Alzheimer's Flashcards
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?
Neurodegeneration
Which disease is a degenerative brain disorder of unknown origin that causes progressive memory loss, motor deficits, and eventual death?
Alzheimer’s Disease
What are the Non-modifiable factors of Alzheimer’s?
But mostly a combination of genetics and environmental factors
What are the Modifiable factors of Alzheimer’s?
But mostly a combination of genetics and environmental factors
What happens at the early stages of Azheimer’s?
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
What are the early signs of Alzheimer’s?
What do these usually progress to?
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
Name the symptoms of Alzheimer’s:
At early
Middle
Late stages
Name a specific advanced stage of Azheimer’s:
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)
What causes brain dysfunction associated with Alzheimer’s?
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.
Name the 2 main types of Azheimer’s:
Early-onset
Hereditary
<5% cases
<60 -65 yrs under age of 65 (rarer type)
Late-onset
Majority cases
> recieving diagnosis over 60-65 yrs
Early-onset of Alzheimer’s which is hereditary and diagnosed under the age of 65 is cause by?
Early onset AD
Caused by gene mutations on chromosomes
What does it mean when the early onset of Alzheimer’s has Autosomal dominant inheritance?
If one of these mutated genes is inherited from a parent – person will almost always develop early onset AD
(Rarest form of A)
The late onset Alzheimer’s still has some genetic risk factors involved such as Apolipoprotein E (apoE).
Explain it’s relevance:
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)
Which allele of ApoE increases risk of developing AD (does not cause AD)?
E4
What are Alleles?
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.
Late onset AD
Most cases of AD are sporadic. What does this mean?
(i.e. not hereditary)
What causes b-amyloid accumulation?
Head injury, infections, excessive alcohol or other drugs, exposure to toxic substances, lifestyle factors
Brain atrophy
Brains between groups of patients with/without Alzheimer’s
should be age-matched due to the natural aging process of brain changing.
Brain atrophy:
What will patients with Alzheimer’s brain look like on an MRI scan?
Severe degeneration of the
hippocampus, cerebral cortex and ventricular enlargement
What will patients with Alzheimer’s brain look like at a cellular level?
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
Cellular Level Features:
What are the normal functions of b-amyloid (Ab)
mostly short form, soluble, circulate in CSF/blood
activator of kinase enzymes
protects against oxidative stress
regulation of cholesterol transport
anti-microbial actions
Cellular Level Features:
What are the ABnormal functions of b-amyloid (Ab) for patients with Alzheimer’s disease?
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
Synaptic loss:
Name the selective neurotransmitter systems that could be depleted by Alzheimer’s .
Depletion of selective neurotransmitter systems:
Acetylcholine (Ach)
Glutamate
Serotonin
Noradrenaline
Name Psychological (non-pharmacological) approaches to treating Alzheimer’s
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
Care giving of Alzheimer’s:
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!
Which types of drugs are prescribed to those with Alzheimer’s?
Cholinergic drugs
Eg. Aricept, donezepil, rivastigmine, galantamine
Nearly every drug currently licensed for AD = cholinesterase inhibitor (ChEI)
What do Cholinergic drugs do?
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
Name the Glutamate receptor antagonist which is prescribed for patients with AD:
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
What are the treatment approaches in development?
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
What are naturally occurring molecules, genes, or characteristics by which a particular pathological or physiological process, disease can be identified?
Biomarkers
Where are Biomarkers found?
Found in blood, other body fluids, organs and tissues
What is the function of Biomarkers?
Can track healthy functioning,
diagnose disease,
monitor response to treatment,
identify health risks
(e.g. high cholesterol/high blood pressure for cardiac disease)
How are Biomarkers Specific to Alzheimer’s Disease?
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
