Nutrition and cognitive development in later life

Question 1

Dementia - A definition…

Answer 1

‘Dementia is a clinical syndrome characterised by multiple cognitive deficits severe enough to interfere with daily functioning, including social and professional activities’ (Fratiglioni et al., 2010).

Not a specific definition………more broad
An umbrella term for a group of symptoms

Question 2

Mild Cognitive Impairment (MCI)

Answer 2

Some people have problems with their memory or thinking but these are not bad enough to affect their everyday life.

A doctor may diagnose them with mild cognitive impairment (MCI).

This is not a type of dementia, but research shows that people with MCI have an increased risk of going on to develop dementia.

MCI can also be caused by other conditions such as anxiety, depression, physical illness and the side effects of medication.

Some people with MCI do not go on to develop dementia, and a small number of people will even get better.

Question 3

Who gets dementia?

Answer 3

The prevalence of dementia in 65+ year olds is 7.1% (based on 2013 population data)

• Approaching 1 million people with dementia in the UK
• This equals one in every 79 (1.3%) of the entire UK population, and 1 in every 14 of the population aged 65 years and over

Among people with late-onset dementia:

• 55.4% have mild dementia
• 32.1% have moderate dementia
• 12.5% have severe dementia

Question 4

Dementia in the future…

Answer 4

The total number of people with dementia in the UK is forecast to increase to over 1 million by 2025 and over 2 million by 2051

Question 5

Economic cost of dementia…

Answer 5

The overall economic impact of dementia in the UK is £26.3 billion, working out at an average annual cost of £32,250 per person.
£4.3 billion is spent on direct healthcare costs
£10.3 billion is spent on social care for people with dementia in the UK.

Question 6

What causes Dementia?

Answer 6

Alzheimer’s disease – This is the most common cause of dementia. In Alzheimer’s disease, an abnormal protein surrounds brain cells and another protein damages their internal structure. In time, chemical connections between brain cells are lost and cells begin to die.

Question 7

Symptoms of Dementia (Alzheimer’s Society, 2019)

Answer 7

day-to-day memory

concentrating, planning, organising

language

visuopatial skills - judging distence

orientation

Question 8

Pathology of Alzheimer’s Disease: The Healthy Neuron

Answer 8

Signal comes to dendrite and goes along, left to right

dendrite
axon
myelin sheeth
node of ranvier
axon terminal

Question 9

Pathology of Alzheimer’s disease

Answer 9

In Alzheimer’s disease, however, many neurons stop functioning, lose connections with other neurons, and die.

Alzheimer’s disrupts processes vital to neurons and their networks, including communication, metabolism, and repair.

Question 10

Characteristics of Alzheimer’s disease with neurons

Answer 10

1) Amyloid plaques
Found in the spaces between neurons

Consist predominantly of abnormal deposits of a protein fragment called beta-amyloid.

Beta-amyloid is formed from the breakdown of a larger protein called amyloid precursor protein (APP).

Beta-amyloid 42, has a strong tendency to clump together.

When produced in excess, beta-amyloid 42 accumulates into plaques.

It is not yet determined if plaques are a cause or a by-product of Alzheimer’s disease.

2) Neurofibrillary tangles
Found inside neurons, neurofibrillary tangles are abnormal clumps of a protein called tau.

Healthy neurons are internally supported in part by structures called microtubules, which help guide nutrients and molecules from the cell body to the axon and dendrites.

Tau normally binds to and stabilizes microtubules.

In Alzheimer’s disease, however, tau undergoes abnormal chemical changes that cause it to detach from microtubules and stick to other tau molecules

This forms threads that eventually clump together to form tangles.

The tangles disrupt the microtubule network and create blocks in the neuron’s transport system.

Abnormal tau may also cause blocks in synaptic signalling.

3) Loss of neuronal Connections and cell death
In Alzheimer’s disease, the synaptic connections between certain groups of neurons stop functioning and begin to degenerate.

This degeneration may be due to the abnormal deposits of beta-amyloid and tau.

When neurons lose their connections, they cannot function properly and eventually die.

As neuronal injury and death spread through the brain, connections between networks of neurons break down, and affected regions begin to shrink in a process called brain atrophy.

By the final stage of Alzheimer’s, damage is widespread, and brain tissue has shrunk significantly.

Question 11

Risk Factors for AD: Non-modifiable

Answer 11

Ageing
- Higher blood pressure + increased risk of cardiovascular diseases
- Changes to nerve cells, DNA and cell structure + the weakening of the body’s natural repair systems
- Loss of sex hormones after mid-life changes

Sex
- The reasons for this are still unclear
- It has been suggested that Alzheimer’s disease in women is linked to a lack of the hormone oestrogen after the menopause
- However, controlled trials of hormone replacement therapy (HRT, which replaces female hormones) have not been shown to reduce the risk of developing Alzheimer’s

Genetic Susceptibility
- For example, inheriting certain versions (variants) of the gene apolipoprotein E (APOE) increases a person’s risk of developing Alzheimer’s disease.
- Having a close relative (parent or sibling) with Alzheimer’s disease increases your own chances of developing the disease very slightly compared to someone with no family history.

Question 12

Genetic Susceptibility: Early Onset AD

Answer 12

This form of Alzheimer’s tends to cluster within families, sometimes with several generations affected, in which case it is called familial disease.

In some of these cases, early onset Alzheimer’s is caused by mutations in one of three genes.

amyloid precursor protein gene (APP)
two presenilin genes (PSEN-1 and PSEN-2).

People with any of these extremely rare mutations tend to develop Alzheimer’s disease in their 30s or 40s.

On average, half of the children of a person with one of these rare genetic mutations will inherit the disease.

People who do not inherit the mutation cannot pass it on

Question 13

Genetic Susceptibility: APOE variants risk of developing AD

Answer 13

(APOE). Th APOE gene is found on chromosome 19 and comes in three forms, which by convention are named with the Greek letter epsilon (ε):
- APOE ε2- APOE ε3- APOE ε4.
APOE ε4 is associated with a higher risk of Alzheimer’s.
About a quarter of the general population inherits one copy of the APOE ε4 gene.
About 2 per cent of the population gets a ‘double dose’ of the APOE ε4 gene – one from each parent. This further increases lifetime risk of developing AD
The APOE ε2 form of the gene is mildly protective against Alzheimer’s: people with it are slightly less likely to develop the disease.

Question 14

Risk Factors: Modifiable

Answer 14

Physical activity
Cardiovascular factors (hypertension, diabetes, obesity)
Smoking
Depression
Excessive alcohol
Traumatic brain injury
Diet

Question 15

Diet and Alzheimer’s Disease

Answer 15

Omega-3 fatty acids

Fruit and vegetable consumption

Mediterranean dietary patterns

Dietary intake of antioxidants (vitamin E, vitamin C, carotenoids, flavonoids, polyphenols)

Question 16

Antioxidants and AD risk
Potential mechanisms

Answer 16

The brain is vulnerable to oxidative damage – an imbalance between the production of reactive oxygen species and the efficiency of antioxidant defence systems.
Chronic accumulation of reactive oxygen species in the brain may exhaust antioxidant capacity, including antioxidant vitamins, and lead to onset of AD.
Uses approx. 20% of respired oxygen but has relatively low levels of antioxidant defence mechanisms.
Brain is therefore particularly vulnerable to free radical damage.
‘Increased levels of lipid peroxidation, hydrogen peroxide and nitrogen oxidative species and decreased total antioxidant capacity have been reported in AD patients’ (Otaegui-Arrazole et al., 2014).

Question 17

Dietary antioxidants and Alzheimer’s Disease

Answer 17

Various research has suggested that dietary intakes of the following have been associated with a reduced risk of dementia and/or AD:

Vitamin E (Englehart et al., 2005; Morris et al., 2005; Devore et al., 2010);

Vitamin C (Engelhart et al., 2002)

Flavonoids (Commenges et al., 2000; Letenneur et al., 2007)

Beta-carotene (Engelhart et al., 2002)

Question 18

Antioxidant supplements and cognitive performance

The effect of antioxidants on cognitive performance/dementia risk

Answer 18

Men treated with 50mg Beta-carotene on alternate days for 18 years had significantly better cognitive performance vs. men on placebo. (Grodstein et al., 2007).

Use of self-supplemented vitamin E and C alone or in combination did not reduce risk of AD or dementia over 5.5year follow-up (Gray et al., 2007).

Question 19

Why might there be discrepancies in findings between studies?

Answer 19

Study design - Observational studies (association studies) vs. interventions

Population under study - AD patients vs. MCI vs. healthy participants?

Dietary assessment limitations - we are generally not very good at assessing nutritional intake in association studies (e.g. FFQ limitations, 24-hour recall, etc…)

Stage of disease - Mild vs. Moderate vs. Severe?

Assessment of cognitive function/decline – different ways used across different studies

Baseline nutrient status - are participants sufficient/deficient in other nutrients?

Interventions - Dose? Duration? single nutrient supplementation? Co-nutrient supplementation?

Question 20

Fruit and vegetable intake and AD

Answer 20

High vegetable (but not fruit) consumption associated with a slower rate of cognitive decline with older age (Morris et al., 2006).

High consumption of vegetables (but not fruits) associated with less cognitive decline among older women (Kang et al., 2005).

The risk of AD is substantially decreased with increasing frequency of intake of fruit and vegetable juice (Dai et al., 2006).

Need to think about more of a whole food approach rather than single foods

Question 21

Summary of Antioxidants and AD…

Answer 21

Antioxidants from dietary fruit and vegetables, but not from supplements, may play a role in delaying the onset of AD (Dai et al., 2006).

‘Antioxidant treatment/supplementation does not appear to influence cognitive function in AD or in healthy participants’ (Oteagui-Arrazole et al., 2014).

‘Available data do not seem to support the idea that long-term dietary antioxidant intake can reduce AD risk’ (Oteagui-Arrazole et al., 2014).

Question 22

Potential mechanisms: Omega-3

Answer 22

Omega-3 fatty acids essential for proper neuronal and brain function
Key membrane components
Modulate processes such as inflammation and amyloid processing

Omega-3 PUFAs protect against vascular disease
Potential for decrease number of infarcts or micro haemorrhages

Question 23

Why no link between Omega-3 and AD risk?

Answer 23

Food composition tables are often incomplete, and this would lead to an underestimation of the true long-chain omega-3 fatty acids intake

Dietary intake of long-chain omega-3 fatty acids may also be accompanied by the intake of other nutrients such as saturated fat, which may attenuate the associations between LC-omega-3 fatty acids and risk of dementia or AD

Question 24

benifits of fish

Answer 24

Fish is also a good source of other nutrients, such as vitamins, essential amino acids and trace elements, and these nutrients may also contribute to cognitive function improvement (not just omega-3 LC-PUFA’s)
A higher fish intake may simply be an indicator of a healthier dietary pattern or higher socioeconomic status, which themselves are associated with better cognitive performance

Question 25

Vitamin D & AD

Answer 25

Majority is obs in natural few RCT….not been that successful….

Question 26

Mediterranean Diet and AD

Answer 26

Recent meta-analyses (Sofi et al., 2010; Opie et al., 2013; Otaegui-Arrazola et al., 2014) indicate that adherence to Mediterranean eating habits may reduce the incidence of neurodegenerative diseases
Higher adherence to MedDiet is associated with a decreased risk of cognitive decline, MCI and AD.

Feart et al., (2009) found no association between higher adherence to Mediterranean diet and risk of dementia.

Question 27

The mediterranean diet

Answer 27

Dietary pattern most widely studied.

Characterised by:
a high intake of vegetables,
legumes,
cereals,
fruits and nuts,
a high intake of olive oil,
with low intake of saturated fatty acids and;
moderately high consumption of fish.