Ageing, Alzheimers, MS & Parkinsons Disease Flashcards

1
Q

What is hormesis?

A

A process in which exposure to a low level of stress or toxicity induces an adaptive beneficial effect in a cell or organism.

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2
Q

A little stress increases the lifespan (or “health span”). True or false.

A

True. It’s called hormesis

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3
Q

List 5 contributors to ageing at physiological and molecular level

A

Exposure to toxins
Inadequate exercise
Poor nutrition
High stress
Genetic susceptibility
Chronic inflammation
Gut dysbiosis

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4
Q

_____________ dysfunction is a cause of ageing and is linked to MS, Alzheimer’s and Parkinsons diseases

A

Mitochondrial dysfunction

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5
Q

What is inflammageing?

A

Chronic low-grade inflammation increases as we age. Inflammageing is the result of pathological stimulation of the innate immune system.

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6
Q

Alzheimers Disease is associated with inlammageing of the _______

A

Brain

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7
Q

Give 2 examples of things that could contribute to hormesis

A

Calorie restriction
Phytochemicals
Exercise
Cognitive stimulation
Intermittent cold and heat

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8
Q

How does a healthy body respond to mild stress?

A

By increasing production of endogenous antioxidants
By increasing cellular quality control mechanisms

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9
Q

List 3 endogenous anti-oxidants increasingly produced by the body during hormesis / as a result of mild stress.

A

Glutathione
Catalase
Superoxide dismutase
Phase II detox enzymes

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10
Q

_______ is a transcription factor that senses cellular stress, and then responds by up regulating genes relating to the production of endogenous antioxidants (glutathione, SOD, etc)

A

Nrf2

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11
Q

Which 2 anti-ageing proteins are triggered by calorie restriction and exercise?

A

AMPK
Sirtuins (SIRT 1-7)

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12
Q

During a period of low cellular energy, AMPK and sirloins initiate a process called ___________ (self eating)

A

Autophagy

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13
Q

Which 2 anti-ageing proteins trigger autophagy during periods of low cellular energy?

A

Sirtuins
AMPK

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14
Q

What is autophagy of mitochondria called?

A

Mitophagy

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15
Q

In which 2 pathologies is mitophagy defective, resulting in low brain energy?

A

Alzheimers
Parkinsons

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16
Q

List 3 of the 9 key signatures of ageing

A

Telomere shortening
Genome instability
Epigenetic alterations
Loss of protein regulation and disposal
Insulin resistance
Cell senescence (biological ageing)
Stem cell loss
Altered callular communication

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17
Q

Excess phase 1 detoxification is linked to ageing and cancer. True or false?

A

True

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18
Q

Why is excess Phase 1 detoxification linked to ageing and cancer?

A

Because Phase 1 transforms xenobiotics, hormones and drugs into REACTIVE INTERMEDIATES, which are harmful if Phase II can’t keep up.

Phase 1 detox is important, but not too quickly!

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19
Q

List 3 plant compounds that can slow down phase 1 metabolism, protecting against cancer.

A

Turmeric
Green tea
Quercetin
Resveratrol
Garlic
Ginger

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20
Q

Which phases of liver detoxification does hormesis support?

A

Phase II and III

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21
Q

Exercise induces levels of PGC1-alpha protein. But what does it do?

A

Enables the synthesis of brand new mitochondria, through mitochondrial biogenesis

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22
Q

Obese and insulin resistant individuals present with mitochondrial dysfunction and reduced biogenesis. True or false?

A

True

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23
Q

What health conditions are AGES associated with?

A

Cancer
Diabetes
Neurodegeneration
Accelerated ageing

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24
Q

Name the most common form of dementia (60-80% of all cases).

A

Alzheimers Disease

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25
Q

List 5 risk factors for dementia

A

Chronic / acute stress
PPI medication
Poor diet
Vit & mineral deficiencies
Smoking
Alcohol
Poor lifestyle
Vaccinations
Hypertension
Diabetes
Mental Inactivity
Obesity
Physical inactivity
Social isolation
Environmental toxins
APoE polymorphism
Mid-life depression

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26
Q

What is APoE?

A

Apolipoprotein E (ApoE) is a major cholesterol carrier that supports lipid transport and injury repair in the brain.

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27
Q

Which two proteins are correlated with Alzheimers Disease pathology?

A

Amyloid beta and tau

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28
Q

Name two brain-centred pathologies in which you might find Lewy bodies

A

Levy body dementia
Parkinsons disease

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29
Q

What are the signs/symptoms of Alzheimers disease?

A

Progressive loss of memory, language and reasoning.

30
Q

What is the main reason (NOT cause) of Alzheimers disease pathology?

A

Amyloid plaques and mis-folded tau proteins

31
Q

What drives amyloid production in Alzheimers disease?

A

Infection
Inflammation
Oxidative stress

32
Q

Diagnosis of Alzheimers disease is via brain scan (CT scan + MRI, or CT scan + PET scan). True or false?

A

True

33
Q

What are the resident nerve cells of the brain called?

A

Microglia

34
Q

Which transcription factor supports a shift from M1 (inflammatory) to M2 (anti-inflammatory, neuroprotective) microglia in the brain, positively supporting Alzheimers disease?

A

Nrf2

35
Q

Which chemical/neurotransmitter, produced during enriched social interactions, can act through the vagus nerve to suppress microglia-related inflammation?

A

Oxytocin

36
Q

In what way is oral dysbiosis significantly associated with increased Alzheimers risk?

A

Via P.gingivalis (from periodontitis)

37
Q

Where in the brain does neurogenesis occur?

A

In the hippocampus

38
Q

Which part of the brain is involved in memory storage, mood and cognitive functions?

A

The hippocampus

39
Q

_______ is a neuroprotective protein essential for the survival of cholinergic neurone. Levels of this are significantly decreased in Alzheimers.

A

BDNF (Brain-derived-neurotrophic factor)

40
Q

Healthy gut microbiota support BDNF production so are critical in Alzheimers support. True or false?

A

True

41
Q

Name a neurotrophin

A

BDNF (Brain-derived-neurotrophic factor)

42
Q

Which neurotransmitter do Alzheimers drugs attempt to raise?

A

Acetylcholine (anti-inflammatory neurotransmitter)

43
Q

How can you support acetylcholine in Alzheimers without medication?

A

Acetylcholine is made of mitochondrial Aceytl-CoA and dietary choline. Support these! Healthy diet and lifestyle.

44
Q

Which metal is implicated in Alzheimers disease

A

Aluminium

45
Q

Aluminium concentrations are significantly raised in the brains of patients with Alzheimers Disease. True or false?

A

True

46
Q

How does 20g/day coconut oil support Alzheimers?

A

By boosting ketones for brain energy

47
Q

__________ ___________ is an auto-immune disease that can lead to neurodegeneration.

A

Multiple Sclerosis

48
Q

What is the name of the cells that produce the myelin sheath?

A

Oligodendrocytes

49
Q

What is the myelin sheath?

A

A fat and protein compound that wraps around nerves to support nerve impulses

50
Q

What is the pathophysiology of multiple sclerosis?

A

Autoreactive and inflammatory immune cells infiltrate the blood brain barrier and attack the myelin sheath.

If sustained, this leads to loss of oligodendrocytes and neurodegeneration

51
Q

What is the average of of diagnosis for relapsing-remitting MS?

A

30 years old

52
Q

There are 2 types of MS, list them.

A
  1. Relapsing-remitting (85%)
  2. Primary progressive (15%)
53
Q

Describe primary progressive MS

A

Continuous and progressive loss of neurological function with no remission.
Average age of diagnosis is 45.

54
Q

List 4 signs/symptoms of multiple sclerosis

A

Visual impairment
Nerve tingling / numbness
Intestinal / urinary problems
Fatigue and weakness
Poor coordination and balance
Speech difficulties
Learning and memory issues
Difficulty walking
Emotional difficulties
Muscle spasm/tremors
Pain

55
Q

What is ‘Clinically Isolated Syndrome’? (CIS)

A

When symptoms of MS occur only once.

56
Q

Relapsing-remitting MS often progresses to secondary progressive MS after ___ - ___ years

A

10 - 30 years

57
Q

List 3 proposed risk factors for MS

A

Vitamin D deficiency
Infections (e.g Epstein Barr)
Childhood trauma / stress
Homocysteine
Mitochondrial dysfunction
Cigarette smoke exposure
Certain autoimmune diseases
Environmental toxins
Key vitamin deficiencies - D, K, B12
Obesity

58
Q

MS is considered to be a T-call mediated disease, with a shift in T-cell populations from anti-inflammatory T-rg cells, towards auto reactive Th__ cells.

A

Th17

59
Q

List 2 of the major vitamin deficiencies found in MS patients

A

Vitamin D - deficiency causes more brain lesions and increased relapses.

Vitamin K - Gas6, a vitamin K-dependant anti-inflammatory protein protects oligodendrocytes and promotes remyelination.

Vitamin B12

60
Q

Why is obesity a risk factor for MS?

A
  • It makes the blood-brain barrier more permeable
  • It raises leptin, which is associated with CNS inflammation
  • Leptin increases levels of Th17 autoreactive cells
  • Upregulates M1 microglia, overwhelming protective M2
61
Q

Thymic involution (atrophy) amplifies the production of auto reactive T-cells and predisposes a person to MS. What life event can cause thyme involution?

A

Childhood trauma / abuse

62
Q

The Swank diet is for which pathology?

A

Multiple Sclerosis

63
Q

Which is the second most common neurodegenerative disorder after Alzheimers disease?

A

Parkinsons Disease

64
Q

In which disease is there a gradual loss of dopamine-producing neurons in a part of the brain called the substantia nigra?

A

Parkinsons

65
Q

What leads to the characteristic tremor and movement disorders seen in Parkinsons disease?

A

Loss of dopamine supply to the striatum area of the brain.

66
Q

List 3 signs/symptoms of Parkinsons disease

A

Pill rolling tremor
Muscle rigidity
Shuffling gait
Constipation
Loss of sense of smell
Slow movement, facial expressions and speech

67
Q

List 3 causes / risk factors of Parkinsons Disease

A

Age, heredity, sex
Mitochondrial dysfunction
Oxidative stress
Traumatic brain injury
Pesticides/herbicides
Heavy metal toxicity
Stress / depression
Recreational drugs

68
Q

Essential tremor is a condition that can easily be mistaken for ____________ ___________

A

Parkinsons Disease

69
Q

Which is the signature misfiled protein in Parkinsons disease?

A

Alpha Synuclein

70
Q

What do Alzheimers Disease and Parkinsons have in common?

A

They both have an mis-folded protein associated with their pathology.

71
Q

L-Dopa, the drug used in Parkinsons Disease, is derived from which amino acid?

A

L-tyrosine

72
Q
A