Dementia with Lewy Bodies

Leonard Griffiths

Thursday 22nd Nov 07

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

Case: Mrs ME

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

symptoms)

Case: Mrs ME

PMH• ‘Registered blind’

• Osteoporosis

• Angina

• Hypertension

• Asthma

• Episode of jaundice 40 yrs ago

PTWR

Diagnosed ‘weakness of legs’• ?musuloskeletal

• ?UTI

Abnormal results

WBC 11.5; Neut 8.2 Na+ 128

• U Osmo 566

• U Na+ <20

• P Osmo 282

• P Na+ 132 not SIADH

Abnormal results

Urine dip• Blood +

• Leuk +++

• Protein +

• Nitrites +

Lab +ve for nitrites and leukocytes• Culture ‘mixed growth suggesting contam.’

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

SHO WR 6/10/07

Thought pt had low mood d/w consultant ref to Ψ liaison• Felt that ‘new environment and poor eyesight

a significant factor in agitation’

Consultant WR 9/10/07

Cogwheeling Tremor Short shuffling gait ‘Leans backwards’

• Impression: Parkinsonism

• 1/52 domperidone commenced

• Ref. to PD consultant

SHO WR 11/10/07

Hallucinating• “Horse woman of the year”

• Believed someone gave her eye drops (not prescribed)

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’

SHO WR 15/10/07

Hallucinating• Relatives

• Monkey

Progress…

18/10/07 madopar commenced

22/10/07 more confused and hallucinations worsening madopar stopped & rivastigmine commenced

30/10/07 – paranoia and aggressive

Progress…

6/11/07 – hallucinations worse at night quetiapine added

16/11/07 – mood even lower venlafaxine added

Now awaiting community hospital bed

Diagnosis

Clinical features reflect anatomical distribution of pathology rather than its nature

Therefore subtle clinical features not helpful

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?ID=10147&loc=Cover 15 November 2007

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

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

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)

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

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’

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

SynucleopathiesSynucleopathies

www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG

www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG

Tonus und Bewegund (Muscle Tone and Movement)

Frederich Heinrich Lewy

opm.phar.umich.edu/images/proteins/1xq8.gif

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

faculty.uncfsu.edu/shan/0728%2020c%20006a.gif

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

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

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)

Common Features

Fluctuation in cognitive performance and functional ability

Variations in attention and level of consciousness

Visual hallucinations in two-thirds

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?ID=14714&loc=416 15 November 2007

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?ID=14714&loc=416 15 November 2007

Sensitive signs for ‘bedside’ diagnosis

Psychiatric vs. cognitive symptoms• Hallucinations

• Delusions

Fluctuant cognitive state

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

Treatment

No cure

Cognitive symptoms acetylcholinesterase inhibitors, such as donepezil and rivastigmine• May reduce psychiatric and motor symptoms

Rigidity levodopa

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