Dementia with Lewy BodiesDisease, Spectrum,Variety of Alzheimers

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Dementia with Lewy Bodies-Disease,
Spectrum,Variety of Alzheimers?

• Dr E Jane Byrne

2
DLB-Outline

• History of the concept
• Epidemiology
• Clinical features

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Lewy Body

• What are they?
• Intracellular inclusion bodies
• Named (by Tretiakoff 1919) after Lewy(1912)
• ContainUbiquitin,alpha-synuclein
• Ubiquitin-a heat-shock protein
• Subcortical and Cortical

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Alpha-Synuclein

• Synucleins
• Soluble proteins- alpha,beta, gamma, synoretin.
• Alpha- Non Amyloid component of the amyloid
  precursor protein gene.
• Spilantini 1997
• Goedert 2000 proposed new classification of
  neurodegenerative disorders

Cortical Lewy Body stained with Antibodies to
alpha synuclein
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History

• Japan
• Described 2 cases with quadriparesis in flexion
  and cortical LBs (Okazaki et al 1961)
• Small case series (50) patients published
  1961-1989
• Yoshimura 1983 Diffuse Lewy Body Disease(Kosaka
  et al 1984)
• Kosaka 3 types (1979,1990) added 4th in(1996)

• Modern era
• Nottingham 1987-1992,first large case
  series,first use of ubiquitn,first diagnostic
  criteria,link to PD (Byrne et al)
• Newcastle1990-present,SDLT,fluctuations
  emphasis/measures,EEG,
• imaging studies,host CDLB-diagnostic
  criteria.(McKeith et al)
• San Diego 1990-presentlewy body variant of
  AD,psychology( Hansen et al)

ReviewGibb et al 1987,Brain1101131-1153
McKeith (2005)
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Concepts

• Entity within a Spectrum of disorders with Lewy
  bodies (Kosaka (1980), Byrne et al
  (1989,1992),McKeith et al (1996)
• Separate Disease (Burkhardt et al (1988), Perry
  et al (1990 )
• Variety of Alzheimers Disease (Hansen et al
  (1990)
• A Synucleinopathy (Boeve et al (2000),Byrne (2001)

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What is Parkinsonian ?

• Classical
• Tremor
• Rigidity
• Postural instability/change
• Bradykinesia
• Gait Abnormality

• Debateable
• Falls
• Fluctuating cognition
• Neuroleptic sensitivity
• Secondary symptoms-Depression,Hallucinations

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Lewy Bodies and Dementia

• Sufficient cause?
• Yes Correlations in all cortical areas with
  Dementia (Lennox et al 1989)
• No Depends on AD pathology / Braak staging (eg
  Ince 2005,Wakisaka et al 2003,Merdes et al 2003).

The senses and intellect being uninjured James
Parkinson 1817
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DLB A Synucleinopathy?

• Synucleinopathies Tauopathies
• Parkinsons Disease Alzheimers Disease
• DLB FTD (sporadic, Familial
• Familial AD-APP PSP)
• PS1, PS2 Corticobasal Degenn
  
• 
  
• Downs Syndrome
• MSA
• Hallervarden-Spatz
• Adapted from- Goedert 1999, Spillantini et al
  1998, Galvin et al 2001

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Synucleinopathies-Agegender
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History-Nottingham Today
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Epidemiology (eg Zaccai et al 2005)

• Community Studies

• Clinical Populations
• Referred for PM 20-28 of dementia cases (Byrne
  et al 1989,Perry et al 1989,Jellinger et al 1996)
• Referrals to OAP/Day Hospitals (with dementia)
  25 (Shergill et al 1994,Stevens et al
  2002Ballard et al 1993)
• Incidence 0.1(commun),2-3.2 (clinical)-(Lopez-Po
  usa et al 2003,Zaccai et al 2005)

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Diagnosis

• Nottingham (Byrne et al 1991)
• Probable Possible
• Probable
• A-Dementia with attentional deficits or PD with
  late dementia or Dementia Pism
• B- No Stroke,No Focal
• C- 3 Pism ( mild or late )
• D- No other cause

• Consensus (McKeith et al 2005)
• Central Dementia with attentional deficits
• Core Fluctuation, Complex visual
  hallucinations, spontaneous parkinsonism.
• Suggestive RBD ,neuroleptic sensitivity,low Da
  transporter uptake in Basal Ganglia
• Supportive (includes)- falls, loc.

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VALIDITY OF FLUCTUATION MEASURES (v AD)
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RBD-Rapid Eye Movement Sleep Behaviour Disorder

• Parasomnia
• Characterised by no atonia, dream enactment,
  sleep related injury

• ICDS (1997)
• Movement associated with dreaming,
• One of - Potentially harmful sleep behaviour
• Acting out of dreams
• Behaviour that continually disrupts sleep

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RBD-recent prevalence studies

• Mignot et al (2002) 0.5-(overall)
• Boeve et al (2001) 39 -(in those with Syn.PSG
  diagnosis)
• Scaglione et al (2005) 33.8 of PD

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RBD-Treatment

• Advice for sleep partners!
• Clonazepam 0.5 mg-1.5 mg nocte
• TCAs(Imipramine-equivocal)
• Melatonin

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RBD -Treatment

• Soap your head with the ordinary yellow soap rub
  it into the roots of the hair until your head is
  just lather all over, tie it up in a napkin, go
  to bed, and wash it out in the morning. Do this
  for a fortnight. Take no tea after 6 P.M. I did
  this, and have never been troubled with
  sleeplessness since. I have lost sleep on an
  occasion since, but one or two nights of the soap
  cure put it all right.(Editorial BMJ 1894)

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DLB- Conclusion

• What is it?
• A Synucleinopathy
• ICC-pragmatic
• A catalyst for nosology

• By their benevolant labours its real nature may
  be ascertained,and appropriate modes of relief,or
  even of cure,pointed out.

James Parkinson 1817