w5: : Parkinson’s Disease Dementia, Dementia with Lewy bodies, and Huntington’s Disease

Question 1

Parkinson’s Disease Dementia, Dementia with Lewy bodies, and Huntington’s Disease

Answer 1

• All associated with frontal striatal network
• All related via the dopaminergic pathway – all involve this
• Subcortical dementia – limited sight, but originate in subcortical area
• All have prominent motor system’s – in contrast with Alzheimer’s, frontal dementia and all

Question 2

Lewy Body Diseases

Answer 2

we find lewy bodies within the brain

**lewy body diseases **= parkinsons, parkinsons w dementia, dementia with lewy bodies.

lewy body dementias: parkinson’s w dementia, dementia w lewy bodies.

Question 3

Lewy Bodies

Answer 3

Neuronal inclusions:
- Protein: ubiquitin and alpha-synuclein
Typically found in all subcortical nuclei
- Substantia nigra
Regional distribution can vary between people with lewy body disease
- Correlating with the symptomatology

Pathology differs strongly from the pathology of Alzheimer’s disease.

Question 4

Lewy Body Disease

Parkinson’s disease

Answer 4

First described by James Parkinsons in 1817
- A disease of the central nervous system

• Progressive, neurodegenerative disease
• Caused by death of dopaminergic neurons in the substantia nigra.

results in movement disorder, PET scan for diagnosis

• The striatum is involved.
• Subcortical area
• Connected to frontal cortex- important for both movement and cognitive functioning.

Question 5

Parkinson’s summed yp

Answer 5

• The cells in the substantia nigra degenerate
• Consequence: a decreased amount of dopamine
• Results: dysfunction striatum
• Dysfunction of the areas connected to the striatum
• Whole network starts to not work

Question 6

Parkinson’s Clinical Presentation

Answer 6

Motor symptoms
- Tremor- rest tremor, in hands, legs. Person is sitting and having a tremor. Not present in action typically
- Rigidity – can only feel, resistance in the limb
- Bradykinesia- slowness of movement
- Postural instability- people are easily out of balance
^^ at least 2 of these have to be present to diagnose

Clinical appearance
- Difficulties doing things we do automatically !!
Ie.
Walking
Rising from a chair
Tunring around in bed
Keeping balance
Monotone speech
Drooling

^^cannot control automatic motor movements and control

Question 7

Parkinson’s Neuropsychiatric symptoms

Answer 7

depression
apathy
anhedonis
visual hallucinations- later stages
impulse dusorders - due to medication
- Dopamine also important for reward system, too much can cause impulse disorders- ie. Gambling, too much eating

Question 8

Parkinson’s + Cognitive Impariments

Answer 8

24% of ppl w Parkinsons already have cognitive impairment
- MCI w parkinsons.
- parkinsons w dementia

• Progress over time
• If they progress then could get mild cognitive impairment In context of parkinsons
• And if it progress even more = parkinsons dementia
• Information is processed slower, slower thinking = psychomotor symptoms
• Language = not aphasia! Complex sentences might be difficult to understand or speak
• Memory

main issues:
psychomotor speed
visuospatial skills
attention and executive functions

affected but less so:
- language
- memory

issues with attention and executive function due to striatum being involved–> connected to frontal cortex

Question 9

Lewy Body Dementia

Parkinson’s dementia- Dementia

Answer 9

• 50% of people with parkinsons develop parkinsons dementia
• People with parkinsons mainly shor degeneration of attention and psychomotor speed

Risk factors of dementia:
- Higher age
- Visuoconstructive dysfunctions
- Hallucinations visual
- Impaired semantic verbal fluence – name as many animals as possible in one minute

Question 10

Parkinson’s Disease Dementia- diagnostic criteria

Answer 10

A. the disturbance occurs in setting of established parkinsons
B. there is insidious onset and gradual progression of cognitive impairments
C. disorder not attributable to toher medical condition/ medicine
D. impairments have negative influence on functioning
E. impairments are present in at least two of the following:
- memory
- attention
- executive function
- visuospatial functions

the presence of one of the following behavioural disorders makes diagnosis more likely
- visual hallucinatios
- agitation
- excessive daytime sleepiness
- depression
- anxiety
- apathy

Question 11

Dementia with Lewy Bodies

Answer 11

Pathological Cause and Progression

Key Feature: Early accumulation of Lewy bodies in cortical areas​
.
Progression: Cognitive decline appears first, with motor symptoms developing later​

Question 12

Onset and Symtoms DLB

Answer 12

Onset: Cognitive symptoms precede or occur within 12 months of motor symptoms​
.
Symptoms:
Fluctuations in attention/alertness.
Vivid visual hallucinations.
REM sleep behaviour disorder.
Parkinsonism

Question 13

Dementia w Lewy Bodies DSM-5

Answer 13

A. criteria met for major or mild neurocognitive disorder

B. disorder has insisius onset + gredual progression

B. meets combination of core diagnostic features and suggestive features for lewy bodies disoder.

C. not better explained by something else

core symptoms:
- fluctuating allertness/attention
- vivid hallucinations
- parkinsoniskm- onset subsequent cognitive decline

suggestive symptoms:
REM sleep disorder
neuroleptic sensitivity

Question 14

Central Features DLB

Answer 14

progressive cognitive decline that interferes w normal functioning

impairments in:
- memory - not as bad as alzh
- visuospatial functions
- executive functions
- attention

differentiation from alzh
more severe effects in:
- attention
- verbal fluency
- visuospatial ability
- executive functions
- psychomotor speed
^^ all relate to frontal cortex functions

**mini mental state exam ** NOT valid for lewy bodies- too fosued on memory

Question 15

PDD vs Alzh

Answer 15

• More cortical disorders, such as aphasia, apraxiam agnosia are not common in people with parkinsons disease dementia
• People with parkinsons disease dementia mainly have impairments in retrieving information from memory – recognising is intact, extrernal cues have a positive effect.

Visuospatial impairments are more often present in people with parkinsons dementia- perceiving the world around you, how objects related to each other, identifying objects

Little cortical atrophy (what happens in alzh)
More fronto-parietal hypometabolism

Question 16

Alzh vs DLB

Answer 16

memory issues aren’t as pronounced as Alzh.

mini mental health examination not sensitive for DLB - too memory focused

in DLB- memory fails at retrieval stage compared to failure of storage in alzh
- intact performance on recognition tasks

rate of progression slightly fasterin ppl w DLB compared to alzh.

DLB- prominent visuospatial dysfunction, seen in copy drawring tasks, ie. of a clock

Question 17

Core + Suggestive Features DLB

fluctuations cognition, parkinsonism, neuropsychiatric, REM

Answer 17

Core features: Fluctuation in cognition + allertness
- prominent symptom
- can occur rapifly or over weeks
- difficult to indentify due to range in fluctuations
- use same test twice during assessment- compare if significant difference in scores b/w

core feature: parkinsonism
- motor symptoms
- 45-100% w DLB have it
- mirror parkinsons
- rest tremor less prominent
- ridgidity and bradykinesia is present in both
-Postural stability, hypomimia and gait difficulties - more in DLB
AFTER cognitive symptoms

core feature: neuropsychiatric
- 80% have hallucinations
- occur early typically
- vivid, colourful, often not scary- don’t realise its not real
- apathy, anxiety, depression, MAINLY visual hallucinations

Suggestive: REM disorder
- normal atonia of REM does not occur
- result: movement, vigorous, during REM - as if acting out dream
- REM sleep disorder is typical of DLB
- REM disorder can occur before dementia- risk factor

suggestive: severe neuroleptic sensitivity
- neuroleptics are prescribed to treat psychoses (clozapie or haldol)
- side effects of neuroleptics: drowsiness, parkinsonism, falls)

side effects can occur to any person w dementia but are more prominent in peorple with a dementia w lewy bodies

Question 18

DLB vs PDD

Answer 18

reduced dopaminergic transmission: no difference b/w PDD and DLB

DLB, PDD- strong overlap in regard to
- pathology
- symptoms

particular apparent in later stages - bc in later stages both have cogntiive impariemnts and parkinsonism

DLB + PDD = descriptive labels for the course of symptoms

Question 19

Hungtington’s Disease

Answer 19

progressive, hreditary disease w insidious onset.

characterised by:
- motor symptoms
- cognitive impairments
- neuropsychiatric symptoms
^^ may lead to dementia

Question 20

Genetic Basis Huntington

Answer 20

1993: Huntington caused by CAG repeat on short arm chromosome 4

healthy: <36 repeats
36-39 repeats- mild symptoms can remain healthy until old age
40+ : indiv develops hungtington

autosomal dominant disease

Question 21

Pathology Huntington:

Answer 21

Huntington gene –> changed function of huntingtine protein = degeneration certain parts of brain

early stages: degeneration of striatum = dysfunction of fronto-striatal circuits

–> changes dopaminergic transmission systems (decreased receptor binding)

Late stages of disease: global atrophy of brain

not strictcly movement disorder, has cogntive decline too

Question 22

Hungtington Motor Symptoms

Answer 22

Dysikinesias
-** chorea**- increase in random movements, uncontrolled
- hypokinesia- decrease number spontaneous movements

bradykinesia- slowness of movement
dystonia- sustained muscle contractions
ridgidity
dysarthria
problems with eye movements
problems with swallowing
problems with keeping balance

chorea most striking symptom

Question 23

Hungtington cognitive symptoms

Answer 23

progressive decline cognitive functioning differst b/w ppl.
- relatively mild until later
OR
- fast progression, dementia early

Impairments particularly present:
- psychomotor speed
- executive functions
- attention
- memory - in retrieval

Question 24

Hungtington - Memory dysf

Answer 24

impairments in:
- encoding and retrival of information - recongition and kowledge of general facts are relativelly intact

working memory

• early stages memory impairments can be due to executive function and attention impairments

Question 25

Hunginton - Psychomotor speed

Answer 25

slowness of thinking- bradyphrenia

slowness in acting

slowness is not caused by motor symptoms

Question 26

Hungtington cogntition-
close to onset, late stages

Answer 26

close to onset: impairments in memory, executive functions, attention, psychomotor speed are prsent in some but NOT ALL

early and later stages: majority pf ppl show impairments in memory, executive functions, attention, and psychomotor speed

Question 27

Hungtington disease insight

Answer 27

ppl w Hungtington rarely compain about motor symptoms + cogntive impairments.

due to:
- lack of insight as a consequence of cognitive dysfunction
- psychological protection mechanism

Question 28

Hungtington- Neuropsychiatry

Answer 28

large indiv differences.

affective disorders:
- depression- consequence of pathophysiological changes
- anxiety- insecure ab future
- apathy- middle/ late stages of disease
- agitation- one of first symptoms
- disinhibition- no self control related to eating, drinking, speaking or sexuality
- compulsive behaviour- obsessive and compulsive thoughts or acts
- psychoses- hallucinations or delusions

Question 29

Hungtington Summary

Answer 29

progressive, hereditary disease w insidious onset
- CAG repeat on chromosome 4

characterised by degeneration of the striatum and dysfunction of fronto-striatal circuits

Question 30

Treatments/ Interventions Hungtington

Answer 30

Pharmacological Treatments
1. Tetrabenazine:
o Reduces chorea (involuntary movements).
o Side Effect: May increase depression risk.
2. SSRIs:
o Effective for managing irritability and depressive symptoms.

Non-Pharmacological Interventions
1. Assistive Technology for Cognition (ATC):
o Tools (e.g., planners, memory aids) to address cognitive inefficiencies.
o Mixed evidence for improving quality of life.
2. Cognitive and Physical Interventions:
o Rhythm exercises: Improve executive functions and white matter integrity.
o Multidisciplinary programs: Combine physical and cognitive exercises to enhance brain volume and verbal learning.
o Need for randomized controlled trials (RCTs) to confirm efficacy.
3. Behavioral Interventions:
o Encourage participation in structured, pleasurable activities.
o Manage irritability through identifying triggers and educating caregivers.