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Lecture 10: Dementia Lewy bodies (neuropsychology of ageing) $3.22
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Lecture 10: Dementia Lewy bodies (neuropsychology of ageing)

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This lecture contains all the information from the tenth lecture of the course Neuropsychology of Ageing at the VU. The summary is supplemented with pictures from the slides and extensive notes from the professor.

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  • May 19, 2021
  • 9
  • 2020/2021
  • Class notes
  • M.milders
  • All classes
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HC10: Dementia with Lewy Bodies

This form of dementia is the second most prevalent neurodegenerative form of dementia
 Most frequent neurodegenerative dementia after AD
 Third most common form of dementia, after AD and vascular dementia
o 5-20% of dementia cases
 First described in 1961

The symptoms usually appear after the age of 60, an early onset is rare. Besides that, there
is no increase in prevalence with age, higher age does not necessarily mean more cases of
dementia with Lewy Bodies. The mean survival time is 8-10 years.

Main features and where Lewy bodies is different from earlier discussed forms of dementia:
 Progressive cognitive decline
 Core features:
o Parkinsonism
o Visual hallucinations
o Fluctuations cognitive functioning and arousal

Neuropathology
Lewy bodies = abnormal aggregates
of proteins inside nerve cells.
The protein is not Tau this time! It's
alpha-synuclein. This is a protein
which is present in a normal healthy
brain. The function is not fully clear
yet. The Lewy bodies are made of this
protein.

These proteins start to clump together
and form Lewy bodies, which will
interfere with normal cells and eventually these
normal cells will die. The reason why the proteins
start to clump together is yet unclear.

 Lewy neurites are a common feature in DLB
o Neurites containing abnormal alpha-
synuclein
o Neurite: any projection from cell body
(axon, dendrites)

DLB is an example of a class of neurodegenerative diseases that have the same underlying
cause  synucleinopathies. Another example is Parkinson’s Disease (PD). Lewy bodies and
Lewy neuritis are also found in the nerve cells with PD patients.
Similarities between DLB and PD
 Symptoms of DLB, PD and PD dementia overlap. There are effects on cognition,
movement and behavior.

, Braak et al. (2003): staging LB pathology: I – VI
peripheral NS – brainstem – cortex
LB pathology in DLB similar as PD:
- Most autopsy cases: LB in cortical areas

The distribution of the LB start to spread across
the brain starting in the brainstem and then
gradually moving into the cortex. With increasing
stages, the distribution of LB spreads out more
and more widely

The LB in DLB mostly found in cortex, limbic
areas, and subcortical areas (locus coeruleus,
substantia nigra, nucleus basalis of Meynert)

LB in PD mostly found in substantia nigra only

The LB are found in 20-35% of older persons
with dementia, not just DLB. Lewy bodies are not
common in healthy persons!

AD pathology (amyloid plaques): in up to 75-90% of patients with DLB. Tangles are less
common in DLB

There is a loss of cholinergic neurons and depletion (reducing levels) of choline levels in the
brain
 The cholinergic deficit is more pronounced in DLB than in AD. The nucleus of
Meynert, which is part of the production chain of acetylcholine, this area is affected in
both diseases! But more pronounced in DLB.
 Cholinergic deficit is mostly early in the disease
Cholinergic depletion is a factor in symptoms of early DLB: reduced alertness and attention,
visual hallucinations. This also means that similar medication for AD, which is there for
increased levels for acetylcholine in the brain, are also being used for DLB and often with the
same effects  increasing ACTh levels  acetylcholinesterase inhibitors, can have positive
effects on symptoms.

In PD you immediately have to think about depletion of dopamine levels. LB are also found
in the same area as in PD, the substantia nigra, therefore it is implicated that there is also a
reduction in dopamine.
 Available dopamine has less impact
 Weak response to dopaminergic drugs
In PD, dopaminergic drugs can be effective in alleviating symptoms.

Genetics
No specific genes have been identified in DLB.

Neuroimaging
 Atrophy in dorsal midbrain, striatum, and hypothalamus

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