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.