia

• Alzheimer's
• Vascular
• Lewy body
• Alcohol
• Pure vascular
• Frontotemporal lobar degenerations
• Creutzfeldt-Jakob disease
• Dementia pugilistica
• Moyamoya disease

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Nomenclature

• Diffuse Lewy body Disease
• Cortical Lewy body Disease
• Lewy Body Dementia
• Senile Dementia Of Lewy Type
• Lewy Body Variant of Alzheimer's Disease
• Dementia with Lewy Bodies (preferred)

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Dementia with Lewy Bodies

• Describes several common disorders causing
  dementia
• The main features of these conditions are
• development of dementia with features overlapping
  with those of Alzheimer's disease
• development of features of Parkinson's disease
• fluctuation in severity of condition on a
  day-to-day basis
• early development of hallucinations

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Neuropathology

• Degeneration of substantia nigra
• Degeneration of the cortical areas of the brain
  with many or all of the features seen in
  Alzheimer's disease
• Remaining nerve cells contain abnormal structures
  called Lewy bodies

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Lewy Bodies

• Abnormal aggregation of proteins, including
• alpha-synuclein, neurofilament and ubiquitin
• PD
• Dementia with Lewy bodies
• MSA
• Amyotrophic lateral sclerosis
• Hallervorden-Spatz syndrome
• Core, body, halo
• Variations in shape

Synucleopathies
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www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG
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www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG
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Tonus und Bewegund (Muscle Tone and Movement)
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Frederich Heinrich Lewy
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opm.phar.umich.edu/images/proteins/1xq8.gif
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Alpha-synuclein

• Abundant CNS protein
• Composed of 140 amino acids
• Alpha form of synuclein is the only form capable
  of aggregating into fibrillar structures in vitro
• Beta-synuclein is not localized in Lewy bodies,
  it may have a role in regulating alpha-synuclein
  metabolism or aggregation

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faculty.uncfsu.edu/shan/07282020c20006a.gif
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Normal role of alpha-synuclein

• Synaptic plasticity
• Negative regulation of dopamine neurotransmission
• Protection at nerve terminals during injury
• Trafficking of cargo in the ER/Golgi complex

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Alpha-synuclein in disease

• Ubiquitinated with no loss of proteasome
  function, suggesting there is an excessive
  accumulation of alpha-synuclein that overwhelms
  the proteolytic machinery (Tofaris, et al. 2003).
  This may promote the formation of Lewy bodies

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Presenting Features DLB

• Dementia normally presenting feature
• Minority present with parkinsonism
• Some with psychiatric disorder without dementia
• Others with orthostatic hypotension, falls or
  transient disturbances of consciousness
• Sporadic (rarely familial)

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Common Features

• Fluctuation in cognitive performance and
  functional ability
• Variations in attention and level of
  consciousness
• Visual hallucinations in two-thirds

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Gelder, Michael G. Lopez-Ibor, Juan Jose
Andreasen, Nancy C.. 2003., New Oxford Textbook
of Psychiatry, Volume 1 online. New Edition.
Oxford University Press. Available from
http//www.myilibrary.com/Browse/open.asp?ID14714
loc416 15 November 2007
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Sensitive signs for bedside diagnosis

• Psychiatric vs. cognitive symptoms
• Hallucinations
• Delusions
• Fluctuant cognitive state

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Hallucinations

• Repeated visual hallucinations are present in
  about two-thirds of patients
• vivid, colourful, and sometimes fragmented
  figures of people and animals
• often complex, detailed and rapidly moving
• can involve scenes and bizarre situations
• can start with misinterpretations and are usually
  short
• often occur at night
• usually not distressing to the patient

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Treatment

• No cure
• Cognitive symptoms ? acetylcholinesterase
  inhibitors, such as donepezil and rivastigmine
• May reduce psychiatric and motor symptoms
• Rigidity ? levodopa

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Summary

• Third most common dementia
• Central feature is progressive cognitive decline
• Pronounced fluctuations
• Recurrent visual hallucinations
• Parkinsonism
• Symptoms caused by Lewy Bodies comprised of bits
  of alpha-synuclein

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