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Flashcards in Alzheimer's Disease Deck (101)
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1

Cognitive impairment feature in a number of neurodevelopmental, neurological and psychiatric disorders, including:

- Schizophrenia
- Depression
- ADHD
- Alzheimer's Disease
- Dementia
- Parkinson's Disease
- Mild Cognitive Impairment
- Fragile X
- Foetal Alcohol Spectrum Disorder

2

Cognitive impairment feature in a number of neurodevelopmental, neurological and psychiatric disorders, including:

- Schizophrenia
- Depression
- ADHD
- Alzheimer's Disease
- Dementia
- Parkinson's Disease
- Mild Cognitive Impairment
- Fragile X
- Foetal Alcohol Spectrum Disorder

3

What is MCI?

Patient complains of problems wit memory and this is confirmed by an informant.
Patient shows poor performance on formal memory tests, relative age and education matched healthy people.
Daily living and activities remain largely intact.
Do not meet the diagnostic criteria for Dementia.
Have an increased risk of developing Alzheimers Disease.
Around 50% or more of patients develop dementia within 5 years of MCI diagnosis.

4

What does ADAS- Cog stand for and what does it measure?

Alzheimers Disease Assessment Scale Cognitive Subscale. It is a test battery that measures the severity of impairment. Tests include memory & new learning, language and praxis.

5

We cannot currently predict which individuals will show the transition from MCI to dementia. What are some indications that can possible differentiate from those who will transition and those who will not?

- Imaging patterns of cortical thinning
- Serial MRI scans showing rate of change in brain atrophy
- APOE 4 genes can alter cholesterol transport and synaptic plasticity - carriers of gene may be more likely
- Poor performance on delayed recall tests

6

Treatments used for AD and dementia have been proven largely ineffective for MCI due to:



What MAY help?
_______ _________ required due to the risk of developing dementia

- heterogeneity of patients
- spectrum of aetiology and disorders
- multiple susceptibility genes linked to AD
- cognitive training
sensitive counselling

7

What are the risk factors for AD?

- age
- stroke
- genetic factors
- high BP
- head injury
- high cholesterol

8

Late onset AD occurs

> 65 years (most cases)

9

Early onset AD occurs

30-65 years (familial)

10

Alzheimers Disease: Clinical Picture - There is a progressive decline

- initially forgetful, difficulty finding words, leave tasks unfinished
- need help with basic activities, poor hygiene
- unable to recognise relatives or own reflection in mirror

11

Alzheimers Disease: Mood and behavioural disturbances

- irritable, emotional outbursts
- agitated, delusions of persecution (memory-related), disorientated
- inappropriate sexual advances towards strangers, use of coarse language, loss of impulse control

12

What is the diagnosis for AD? And what are the clinical problems with diagnosing?

Macroscopic examination of brain tissue after death
- problems differentiating from delirium or geriatric depression
- problems with referral due to fear or denial
- primarily based on memory dysfunction

13

In AD, there is a cognitive decline in:

- both implicit and explicit memory
- recognition memory
- STM including working memory
- semantic memory
- attention
- episodic memory
- anterograde amnesia
- retrograde amnesia

14

What is the pathology of AD?

- atrophy of the brain
- loss of cholinergic neurones from nucleus basalis of meynert

15

What does the nucleus basalis innervate?

- amygdala - emotion
- hippocampus & cortex - cognition

16

Loss of cholinergic neurones results in:

- widespread reduction in CHAT (choline acetyl transferase)
- depletion of nicotinic and presynaptic M2 muscarinic receptors (post synaptic receptors are usually preserved)

17

What is axonal transport?

The movement of mitochondria, lipids, synaptic vesicles, proteins and other organelles to and from the neurone's cell body. This occurs along a microtubule network.
Axons have no ribosomes and so rely on axonal transport for all their protein needs

18

What is Tau normally?

A soluble, microtubule-associated protein (MAP) which binds to microtubules and stabilises them.

19

Axonal transport relies on

microtubules acting as tracts which are stabilised by tau proteins.

20

Phosphorylation at crucial sites causes tau to

detach from microtubules, leading to microtubule breakdown and the accumulate of tau aggregated into paired helical filaments (PHFs)

21

Aggregations of tau proteins causes disruption of microtubules and subsequently the

normal transport of amyloid precursor protein (APP)

22

When tau threads become knotted and tangled up with another, they form

neurofibrillary tangles.

23

When tau threads become knotted and tangled up with another, they form ________ _______. When this happens, the microtubules...

neurofibrillary tangles.
disintegrate, collapsing the neurones transport system

24

When tau threads become knotted and tangled up with another, they form ________ _______. When this happens, the microtubules...
This may first result in

neurofibrillary tangles.
disintegrate, collapsing the neurones transport system
- malfunctions in communication between neurones and later neurodegeneration and cell death

25

What single gene is Tau encoded by? and on which chromosome?

MAPT
chromosome 17

26

____ protein isoforms are generated by alternative splicing of exons __, __ or ____

6
2
3
10

27

Tau isoforms can differ in

the number of tubulin binding domains (3 or 4 repeats located on C terminal half) and referred to 3R or 4R tau isoforms.

28

In AD, the tau isoforms involved are

3R and 4R

29

In frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) there are _____ isoforms

several

30

In AD, how many tau mutations are there?
However in FTDP-17 patients....
THEREFORE, tau pathology must be downstream of ____ in the neurodegenerative cascade.
There must be Amyloid beta _____ and ______ ways of.....

None
Tau mutations alone can cause neurodegeneration.
Amyloid beta
dependent
independent
causes tau aggregation