Dementia Neurobiology

Question 1

In order to diagnose dementia you need?

Answer 1

6 months of memory decline or other cognitive abilities

And progressive character

Question 2

What percent of dementia is Alzheimer’s?

Answer 2

50-60%

Question 3

What are the changes in dementia?

Answer 3

Intra neuronal inclusion bodies, lewy and picks
Extra neuronal inclusion bodies e.g amyloid beta plaques/ tau
Atrophy brain region

Enlarged ventricles

Question 4

Misfolding of protein in brain?

Answer 4

B amyloid

Question 5

Abnormal accumulation that is due to?

Answer 5

Tau

Question 6

Amyloid precursor protein to plaque generation?

Answer 6

If done by the beta secretase then gamma secretase which will give you AB peptide, forming a plaque

Question 7

Paired helical filaments are made of?

Answer 7

Phosphorylated tau

Question 8

Tau is normally important for?

Answer 8

Stabilising Microtubules

Question 9

Braak and braak staging?

Answer 9

Transentorhinal 1 and 2
Limbic 3 and 4
Isocortical 5 and 6

Question 10

Which neurons and where are they atrophied in AD?

Answer 10

Cholinergic neurons in nucleus basalis

Question 11

Risk factors for Alzheimer’s?

Answer 11

Age
Vascular risk factors
Lack of exercise 
Low level of education
Diet
Family history
Genetic

Question 12

What is atypical presentation of AD?

Answer 12

Posterior cortical atrophy
Logopenic aphasia
Behavioural frontal AD

Question 13

Lewy body dementia contains 2 types?

Answer 13

Dementia with a Lewy bodies

Parkinson’s disease dementia

Question 14

How common is LBD?

Answer 14

2nd most common with 23% of people

Question 15

Lewy bodies are found where?

Answer 15

Dopaminergic neurons of substantia nigra in about 90% of patients with PD

Question 16

What are Lewy bodies made of?

Answer 16

Alpha synuclein

Question 17

Where is alpha synuclein normally found?

Answer 17

In cytosolic and mitochondria, mostly in neuronal cells some glial

Question 18

Why is alpha synuclein important?

Answer 18

Interaction with microtubule network

Involved in synaptic vesicle formation

Catecholamine metabolism in DA ergic neurons

Ca homeostasis

Question 19

What is alpha synuclein encoded by?

Answer 19

SNCA gene in 3 splicing isoforms

Question 20

What is the staging of PD alpha synuclein

Answer 20

1. Autonomic and olfactory disturbances
2. Sleep and motor disturbances
3. Emotional and cognitive disturbances

Question 21

CLINICAL PRESENTATION OF DLB?

Answer 21

Essential feature - dementia defined as progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function or with usual daily activities.
• Disproportionate attentional, executive and visual processing deficits relative to memory and naming.
• Fluctuating cognition with pronounced variations in attention, alertness and arousal
• Recurrent visual hallucinations, typically well formed and detailed
• REM sleep behaviour disorder
• Spontaneous features of parkinsonisM

Question 22

Frontotemporal lobar degeneration?

Answer 22

Classical syndromes:
Semantic dementia
Progressive non-affluent aphasia
Behavioural variant FTD

Motor disorders:
Parkinsonian syndromes
Motor neuron disease

Question 23

What is the second most common neurodegenerative dementia after AD in people under 65?

Answer 23

FTLD

Question 24

Pathologies in TFLD?

Answer 24

Atrophy of frontal and temporal lobes

Tau, TDP43 and FUS

Question 25

Vascular dementia is not…?

Answer 25

Neurodegenerative dementia

Question 26

What can vascular dementia be due to?

Answer 26

Ischaemia or haemorrhagic brain damage

Question 27

Common mechanisms causing vascular dementia?

Answer 27

Single strategically placed infarcts Multiple cortical infarcts Subcortical small vessel disease

Question 28

Huntington’s disease due to?

Answer 28

Autosomal dominant mutation in Huntington gene on chromosome 4, chroea, cognitive and behavioural symptoms neuropsychiatric syndrome includes anxiety and depression, apathy, irritability, disinhibition, psychosis, compulsive behaviou

Question 29

Cognitive impairment in HIV?

Answer 29

Rare with antiretroviral treatment 2%

Question 30

A prion can?

Answer 30

Adopt 2 conformational states, one of which is self-perpetuating

Question 31

Prions account for what percent of creutzfeldt Jakob disease?

Answer 31

85

Question 32

Incidence of CJD?

Answer 32

1 per million

Question 33

Prion disorder due to varian CHD is caused by?

Answer 33

Eating BSE or blood transfusion

Question 34

People with prion disease, variant cjd show?

Answer 34

Pulvinar sign- hyperintensity of pulvinar nuclei Painful paraesthesisas Psychiatric prodrome

Question 35

Recent licensing for dementia drug?

Answer 35

Aducanumab