LBD & PDD

Question 1

Lewy Body Dementia

Answer 1

Lewy bodies are caused by abnormal aggregation of protein a-synuclein

this neuropathology is also visible in Parkinson’s and MSA, lot of overlap between them

Question 2

Etiology

Answer 2

First described in 1961

Prev:
- After AD, second most common neurodegenerative disease (VaD is not neurodegenerative)
- 3rd most common overall
- Estimates of prev vary widely, most recent; 4-7% of dementia cases

• Often after 65, early is rare
• More in men than in women
• Mean survival time is roughly 4 yrs after diagnosis

Question 3

Risk factors

Answer 3

Age
Male sex
Prior diagnosis of depression or anxiety
Family history of PD

Question 4

PD

Answer 4

2nd most common neurodegenerative disease
- Early onset rare

At time of diagnosis, +/- 30% have MCI as well, after 3 years this is 55%
- Pattern of cogn. impairment is heterogeneous
- Multiple domain MCI more common than single
- 10% develops PDD after 1 yr, 50% after 5

PD dementia (PDD)
- Risk increased in longer survival rate; up to 80% have dementia after 20 yrs diagnosis

Question 5

PDD + risk factors

Answer 5

Extensive overlap between PDD and LBD in both symptoms and neuropathology

Distinguished by looking at onset of dementia in relation to motor symptoms;
- Diagnosis DLB: dementia symptoms precede/within 12 months onset motor signs
- Diagnosis PDD: dementia symptoms > 12 months after onset motor signs

Both types referred to as “Lewy body disease”

Risk factors
age
Male
smoking
Severe PD symptoms
Hallucination
REM sleep behaviour disorder
Hypertension

Higher education is protective factor.

Question 6

Neuropathology

Answer 6

DLB
- Lewy bodies primarily exist in the cortex

PDD
- Lewy bodies primarily exist in substantia nigra

Progression in Braak stages;
1-2. LB in olfactory, brain stem regions
- autonomic and olfactory disturbance

3-4. LB in midbrain, substantia nigra (diagnosis)
- Sleep and motor disturbance

5-6. LB in cortical areas across most of neocortex
- Emotional and cognitive disturbance

Question 7

Cholinergic neurons

Answer 7

Nerve cells that use acetylcholine (ACh) as primary neurotransmitter, particularly in areas of the brain involved in memory, attention, and learning.

Cholinergic neurons are crucial for:
- Attention and alertness
- Learning and memory
- Regulation of REM sleep
- Motor control

Question 8

choline depletion

Answer 8

Due to loss of cholinergic neurons, the level of choline is reduced (nutrient used to make ACh), thus less ACh is produced.

This is especially in DLB, where this deficiency occurs in early stages of the disease.
- Contributes to early symptoms eg reduced alertness and hallucinations

Question 9

Acetylcholinesterase

Answer 9

Acetylcholinesterase inhibitors are drugs that prevent the breakdown of acetylcholine, increasing its levels in the brain.
- used as medication, can have positive effect on symptoms