Dementia Flashcards
What is meant by the term dementia?
A set of symptoms associated with decline in brain functioning
What is the most common cause of dementia?
Alzheimer disease
What is meant by the term prevalence?
The total number of cases of a condition in the population
What is meant by the term incidence?
The number of newly diagnosed cases of a condition
In the UK, what is the estimated prevalence of dementia?
1.3% or 1 in 79 people
What is the prevalence of dementia in people over the age of 65?
7.1% or 1 in 14
What is the estimated global prevalence of dementia in people 60 and over?
Between 5% - 8%
How many people, globally, are predicted to have dementia by 2050?
131.5 million
How many people, globally, were thought to have dementia in 2015?
46.8 million
What year was Alzheimer’s disease first reported?
1906
What physical changes to the brain were noted when Alzheimer’s was first reported?
- smaller than expected
- cortex covered in localised deposits
- abnormal bundles of fibres (fibrils)
What is meant by the term non-modifiable risk factors?
Those that cannot be altered or changed
What is the strongest risk factor for developing AD?
Age
To what extent does someone over the age of 65’s risk of developing AD increase?
Roughly doubles every five years
Roughly how many people over the age of 80 are affected by AD?
1 in 6
Is there a difference in prevalence of AD between genders?
Yes - higher in women than in men
What is an allele?
Any of several variants of the same theme formed through mutation
Approximately what percentage of cases of AD develop due to genetic mutations?
1-5% of cases
What are the names of the three proteins which, if mutated, can cause AD?
- Amyloid precursor protein (APP)
- Presenilin 1 (PS1)
- Presenilin 2 (PS2)
What is beta amyloid peptide?
A peptide which is the main component of the amyloid plaques seen in the brains of people with AD
What does autosomal dominant mean?
That only one copy of the mutation needs to be inherited for the condition to occur
Dementia onset lower than what age is considered to be early-onset?
65
What is meant by the term sporadic AD?
The type of AD where the cause is not known
What is the name of the allele which is found in approximately 50% of people with AD?
APOE4
What does the protein produced by the APOE4 gene do?
It is involved in the transport of cholesterol and other lipids around the body
Of the three major alleles of the APOE gene, which is themost common in the general population?
APOE3
Of the three major alleles of the APOE gene, which seems to provide a ‘protective’ effect against AD?
APOE2
What are epigentic mechanisms?
Those which control the silencing and activation of genes
Acetylation involves the addition of acetyl groups to what?
Histones
In general, increased methylation does what?
Reduces gene transcription
In general increased acetylation does what?
Increases gene transcription
What effect would a decrease in DNA methylation have on gene transcription?
It would result in an increase in gene transcription - genes that would normally be silenced become more active
Broadly speaking, what are the three main modifiable risk factors for AD?
- Metabolic and vascular factors
- Diet and nutrition
- Lifestyle
What are two examples of metabolic and vascular factors which increase the risk of AD?
- Diabetes
- Hypertension (high blood pressure)
What are the four non-modifiable risk factors for AD?
- Age
- Biological sex
- Genetic factors
- Race and ethnicity
What dietary factors can increase the risk of developing AD?
- High levels of saturated fats
- Low folic acid
- Low vitamins B6 and B12
What is the connection of folic acid to the potential of developing AD?
It plays an important role in the catabolism of the amino acids methionine and homocysteine
What social factors can increase the risk of developing AD?
- Increased isolation
- Low socioeconomic status
- Low level of education
- Non-engaging job
Women and ethnic minorities are at a higher or lower risk of developing AD than men and Caucasian populations?
Higher
How might hearing loss be a risk factor for developing AD?
- It may result in atrophy of some brain areas
- Struggling to hear could prevent other cognitive functions from taking place
- Loss of hearing could result in social isolation and withdrawal from mentally stimulating activities
Will all people with mild NCD (neurocognitive disorders) progress to major NCD?
No, the conversation rate is approximately 10% per year
What does validity mean in reference to scientific tests?
Whether a test is well-designed and measures what it is intended to measure
What does reliability mean with regards to scientific tests?
The extent to which an evalution is accurate and yields the same results when used by different clinicians or researchers
Does a diagnosis of major NCD mean that an individual has AD?
No, it is made if the person has major NCD and there is additional evidence for AD
At what point is it possible to definitively diagnose AD?
Post-mortem
What are the physical characteristics of AD within the brain?
- Brain atrophy
- Accumulation of neurofibrillary tangles inside neurons
- Deposition of amyloid plaques outside cells
In general, AD is characterised by overall atrophy and thinning of the cortex in which areas of the brain?
- Parietal
- Frontal and temporal lobes
- Corpus callosum
What happens to the size of the ventricles in patients with AD?
They shrink
What is the corpus callosum?
A large bundle of neurons that connects the two hemispheres of the brain, allowing them to communicate with each other
Which two regions of the brain are involved in memory?
- Hippocampus
- Temporal lobe
Which region of the brain is involved with speech and language?
Temporal lobe
Which region of the brain is associated with reasoning and problem solving?
Frontal lobe
AD causes disorientation and motor impairment due to affecting which regions of the brain?
- Hippocampus
- Parietal lobe
- Frontal lobe
Where in the brain is the hippocampus located, in relation to the cortex?
The hippocampus is a medial part of the temporal lobe, so it is located towards the centre of the brain relative to the cortex
What is the role of CSF?
- Cushioning and buoyancy of the brain
- Physical protection of the brain
- Regulation of brain pressure
- Clearance of waste products from the brain
In which mental health condition is reduced ventricle size also observed?
Schizophrenia
Death of what in the brain is the cause of atrophy due to AD?
Neuronal cell bodies and fibres
What actually are neurofibrillary tangles?
Defects in the microtubules within a neuron
Which type of neurotransmitter pathway dies early on in AD?
Acetylcholine
Dopaminergic neurons are lost at which stage of AD?
Later stages
Neuronal loss in the cholinergic pathways would cause which symptoms seen in AD?
- Memory loss, including spatial memory
- Cognitive impairments
What is thought to be a key contributor to why neurons die due to AD?
Amyloid plaques
From what parent protein is the amyloid peptide cleaved?
Amyloid precurser protein
In the non-amyloidogenic pathway, APP is cut by which enzymes?
Alpha-secretase near the membrane, gamma-secretase in the remaining portion
Where does the enzyme beta-secretase cut APP?
Outside the neuronal membrane
How many amino acids are in the form of beta-amyloid that is most increased in AD?
42
What are the mechanisms of removal of amyloid beta from the brain?
- Proteolytic breakdown
- Phagocytosis
- Removal into lymphatic system
- Clearance across blood-brain barrier
What causes atherosclerosis?
The build-up for fat, cholesterol and other substances
What cardiovascular risk factors increase the risk of developing AD?
- Hypercholestoremia
- Hypertension
- Smoking
- Diabetes
What is the name for the accumulation of amyloid beta in the walls of the blood vessels of the brain?
Cerebral amyloid angiopathy
What damage to blood vessels does aggregated amyloid beta cause?
- Damage to endothelial cells
- Death of smooth muscle cells in the blood vessel walls
- Loss of tight junction proteins between cells
- Structural changes to the astrocytes that exist around blood vessels
What are microtubules?
Structures that provide support to cells and also move molecules and cell components from one part of the cell to another
How are microtubules formed?
By the assembly of a protein called tubulin into protofilaments that associate to form hollow tubes
What is Tau?
A protein associated with microtubules that is the main component of the neurofibrillary tangles seen in the brains of people with AD
What is phosphorylatio?
The process by which a phosphate group is added to an amino acid
Which enzyme mediates addition of phosphate to amino acids?
Kinase
Which enzyme mediates removal of phosphate from amino acids?
Phosphatase
What qualities can phosphorylation of a protein change?
Its solubility, localisation within the cell, function and interaction with other proteins
Under normal conditions, what does phosphorylation of tau in the microtubule-binding region contribute to?
- Regulation of neuronal growth
- Axonal transport
- Stabilisation of microtubules
