L9 & L10 - Alzheimer's

Question 1

What is neurodegeneration?

Answer 1

Progressive damage or death of neurons leading to deterioration of the bodily functions controlled by the affected part of the nervous system

Question 2

What is acute vs chronic disorders?

Answer 2

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

Question 3

What are the two types of degeneration?

Answer 3

Natural degeneration - Consequence of ageing leading to changes in cognitive function
Disease-induced degeneration - due to illness such as Alzheimer’s

Question 4

What is dementia?

Answer 4

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

Question 5

What is Alzheimer’s disease?

Answer 5

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

Question 6

What is the prevalence of Alzheimer’s disease?

Answer 6

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

Question 7

What are the non-modifiable risk factors of Alzheimer’s disease?

Answer 7

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

Question 8

What are the modifiable risk factors of Alzheimer’s disease?

Answer 8

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

Question 9

What are the recommended preventative factors?

Answer 9

Physical activity
Healthy diet
Social and cognitive engagement

Question 10

What are the impacts of AD?

Answer 10

Personal
Social
Financial
Societal
e.g. patients, family, carers, NHS, social services, society
Total cost of dementia care = £26 billion per year

Question 11

What is the continuum of AD symptoms?

Answer 11

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

Question 12

What are the symptoms of AD?

Answer 12

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

Question 13

What are the presentation of symptoms dependant on?

Answer 13

Stage of disease
Age
Sex
Other underlying conditions
Patient vs carer reporting
Access to diagnosis

Question 14

What are the causes of Alzheimer’s?

Answer 14

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

Question 15

What are the two types of Alzheimer’s?

Answer 15

Early-onset - hereditary, <5% of cases, <60-65 yrs
Late onset - majority of cases, >60-65 yrs

Question 16

What causes early onset AD?

Answer 16

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

Question 17

What are the causes for late onset AD?

Answer 17

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

Question 18

What is the brain atrophy of AD?

Answer 18

Severe degeneration of the hippocampus, cerebral cortex and ventricular enlargement
Compared to age matched controls

Question 19

What are the cellular level features of AD?

Answer 19

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

Question 20

What is synaptic loss in AD patients?

Answer 20

Extensive
Depletion of selective neurotransmitter systems
- Acetylcholine
- Glutamate
- Serotonin and Noradrenaline

Question 21

What is the selective loss of neurotransmitter systems in AD patients?

Answer 21

Neurons that use Ach or glutamate are particularly affected
Neurones that utilise serotonin or noradrenaline are affected

Question 22

What is the pathology of Alzheimer’s disease?

Answer 22

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

Question 23

What are the psychological treatments for AD?

Answer 23

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

Question 24

What are caregivers as a treatment option for AD?

Answer 24

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

Question 25

What are the pharmacological treatments for AD?

Answer 25

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

Question 26

What treatments are in development for AD?

Answer 26

Reducing B amyloid accumulation
- Anti-inflammatory agents
- Enzyme inhibitors
Strategies to reduce tau aggregation
- Anti-inflammatory agents
Improving cardiovascular health

Question 27

What are biomarkers?

Answer 27

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)