Alzheimer's

Question 1

What is known as progressive damage or death of neurons leading to a gradual deterioration of the bodily functions controlled by the affected part of the nervous system?

Answer 1

Neurodegeneration

Question 2

Which disease is a degenerative brain disorder of unknown origin that causes progressive memory loss, motor deficits, and eventual death?

Answer 2

Alzheimer’s Disease

Question 3

What are the Non-modifiable factors of Alzheimer’s?

Answer 3

But mostly a combination of genetics and environmental factors

Question 4

What are the Modifiable factors of Alzheimer’s?

Answer 4

But mostly a combination of genetics and environmental factors

Question 5

What happens at the early stages of Azheimer’s?

Answer 5

Changes in brain function aren’t sufficient to = symptoms
Compensatory mechanisms may activated

Some changes in brain function (e.g. beta-amyloid levels)
may occur up to 20 years before symptoms

Question 6

What are the early signs of Alzheimer’s?

What do these usually progress to?

Answer 6

When aging:
‘Blunting of emotional responses’
Social withdrawal

Progress to
Episodic Memory Impairment
Progressive memory loss (initially episodic and declarative)

Impairment in function
Memory, insight, judgement, language

Changes in personality
Apathy, indifference, depression

Question 7

Name the symptoms of Alzheimer’s:
At early
Middle
Late stages

Answer 7

Question 8

Name a specific advanced stage of Azheimer’s:

Answer 8

Gross disorientation in time and place
Little awareness of past or future

Total dependence on carer for ‘everyday’ tasks

Inability to comprehend/communicate

Little mobility – difficulty in swallowing – infections
(e.g. sepsis, pneumonia)

Question 9

What causes brain dysfunction associated with Alzheimer’s?

Answer 9

The accumulation of the protein fragment
beta‐amyloid (called beta‐amyloid plaques)outsideneurons

and the accumulation of an abnormal form of the protein tau (called tau tangles)insideneurons are the most prominent brain changes associated with Alzheimer’s.

Question 10

Name the 2 main types of Azheimer’s:

Answer 10

Early-onset
Hereditary
<5% cases
<60 -65 yrs under age of 65 (rarer type)

Late-onset
Majority cases
> recieving diagnosis over 60-65 yrs

Question 11

Early-onset of Alzheimer’s which is hereditary and diagnosed under the age of 65 is cause by?

Answer 11

Early onset AD
Caused by gene mutations on chromosomes

Question 12

What does it mean when the early onset of Alzheimer’s has Autosomal dominant inheritance?

Answer 12

If one of these mutated genes is inherited from a parent – person will almost always develop early onset AD
(Rarest form of A)

Question 13

The late onset Alzheimer’s still has some genetic risk factors involved such as Apolipoprotein E (apoE).
Explain it’s relevance:

Answer 13

Apolipoprotein E (apoE):

gylcoprotein, transports cholesterol in blood,
which plays a role in cellular repair

On chromosome 19, ApoE gene has three common forms or alleles: E2, E3, and E4.

Thus, the possible combinations in one person* are
E2/2, E2/3, E2/4, E3/3, E3/4, or E4/4
(*we inherit one form from each parent).

E4 = one allele of ApoE
Presence of E4 = increases risk of developing AD (does not cause AD)

Question 14

Which allele of ApoE increases risk of developing AD (does not cause AD)?

Answer 14

E4

Question 15

What are Alleles?

Answer 15

Different forms of the same gene.

Two or more alleles can shape each human trait.
Each person receives two alleles, one from each parent.

This combination is one factor among many that influences a variety of processes in the body.

Question 15

Late onset AD
Most cases of AD are sporadic. What does this mean?

Answer 15

(i.e. not hereditary)

Question 16

What causes b-amyloid accumulation?

Answer 16

Head injury, infections, excessive alcohol or other drugs, exposure to toxic substances, lifestyle factors

Question 17

Brain atrophy

Answer 17

Brains between groups of patients with/without Alzheimer’s
should be age-matched due to the natural aging process of brain changing.

Question 18

Brain atrophy:
What will patients with Alzheimer’s brain look like on an MRI scan?

Answer 18

Severe degeneration of the
hippocampus, cerebral cortex and ventricular enlargement

Question 19

What will patients with Alzheimer’s brain look like at a cellular level?

Answer 19

Formation of Senile/ Amyloid plaques
Occur outside of the neuronal body but interfere with neuronal functions and processing

Neuron dies

However, plaques are not unique to AD, as we age plaques develop in nervous system
But are high in quantity and specific of plaques is found within the hippocampus in people with AD

Question 20

Cellular Level Features:
What are the normal functions of b-amyloid (Ab)

Answer 20

mostly short form, soluble, circulate in CSF/blood
activator of kinase enzymes
protects against oxidative stress
regulation of cholesterol transport
anti-microbial actions

Question 20

Cellular Level Features:
What are the ABnormal functions of b-amyloid (Ab) for patients with Alzheimer’s disease?

Answer 20

increased portion of long form
long form – less soluble, more likely to accumulate
induce synaptic dysfunction, disrupt neuronal connectivity and result in neuronal death
weak correlation in quantity and distribution + AD

Question 21

Synaptic loss:
Name the selective neurotransmitter systems that could be depleted by Alzheimer’s .

Answer 21

Depletion of selective neurotransmitter systems:
Acetylcholine (Ach)
Glutamate
Serotonin
Noradrenaline

Question 22

Name Psychological (non-pharmacological) approaches to treating Alzheimer’s

Answer 22

Memory Aids
diaries, journals, lists,

Cognitive Behavioural Therapy (CBT)
aimed at reducing depression/anxiety (rather than specifically AD)

Music Therapy
to help engage and express feelings

Structured social interaction
Allows a carer to maintain an activity/contact with a patient for 10-15 mins/day -later stages

Stimulated presence therapy
Using reminders of events from their personal life
Helps reduce agitation and restlessness

Question 23

Care giving of Alzheimer’s:

Answer 23

Attending to another person’s health needs and well-being
Assisting with activities of daily living
Emotional and practical support
Managing medications/health service interactions
Informal/unpaid (family members)
The burden of stress of the caregiver!

Question 24

Which types of drugs are prescribed to those with Alzheimer’s?

Answer 24

Cholinergic drugs

Eg. Aricept, donezepil, rivastigmine, galantamine
Nearly every drug currently licensed for AD = cholinesterase inhibitor (ChEI)

Question 25

What do Cholinergic drugs do?

Answer 25

Boosts activity at cholinergic synapses

Aricept, donezepil, rivastigmine, galantamine
Licensed (in UK) for mild to moderate AD, transiently improves clinical symptoms for 6-12 months

Question 26

Name the Glutamate receptor antagonist which is prescribed for patients with AD:

Answer 26

Memantine (NMDA receptor antagonist)

Protects brain cells by blocking the toxic effects of excessively high levels of glutamate

Licensed (in UK) for treatment of moderate-to-severe AD
(later stages)
Shown to temporarily slow the progression of symptoms
Helps behavioural symptoms such as aggression and agitation

Question 27

What are the treatment approaches in development?

Answer 27

Strategies to reduce b-amyloid accumulation
- Anti-inflammatory agents
(info in the CNS is more inducive to the amyloid plaques, so if we reduce that inflammation then we may decrease the build-up)
- Enzyme inhibitors that decrease the production of b-amyloid (specifically the longer form which is less soluble= build up)

Strategies to reduce tau aggregation and accumulation via
- Anti-inflammatory agents

Improving cardiovascular health
- Health of blood vessels in brain

Question 28

What are naturally occurring molecules, genes, or characteristics by which a particular pathological or physiological process, disease can be identified?

Answer 28

Biomarkers

Question 29

Where are Biomarkers found?

Answer 29

Found in blood, other body fluids, organs and tissues

Question 30

What is the function of Biomarkers?

Answer 30

Can track healthy functioning,
diagnose disease,
monitor response to treatment,
identify health risks
(e.g. high cholesterol/high blood pressure for cardiac disease)

Question 31

How are Biomarkers Specific to Alzheimer’s Disease?

Answer 31

We can diagnose AD many years before symptoms surface

Give them treatments preventing symptoms from ever occurring

Do this by doing
Brain imaging studies:
MRI/CT – structural changes in brain (*need age comparison)
Amyloid or Tau PET scans – to examine the accumulation of amyloid/tau
Fluorodeoxyglucose PET scans – to examine energy i.e. glucose, use in brain

To look at:
CSF levels/changes of B-amyloid and/or tau
Blood tests of brain-derived products