Dementia + role nutrition 1

Question 1

Most people with dementia live in..

Answer 1

Asia

Question 2

Dementia has the highest burden of disease, true/false?

Answer 2

True

Question 3

Where does AD begin? What is the prevalence?

Answer 3

Hippocampus
60-70%

Question 4

How long do people with AD live, on average?

Answer 4

• 7-9 years of disease

Question 5

How does the disease progress (symptoms)?

Answer 5

• Early symptoms: memory complaints
• Later symptoms: disorientation, mood and behaviour changes, confusion, suspicions
• Eventually: basic functions such as speaking, walking and swallowing impaired, ultimately fatal

Question 6

What are the four main groups of dementia?

Answer 6

AD
Vascular dementia
Dementia with lewy bodies
Frontotemporal dementia

Question 7

Vascular dementia: prevalence, brain damage, first symptoms?

Answer 7

15-20%
Large/small infarcts (white matter lesions)
Slowness, reduction in executive functions

Question 8

What type of brain damage happens with AD?

Answer 8

Amyloid plaques, tau tangles, brain shrinkage

Question 9

Lewy body dementia: prevalence, brain damage, first symptoms?

Answer 9

15%
Lewy bodies of alpha-synuclein
Visual hallucinations, parkinsonism, fluctuating course

Question 10

Frontotemporal dementia: prevalence, brain damage, first symptoms?

Answer 10

5%
Frontal and temporal lobes damage
▪ Frontal lobes: control behaviour and emotions
▪ Temporal lobes (on either side of the brain): language problems

Behavioural and personality changes, language problems

Question 11

What % fails the drug trials?

Answer 11

99.6%

Question 12

Why is finding a treatment so difficult for dementia?

Answer 12

• BBB
• Side effects
• Exact underlying mechanism(s) unclear + heterogeneous

Question 13

What two symptom-reducing drugs are mainly used?

Answer 13

 Cholinesterase inhibitors
 NMDA receptor antagonists

Question 14

What do NMDA receptor antagonists do? In what time frame of disease?

Answer 14

Via glutamate (AD: too much glutamate -> damage to nerves)
Moderate-late AD

Question 15

What do cholesterase inhibitors do? When are they used in disease?

Answer 15

Prevent breakdown Ach (AD: lower levels)
Mild-moderate AD

Question 16

What do these drugs that alter disease progression: Aducanumad + lecanemab, do?

Answer 16

▪ No cure, but changes the underlying biology (amyloid-β)
▪ Both monoclonal antibodies
▪ Main difference: mechanism of action
- Aducanumab: removes beta-amyloid
- Lecanemab: blocks formation of amyloid

Question 17

Aducanumad + lecanemab: why not approved in europe?

Answer 17

Major side effects, limited effects on cognition
▪ More research is needed!

Question 18

What are non-modifiable risk factors with dementia?

Answer 18

• Age (doubles with every 5 year increase in age): most important risk factor
• Genes

Question 19

What is the difference between risk factors in early and late onset dementia?

Answer 19

Early:

APP protein
PS1, PS2 proteins
Increased amyloid beta proteins
Rare, 5% of cases

Late:

ApoE gene
ApoE 4: 2 alleles = greatest risk, dose-related
ApoE 2: protective
Amyloid breakdown, transport fat cholesterol
(age the largest risk factor, of course)

Question 20

What do centenarians without AD have in common?

Answer 20

rare genetic variant in the PLCG2 gene, which has a role in immune system signalling