Brain Health and Dementia 1b Flashcards
What happens to the body with time?
The body deteriorates with time
The rate of cell division slows
Structural changes due to damage
and inappropriate metabolism accumulate
Organ function decreases
Why does the body deteriorate over time?
Rate of cell division slows as a result of shrinking telomeres, which shrink each time the cell divides.
Why do telomeres shrink?
shrinking of telomeres may be natures way of timing and programming our death.
What percentage of people over the age of 60 have dementia?
7.1%
How does a persons risk of dementia change from over the age of 60 to over the age of 80?
A persons risk of developing dementia rises from one in 14 over the age of 65 to one in six over the age of 80.
How many people under the age of 65 have dementia?
over 42,000. Thats 5.2%
What age group is most likely to get dementia?
80-84 in both genders. RIsk increases with age.
In what gender is dementia most prevalent?
Females.
What age groups in men and women are living with the most dementia?
80-84 in men. 85-89 in women
What is the function of apolipoprotein (ApoE)?
Transport of cholesterol to neural cells
What are the different types of lipoprotein?
Apolipoprotein E ε2 / ε3 / ε4
What are certain isoforms of ApoE thought to do?
Certain isoforms of ApoE are thought to affect synaptic survival and efficiency.
What happens in the brain of people with the ApoE ε4 allele?
- higher oxidative stress
- increased β-amyloid accumulation
What forms of dementia is ApoE ε4 influential in?
The APOE ε4 allele is influential in Alzheimer’s disease but might also be of importance in
vascular dementia and in mixed dementia diseases
Describe the article “Apolipoprotein E, Cognitive Function, and Dementia in a General Population Aged 85 Years and Over”
The results of our study do not support the hypothesis that the Apo-E ε4 allele is associated with impaired cognitive
functions of non-demented very old people […] This study does not support the hypothesis that the Apo-E ε4 allele
impairs cognitive functions of non-demented elderly, at least in those surviving to very old age […] There was a
significant sex difference: the Odds ratio in women was 3.23 (95% CI 2.02 - 5.17) it was insignificant amongst men
What does low plasma levels of ApoE increase the risk of?
Low plasma levels of ApoE are associated with increased risk of future Alzheimer’s disease and
all dementia in the general population, independent of ε2/ε3/ε4 APOE genotype. This is clinically relevant, because no plasma biomarkers are currently implemented.
What is the relationship between conditions that are known to increase risk of CVD and dementia?
Conditions that are known to heighten the risk of CVD are associated with an increased risk of dementia
Why do conditions that heighten the risk of CVD increase risk of dementia?
alterations in blood flow in the brain resulting in areas of brain injury, thus increasing likelihood of dementia.
What CVD related conditions increase risk of dementia?
Angina
High capillary pressure
Oedema
Microvascular disease (coronary, cerebral)
Microvasculature arteriosclerosis (thickening, hardening and loss of elasticity)
Stroke (ischemic and/or hemorrhagic)
What affect can high blood pressure have on the brain?
High blood pressure can have dramatic consequences.
What damage can chronic hypertension (high blood pressure) cause to the brain?
- damage to the vascular endothelium
- altered neurovascular unit.
- can affect structure of both white and grey matter
What parts of the brain are most commonly affected by hypertension?
- pre-frontal cortex
- hippocampus
How is untreated high blood pressure and genetics linked to Alzheimers?
A research team found that the combination of genetic predispositon and non-medicated high blood pressure can lead to a protein buildup that some scientists believe is linked to Alzheimers.
What is hypercholesterolaemia
High blood cholesterol
What are the functions of cholesterol for neurological health?
Cholesterol has important functions in neurological health
- synaptogenesis (formation of synapses)
- regulation of the turnover of β-amyloid plaques
Describe cholesterol and it being a risk factor of AD.
- “These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia.”
- Positive association between high homocysteine and high cholesterol levels - factor in the development of dementia.
What can stress and depression increase the release of?
Stress and depression can cause increased release of glucocorticoids (cortisol)
How do glucocorticoids negatively affect memory?
Hippocampal neurons can be damaged by long-term high exposure to glucocorticoids,
negatively affecting memory
What does recent research suggest stress and depression are early signs of?
Recent research suggests chronic stress and depression could merely be early symptoms of
dementia.
Describe how anxiety can increase risk of dementia.
- “Pathological anxiety and chronic stress lead to structural degeneration and impaired functioning of the hippocampus and the prefrontal cortex, which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia. -
- Longitudinal studies are needed to
determine whether reversal of stress-induced brain changes by interventions such as cognitive-behavioural therapy can reduce
risk of neuropsychiatric illness.”
How does insulin resistance increase risk of AD / dementia?
- increased Advanced Glycation End Products (AGEs)
- Increased accumulation of β-amyloid plaques
- AGEs impair myelin structure
How does diabetic neuropathy occur?
1) Chronic hyperglycaemia
2) Increase in AGEs Products
3) Increased Oxidative Stress
4) Microvascular Damage
5) Diabetic Neuropathy
What do oligodendrocytes do?
produce myelin
How does dementia affect the sleep of older adults?
Older adults with dementia exhibit significant sleep disturbance, including:
- shorter sleep duration
- fragmented sleep
- altered circadian rest/activity patterns
- elevated rates of sleep-disordered breathing (SDB)
- Obstructive Sleep Apnoea (OSA
- Central Sleep Apnoea (CSA)
- Mixed or complex sleep apnoea
What is SDB?
sleep-disordered breathing (rates elevated in dementia.)
What is Obstructive Sleep Apnoea (OSA)?
partial or full upper airway collapse during sleep
What is Central Sleep Apnoea (CSA)?
CNS disorder where the breathing centre in the brain fails to trigger breathing or the signal to inhale is not transmitted properly to the rest of the body. Brain fails to trigger respiratory muscles.
What is Mixed or complex sleep apnoea?
Combination of OSA and CSA.
Is sleep disturbance a risk factor of AD?
Yes
Why is an association between poor sleep and AD critical?
could be of critical importance to AD prevention
because effective interventions exist to improve sleep
What does poor sleep include?
Poor sleep includes
insomnia symptoms:
–difficulty falling asleep
–difficulty staying asleep
–poor sleep quality
- Short and long sleep duration
- Sleep-disordered breathing (SDB)
How does obesity increase risk of dementia?
Obesity = mild chronic inflammation
Increased oxidative stress
Insulin resistance –> glycation
Increased levels of pro-inflammatory cytokines
Temporal lobe atrophy
Reduction in hippocampal volume
Describe the relationship between obesity/overweightness and cognitive decline.
In addition to increasing the risks of developing
dementia and AD, being overweight or obese is
associated with cognitive decline, brain atrophy, white matter changes, and disturbances of blood-brain barrier integrity.
What is estradiol?
a hormone
What is the function of estradiol?
Estradiol has neuroprotective actions
in brain regions such as the hippocampus:
- reduces oxidative damage
- limits the damage caused by β-amyloid plaque accumulation
Describe the relationship between estradiol levels and odd of decline.
the higher estradiol levels (red arrow)
the lower odd of decline (orange arrow)
Therefore, low levels of estradiol = higher odds of decline
What medications are used to improve the central nervous system?
High doses and concurrent use of medications:
- Antidepressants:
fluoxetine, amitriptyline, sertraline, etc…
- Antipsychotic:
chlorpromazine, haloperidol, risperidone, etc…
- Benzodiazepines: (sedatives and tranquilizers)
diazepam, lorazepam, clonazepam, etc…
- Opioid analgesics:
methadone, morphine, tramadol, codeine, etc…
What are Benzodiazepines used for?
Used for insomnia and anxiety. Slows the brain down.
What cytokines are produced during an infection?
Pro-inflammatory cytokines such as:
IL-1 (interleukin-1)
IL-6
IL-8
TNF alpha (Tumour necrosis factor)
IFNy (interferon gamma)
What is IFNy used to treat?
IFNy (interferon gamma) is used to treat arthritis and other diseases which are inflammatory.
Some areas of the hippocampus are more susceptible to…
tissue damage. Such as the part of it which is responsible for long term memory.
What makes a persons hippocampus more susceptible to tissue damage?
Advancing age makes an individual much more susceptible to this effect
Why does chronic inflammation cause more damage?
more damaging - inflammation for a longer period of time.
How does traumatic head injury increase risk of dementia?
Following traumatic head injury, increased β-amyloid accumulation is seen, resulting in neurodegeneration, leading to neurons dying.
When is head trauma NOT a risk factor?
mild head trauma is not a major risk factor for dementia or AD in the elderly.
If head trauma is mild, it is not necessarily a risk factor.
What conclusion from research studies and post mortem studies support the link between traumatic head injuries and dementia?
“Both human post-mortem and experimental studies showing apolipoprotein beta deposition and tau pathology after head injury support the link between traumatic brain injury and dementia, and further studies are warranted to clarify this relationship.”
What does excessive alcohol intake lead to?
Excessive alcohol intake can lead to:
- increased levels of homocysteine
- reductions in the amount of grey matter
- increasing ventricle volume (ventriculomegaly)
What is Hyperhomocysteinemia associated with?
a. Endothelial Cell Injury
b. Atherogenesis
c. Ischemic Injury
Describe wine vs risk of dementia.
wine had a protective effect against dementia
Describe spirits vs risk of dementia.
consumption of spirits at baseline was associated with slightly increased risk of dementia
Describe associations of wine and spirits with dementia.
Results show that wine and spirits displayed opposing associations with dementia.
Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.
Smoking is also a…
risk factor of dementia.
Describe how smoking increases risk of dementia.
One puff of the gas-phase contains 10^15 organic radical molecules .
the tar around 10^14 organic radical molecules:
alkyl, alkoxyl, peroxyl, etc…
These can react with and alter the structures of
- DNA
- RNA
- protein
- unsaturated fatty acids
—lipid peroxidation
—fatty acids in membranes cross link
—same process as oil paint cures (goes hard)
—contributory element in Alzheimer’s disease
How does smoking double risk of dementia?
- Increasing the risk of cardiovascular disease, diabetes, stroke.
- Narrowing the blood vessels in the heart and brain
- Causing oxidative stress which damages the brain.
How can dementia be prevented?
1) Reduced neuropathological damage (amyloid or tau-mediated, vascular or inflammatory).
2) Increased and maintained cognitive reserve.
How to achieve Reduced neuropathological damage?
- Minimise diabetes
- Treat hypertension
- Prevent head injury
- Stop smoking
- Reduce air pollution
- Reduce midlife obesity
- Maintain frequent exercise
- Reduce occurrence of depression
- Attain high level of education
- Maintain frequent exercise
- Reduce occurrence of depression
- Attain high level of education
- Treat hearing impairment
- Maintain frequent social contact
- Attain high level of education
What does long term physical activity increase the release of?
- Brain-derived neurotrophic factor (BDNF)
- dopamine
- serotonin
What does physical activity affect?
Effects on:
neurogenesis
neuronal survival
plasticity of the brain tissue
efficient functioning of synapses
synaptogenesis
Define plasticity (of the brain).
Malleable. can change. plasticity can change, for better or for worse. One big mechanism in plasticity is the ability to learn new things.
What do evidence from clinical trials suggest about BDNF?
Evidence from clinical trials suggests that treatment strategies aiming to increase brain
BDNF levels could have a beneficial effect on many brain disorders.
How does physical activity alleviate symptoms of brain pathologies?
Environmental and physiological stimuli, such as physical activity, social interactions, and
sensory and cognitive stimuli, are powerful modifiers of neurotrophin levels, including BDNF levels, and have been shown to alleviate symptoms of brain pathologies.
Describe relationship between level of education and Brain Reserve Capacity (BRC).
higher levels of education have a positive association with greater Brain Reserve Capacity (BRC).
What is Brain Reserve Capacity (BRC)?
brain’s resilience to pathological damage or changes. The greater the brain reserve capacity, the less likely an individual will demonstrate behavioural disturbance associated with a disease.
Also possible protection against β-amyloid deposition.
How does education help to lower the risk of AD?
Education may increase regional cortical thickness in healthy controls, leading to increased brain reserve, as well as helping AD patients to cope better with the effects of brain atrophy by increasing cognitive reserve.
Describe the cortical thickness of healthy controls who had more education?
The healthy controls with more education had greater cortical thickness than those with less education at the transverse temporal cortex, isthmus cingulate, and insula.
Describe the transverse temporal cortex, isthmus cingulate, and insula of healthy controls with more education.
- increased thickness of transverse temporal cortex in those in higher education.
- Increased thickness of isthmus cingulate in those who have had more education.
- Increased thickness of insula in those who have had more education.
The longer-term impacts of Western diet on human cognition and the brain
mandatory reading !
Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer’s Disease and Late-Life Cognitive Disorders: A Systematic Review
mandatory reading !
Describe the energy requirement of the brain?
Brain tissue consumes a large amount of glucose in proportion to its volume
~ 120 g daily –> ~ 60% of total glucose utilisation.
The brain which is an organ which represents 2% of our mass uses up 60% of our total glucose.
Compare typical human body weight to human brain weight.
Typical human body weight ~ 70,000 g (70 Kg)
human brain weight ~ 1,300-1,500 g (approx. 2%)
What percentage of basal metabolism occurs in the brain?
Humans ~ 20-25% basal metabolism in the brain.
What do neurons do?
Neurons transmit signals/information using these charges.
How is membrane potential of neurons sustained bitch?
Sustain the membrane potential of neurons:
via Na+/K+-ATPase pump.
O2-dependent glucose metabolism
What are some clinicians calling AD?
“type III DM” (type 3 diabetes mellitus).
Describe the brain and its ability importing glucose.
The brain seems to have a reduced ability to import glucose just like muscles do in Impaired
Glucose tolerance
Why does the brain have a reduced ability to import glucose?
this is likely to be due to over indulgence in high carbohydrate foods containing large amounts of free sugars (sugars that dissolve quickly in gastric acid and so can rapidly enter the blood stream).
What does the brains reduced ability to import glucose result in?
The result is a lack of energy and thus perhaps the inability to process and degrade waste proteins
–> Alzheimer’s disease and Lewy body dementia?
Hyperglycaemia can lead to hypertension and vascular damage
–> vascular dementia
What fuels other than glucose can the brain use?
Ketones, medium chain fatty acids (eg coconut oil), amino acids.
These can have consequences.
Describe ketones and its affect on the brain
can enter the brain by a different transporter than glucose
can feed in to the Krebs cycle
some people including those with dementia do appear to have increased brain functionality
ketones can have detrimental affects on health (adequate management
Describe medium chain fatty acids (eg coconut oil) and its effect on the brain.
directly enters the brain and can feed in to the Krebs cycle
the liver destroys them on site which implies they are regarded as toxic
likely due to the fact they can enter membranes and disturb their structure
What is a major cause of brain dysfunction?
Lack of oxygen to neurons.
What is needed to meet the energy requirements of the brain?
you need the Krebs cycle to be functional in order to meet the energy requirements of the brain.
What nutrients involved in promoting correct oxygenation of the blood are an issue?
- iron (iron deficiency anaemia)
- folate ; B9 (megaloblastic anaemia)
- cobalamin ; B12 (pernicious anaemia)
What is essential for energy production?
Many vitamins and minerals are essential for energy production
What vitamins are required for successful oxidation of glucose?
B1, B2, B3, B5 are all required for successful oxidation of glucose via glycolysis and the Krebs cycle
What minerals are needed to make the proteins involved in oxidative phosphorylation?
Iron, copper and sulfur are needed to make the proteins involved in oxidative phosphorylation.
What happens as a result of impaired energy production?
Impaired energy production results in greater production of oxidants
these can cause damage
need antioxidants to reduce damage – eat your colour veg
most powerful antioxidant in brain is called melatonin
When and how is melatonin made?
made when the organism sleeps (sleep duration, sleep quality)
made from serotonin, which needs blue light (sun exposure)
made from the amino acid trypotaphan (protein intake)
What is the most powerful antioxidant in the brain?
melatonin
What do antioxidants do in the brain?
reduce damage caused by (excess) oxidants.
What percentage of the brain is lipid excluding water?
Excluding water the brain is
composed of ≈ 56-60% lipids
Where are lipids in the brain?
in the membranes of cells (neurons and others)
Why is cholesterol necessary?
We do not want too much cholesterol in our diet however some cholesterol is necessary to maintain the fluidity of our cell membrane. With no cholesterol, our membranes would be too rigid.
What fatty acids and polyunsaturated fatty acids were found in AD patients in post mortem examinations?
Main results:
blood (in vivo) and brain (post-mortem) of patients with AD
- high SFA
- high omega-6 PUFA
- low omega-3 PUFA
WHat are the effects od supplementing patients with MCI with ω-3 and antioxidants?
“In conclusion, this pilot study shows that the supplementation of patients with mild cognitive
impairment by ω-3 and antioxidants improves anti-Aβ immunity […]. In addition, the result suggests cognitive stabilization in comparison to historical controls.”
What are the 3 largest sources of vegetable oil in the world?
- rapeseed
- sunflower
- soybean
What are vegetable oils major sources of?
omega 6 (linoleic acid)
Out of rapeseed, sunflower, and soybean oil, which contains the lowest amount of omega 6?
Rapeseed has the lowest amount of omega 6 (20-40%).
Out of rapeseed, sunflower, and soybean oil, which contains the highest amount of omega 6?
sunflower oil (50-60%)
Out of rapeseed, sunflower, and soybean oil, which contains the medium amount of omega 6?
Soybean oil (45-75%).
How much EPA does Tuna contain?
Tuna (fresh tuna, not canned tuna) contains a high amount of EPA. Macrel also contains alot of EPA. Salmon does not contain as much EPA.
WHat is EPA?
EPA is an essential fat/nutrient which the body needs.
WHats a PUFA?
polyunsaturated fatty acids
PUFAS are…
an essential fatty acid.
Can PUFAs be synthesised de novo?
No. They have to be ingested.
What is arachidonic acid and where is it found?
Arachidonic acid (AA) is found in red meats. Contains lots of omega 6.
What does recent animal work suggest about western diets?
Animal work over the last three decades has generated a convincing body of evidence that a Western diet - one high in saturated fat and refined carbohydrates (HFS diet) - can damage various brain systems
Why is a western diet unhealthy?
They are high in saturated fat and refined carbohydrates (HFS diet).
What is a HFS diet?
Stands for high-fat sucrose diet. Its a diet which is high in fat, and high in sugar. Sometimes fed to animals to simulate the diet that a typical American consumes.
In “The longer-term impacts of Western diet on human cognition and the brain”, what was used to examine whether there is evidence for the hypothesis that HFS diets can cause brain impairment in humans?
using converging lines of evidence from neuropsychological, epidemiological and neuroimaging data.
In “The longer-term impacts of Western diet on human cognition and the brain” what parts of the brain were examined?
Using the animal research as the organizing principal, we examined evidence for dietary induced impairments in frontal, limbic and hippocampal systems, and with their associated functions in learning, memory, cognition and hedonics.
Evidence for the role of HFS diet in attention deficit disorder and in neurodegenerative conditions was also examined.
Is there evidence of an association between HFS diet and impaired cognitive function?
While human research data is still at an early stage, there is evidence of an association between HFS diet and impaired cognitive function.
In “The longer-term impacts of Western diet on human cognition and the brain” what was the causal link they saw?
there is a causal link running from HFS diet to impaired brain function in humans, and that HFS diets also contribute to the development of neurodegenerative conditions.
