Lecture 11-14: nutrition for the ageing brain

Question 1

 Total brain volume decreases upon ageing (from age of 30, each decade = 2-3% reduction in brain weight) in both grey + white matter
True/false

Answer 1

true. Mostly prefrontal cortex & hippocampus

Question 2

• Volume decrease partly due to ..

Answer 2

Changes in neurons:
- neuronal size
- no of synapses
- loss of myelin sheets

Question 3

What two things also happen with an ageing brain?

Answer 3

 White matter hyperintensities
 Neurotransmitters
- Change in two ways: altered production & receptors (decline or upregulated)
- Dopamine and serotonin most affected by ageing, alongside profound changes in acetylcholine (Ach) production.

Question 4

Protein aggregation happens upon ageing. This is always via differnt mechanisms
true/false

Answer 4

true

Question 5

What are sirtuins?

Answer 5

Class of NAD+-dependent signalling proteins involved in metabolic regulation (they can silence genes)

• Sensors amounts of energy, day light, stress ~ cellular distress
• Promote cell survival and health
• Play a critical part in ageing/longevity = neurodegeneration

Question 6

Inflammageing leads to activation of X in the brain

Answer 6

microglia

Question 7

 When we age, there is always more activation of microglia. What do they do?

Answer 7

They support the neurons and form myelin around the neurons. They also serve a immunological function.

Question 8

 When we age, there is more production of pro-inflammatory, instead of anti-inflammatory cytokines (inflammageing)
 In brain: this leads to more

Answer 8

reactivation of the microglias (=marker)

Question 9

X = Collective term of all degenerated protein/lipid/nucleic molecules, damaged bc of anchored sugar molecules

Answer 9

AGEs: Advanced Glycation End products

Question 10

By what reaction are AGEs formed?

Answer 10

maillard reaction (sugar attaching to protein. Hours/days) in your body – long lived, irreversibly formed.

Question 11

 AGEs bind to receptors (RAGEs) (also in brain). This increases

Answer 11

an inflammatory response

Question 12

What two types of intelligence are there

Answer 12

Fluid (novel-processing), Crystallized (Learned – knowledge)

Question 13

What happens to these types of intelligences upon ageing?

Answer 13

crystallized: increases
Fluid: decreases

Question 14

What is ‘successful’brain ageing?

Answer 14

 Successful: ‘brain reserve’ (structure: you were born with a particular size. Changes up to 18, also education plays a role here) + ‘cognitive reserve’ (relate to circuitry in brain: ways to get jobs done, synaptic connections)

Question 15

X explains the difference in neuropathology upon ageing

Answer 15

High vs low brain reserve (you were born with a particular size)

Question 16

What other dementias are there besides alzheimers?

Answer 16

vascular dementia
lewy body dementia
frontotemporal dementia
other

Question 17

MCI = mild cognitive impairment
Another form of cognitive impairmnet: effect can maybe be reversed. What is it called?

Answer 17

SCD = Subjective clinical decline.

Question 18

It is possible that some persons with the same amount of protein aggregates develop alzheimer’s and some don’t.
true/false

Answer 18

true

Question 19

symptoms of MCI?

Answer 19

cognitive changes of concern to individual and family
one or more cognitive domains impaired significantly
preserved activities of daily living

Question 20

Normal ageing = Neuronal loss only in X.
Few tangles is normal/not normal

Answer 20

hippocampus
Normal

Question 21

Alzheimers disease is characterized by

Answer 21

Protein aggregation:
= amyloid-beta & tau
Formation of plaques & tangles
Neuronal death

Question 22

 Taking out amyloid-beta will decrease disease symptoms

true/false

Answer 22

false

Question 23

Risk factors for abnormal brain ageing + %s?

Answer 23

 Non-modifiable risk factors (60%)
- Genes
- Age
 Modifiable risk factors (40%)
- Dietary components -> indirect
Alcohol intake, Obesity, Diabetes, Hypertension
 Lifestyle-related factors (18-20%)
- Not a one-on-one relationship (more sports = maybe change in diet)

Question 24

What is an important genetic risk factor for AD? What is it?

Answer 24

ApoE: Apolipoprotein E
 Plays a role in the transport of fat & cholesterol in brain

Question 25

Three variants of ApoE?

Answer 25

• e2: protective (epsilon)
• e3: neutral
• e4: increases (+29%) wit one allele

Question 26

Why is e4 allele increasing the risk of alzheimers?

Answer 26

e4: shift towards use of omega-3-fatty acids as brain fuel

exact mechanism unknown

Question 27

Q: “AGEs (advanced glycation end product) are irreversibly formed. Which statements below about “AGEs” are true?
A: (1) AGEs are formed via the Maillard reaction
(2) They can be formed both endogenously and exogenously
(3)AGEs are not harmful
(4) AGEs are in fact the covalent attachment of a sugar to a protein

Answer 27

1, 2, 4

Question 28

Q: “When does age-related cognitive decline begin?”

Answer 28

A: “From the age of 20-30”

Question 29

 B-vitamins: B6, B12 + folate, why are they important in healthy brain ageing?

Answer 29

They regulate the homocysteine metabolism.
B6 is needed to convert homocysteine into cysteine.
B12+folate also play a role.

Homocysteine = risk factor alzheimers disease. > One of metabolites (cysteine) destroys neurons (in rats).

Question 30

In what food sources can you find B6, B12, folate?

Answer 30

B6: wholegrains, nuts, seeds, animal products
B12: animal products (liver), dairy (fortified)
Folate: Leafy veg, animal products

Question 31

What are possible explanations for mixed results of vit B +cognitive decline in RCT’s ?

Answer 31

• Study population (baseline level, cognitive state)
• Beneficial (interactive) effects of B-vitamins on other nutrients (omega-3-fatty acids: when levels are too low, vit D does not work. So, a lot of interactive effects)

Question 32

What nutrients are needed to make serotonine?

Answer 32

1. B6, B3, zinc, folate, magnesium (tryptophan
   -> 5HTP)
2. B6, C, zinc, folate, magnesium (5HTP-> serotonine)

Question 33

What nutrients are needed to make dopamine/noradrenaline?

Answer 33

1. B6, folate, iron (Tyrosine -> L-dopa)
2. B6, magnesium (L-dopa-> dopamine)
3. C, copper (dopamine ->noradrenaline)

Question 34

What nutrients are needed for high amount of anti-oxidants?

Answer 34

carotenoids/vit C/vit E/trace elements/flavonoids/polyphenols

Question 35

Vit d + brain = unclear proof, only observational. What are the guidelines?

Answer 35

women 50-69: 10 microgr/day + women and men with medium skin tone

20 microgr/day for men and women 70 or older

Question 36

What form of vit D is measured in the blood?

Answer 36

Calcidiol

Question 37

In kidneys, calcidiol is transformed into..

Answer 37

calcitriol (25(OH)D3): active metabolite binding to receptors

Question 38

Q: “Which statement is false?”
A: (1) B-vitamins are necessary for homocysteine metabolism, the latter which is considered a risk measure in plasma for dementia
(2) An optimal omega-3-status is necessary in order for vit-B supplements to work properly
(3) B-vitamins are not important as cofactors for neurotransmitter synthesis (eg serotonin/dopamine)

Answer 38

(3) B-vitamins are not important as cofactors for neurotransmitter synthesis (eg serotonin/dopamine)

Question 39

Q: “Which of these statements is true?”
A: (1) “Vit D needs to be supplemented (10 microgr/day) to older aults from the age of 70 onwards, irrespective of gender, including individuals with a medium skin tone
(2) Vit D needs to be supplemented to all women between 60-69 (10 mirogr) and to both men and women from the age of 70 onwards (20 microgr) all of this includes men with medium skin tone, living far away from the equator
(3) Vit D needs to be supplemented to males from the age of 60 onwards, only in Caucasian individuals

Answer 39

(2) Vit D needs to be supplemented to all women between 60-69 (10 mirogr) and to both men and women from the age of 70 onwards (20 microgr) all of this includes men with medium skin tone, living far away from the equator