L9 & L10 - Alzheimer's Flashcards
What is neurodegeneration?
Progressive damage or death of neurons leading to deterioration of the bodily functions controlled by the affected part of the nervous system
What is acute vs chronic disorders?
Acute - damage occurs and symptoms present themselves quickly e.g. stroke
Chronic - happens over a long period of time e.g. Alzheimer’s, Parkinson’s
What are the two types of degeneration?
Natural degeneration - Consequence of ageing leading to changes in cognitive function
Disease-induced degeneration - due to illness such as Alzheimer’s
What is dementia?
An umbrella term for a particular group of symptoms
Characteristic symptoms of dementia - memory, language, problem-solving, cognitive ability
Dementia has many causes and Alzheimer’s is a cause of dementia
What is Alzheimer’s disease?
1st identified over 100 years ago
A degenerative brain disorder of unknown origin that causes progressive memory loss, motor deficits and eventual death
Due to higher age population there are more incidences
What is the prevalence of Alzheimer’s disease?
50 million worldwide
1 million people in the UK
1 in 4 people over 65
At the current rate it will be 1.5 million in the UK by 2040
What are the non-modifiable risk factors of Alzheimer’s disease?
Age - most important but age doesn’t equal Alzheimer’s, 65-74yrs = 3%, 75-84yrs = 17%, >85 = 32%
Biological sex - 2x as many women with AD due to them living longer
Genetics
Family history
What are the modifiable risk factors of Alzheimer’s disease?
Cardiovascular disease risk factors - smoking, diabetes, obesity, hypertension, high cholesterol
Relationship between cardiovascular system and brain function
- brain 20% of the blood’s oxygen
- brain function reliant on heart and blood vessel health
- impaired blood flow increases risk
- fatty plaques - cholesterol, salt, age, exercise
What are the recommended preventative factors?
Physical activity
Healthy diet
Social and cognitive engagement
What are the impacts of AD?
Personal
Social
Financial
Societal
e.g. patients, family, carers, NHS, social services, society
Total cost of dementia care = £26 billion per year
What is the continuum of AD symptoms?
Pre-clinical AD - no symptoms
MCI - mild symptoms
Mid - symptoms interfere with some daily activity
Moderate - symptoms interfere with every day life
Severe - can’t look after themself
What are the symptoms of AD?
Early stages - temporary memory lapses, forgetting words/names, difficulty at work, misplacing, difficulty being organised
Middle stages - forgetful of events, confuse words, unable to recall personal info, frustration, sleep disturbances, confusion, bladder problems
Late stages - lose awareness, difficulty in communicating, changes in physical activity
vulnerable to infections
What are the presentation of symptoms dependant on?
Stage of disease
Age
Sex
Other underlying conditions
Patient vs carer reporting
Access to diagnosis
What are the causes of Alzheimer’s?
There is not a single cause for Alzheimer’s
99% is not hereditary
The accumulation of the protein fragment beta-amyloid (plaques) outside neurons
The accumulation of abnormal protein called tau tangles inside neurons are the most prominent
They disrupt normal functioning
What are the two types of Alzheimer’s?
Early-onset - hereditary, <5% of cases, <60-65 yrs
Late onset - majority of cases, >60-65 yrs
What causes early onset AD?
Caused by gene mutations on chromosomes
Chromosome:
1 - presenelin PS1
14 - presenelin PS2
21 - Amyloid precursor protein APP
Autosomal dominant inheritance - if one of these mutated genes is inherited from a parent person will almost always develop early onset AD
What are the causes for late onset AD?
Genetic risk factors involved
e.g. apoliopoprotein E
- glycoprotein, transports cholesterol in blood
- on chromosomee 29 the ApoE gene has 3 alleles
- E4 - one allele of ApoE
- presence of E4 increases risk of AD
B amyloid is soluble except from when ApoE4 is present - making plaques develop
Most causes are sporadic but can be caused by head injuries, alcohol and drugs, toxic exposure, lifestyle factors
What is the brain atrophy of AD?
Severe degeneration of the hippocampus, cerebral cortex and ventricular enlargement
Compared to age matched controls
What are the cellular level features of AD?
Senile plaques (amyloid plaques)
Large quantity and in hippocampus
Amyloid precursor protein
- short, soluble, circulates in blood, activator of kinase enzyme, protects against oxidative stress, regulates cholesterol, anti-microbial actions
In AD patients:
- long, less soluble, accumulate, induce synaptic dysfunction, disrupt neural connectivity, neuronal death, weak correlation
Neurofibrillary tangles (tau tangles)
Non AD - tau stabilises microtubes
AD - tau detaches and disrupts cell’s transport system
What is synaptic loss in AD patients?
Extensive
Depletion of selective neurotransmitter systems
- Acetylcholine
- Glutamate
- Serotonin and Noradrenaline
What is the selective loss of neurotransmitter systems in AD patients?
Neurons that use Ach or glutamate are particularly affected
Neurones that utilise serotonin or noradrenaline are affected
What is the pathology of Alzheimer’s disease?
Cholinergic neurotransmission
1. Acetylcholine production
2. Acetylcholine destruction
These neurons help with learning and memory, certain aspects of sleep states
Antagonists e.g. scopolamine - deleterious effect on learning and memory
Degeneration of Ach producing neurons in forebrain
Deficit in Ach producing enzyme
What are the psychological treatments for AD?
Non-Pharmacological approach
Memory aids - diaries, journals
CBT - reduce depression and anxiety
Music therapy - engage and express feelings
Social interaction - maintain activity
Stimulated presence therapy - using reminders of events from personal events, reduce agitation
What are caregivers as a treatment option for AD?
Attending to another person’s health needs ad well-being
Assisting with activities of daily living
Emotional and practical support
Managing medications/health service interactions
Informal/unpaid
What are the pharmacological treatments for AD?
Cholinergic drugs
Nearly every drug currently licensed for AD = cholinesterase inhibitor
Prolong activity at the synapse
Examples: aricept, donezepil, rivastigmine, galantamine
Glutamate receptor antagonists
Protects brain cells from toxic effects of excessive levels of glutamate
Licensed in the UK for moderate to severe AD
Helps behavioural symptoms
What treatments are in development for AD?
Reducing B amyloid accumulation
- Anti-inflammatory agents
- Enzyme inhibitors
Strategies to reduce tau aggregation
- Anti-inflammatory agents
Improving cardiovascular health
What are biomarkers?
A naturally occurring molecule, gene or characteristic by which a pathological or psychological process can be identified
- found in blood or bodily fluids
- can track healthy functioning, disease diagnosis, monitor response to treatment
AD:
CSF levels of B amyloid and tau
Blood tests of brain derived products
Brain imagining (MRI structural, PET scans)
