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C3 CLINICAL > Imaging Alzheimer's Disease > Flashcards

Imaging Alzheimer's Disease Flashcards

1
Q

What is a big risk factor for Alzheimer’s disease?

A

Age

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2
Q

What is Dementia?

A

Umbrella of the symptoms of memory impairment, behavioural aspect

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3
Q

What is the most common form of disease especially over 65?

A

Alzheimer’s

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4
Q

What happens to people under the age of 65?

A

The causes of dementia even out between early onset and genetic forms of Alzheimer’s and Frontal Temporal Dementia

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5
Q

What happens as you lose brain?

A

The ventricles expand to fill the space

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6
Q

What are the early places where typical Alzheimer’s disease is found?

A

Hippocampus and a lot of structures in the medial temporal lobe

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7
Q

What can imaging give?

A

A feature of cognitive decline of Dementia

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8
Q

What are the roles for imaging Alzheimer’s Disease?

A
  1. Diagnosis
  2. Differential Diagnosis
  3. Neuroscience
  4. Disease progression and modification
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9
Q

What is the diagnosis?

A
  1. Structural pathology (e.g. tumour)
  2. Normal vs pathological (non-specific): atrophy or white matter changes
  3. Predictive
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10
Q

What is neuroscience?

A

Understand the onset and evolution of degenerative dementias

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11
Q

What are the disease progression and modification?

A
  1. For clinical trials
    - memory test
    - cognitive test
    - how are people functioning?
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12
Q

What did the patient William Utermohlen use?

A

Self-portraits to document his decline into dementia

He cannot function on a daily basis

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13
Q

What are the 3 large phase of the inexorable progress from a prolonged preclinical phase

A
  1. Pre-clinical
  2. Diagnosis
  3. Dementia
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14
Q

What is preclinical phase?

A

Try to identify the underlying pathology for symptoms that are occuring and try to clear that up

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15
Q

What is the diagnosis phase?

A

that it causes dysfunction and damage in the neurons to cell death – cause people to decline in memory symptoms, behavioural symptoms

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16
Q

What is full blown dementia?

A

Where people are unable to take care of themselves and global function is really impaired

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17
Q

What happens long before any transition into cognitive impairment?

A

There is a long slow build-up of amyloid plaque data that is visible on either CSF lumbar punctures or on PET

18
Q

When is Tau detected?

A

Only after the amyloid

19
Q

What does build up of pathology cause?

A

loss of brain cells and decrease in metabolism – poor functioning brain that continues to go up and that happens very proximal to when people start showing symptoms of mild cognitive impairments
• It doesn’t reach threshold to form diagnostic criteria and full-blown Alzheimer’s disease

20
Q

What are the clinicopathological correlation stages of AD?

A
  1. Trans-entorhinal
  2. Limbic
  3. Neocortical
21
Q

What is Trans-entorhinal?

A

A small portion of medial temporal lobe and that tends to go first with limbic, hippocampal, amygdala and medial temporal lobe structures

22
Q

What is medial temporal lobe associated with?

A

Episodic memory

23
Q

What can we rule out for the diagnosis of AD?

A
  1. Vitamin D deficiency
  2. Tumour
  3. Hypertension/vascular

mitigated by lifestyle factors

24
Q

Why is Diagnosis of AD important?

A
  1. For patient and families
  2. To rule out other causes (space occupying lesion)
  3. To guide treatment and research
25
What is differential diagnosis of dementia by prevalence?
1. Alzheimer's Disease 2. Vascular Dementia 3. Dementia with Lewy Bodies 4. Frontotemporal Dementia
26
What is differential diagnosis of dementia by characteristic features?
1. Prion diseases 2. Progressive supranuclear palsy 3. Huntington Disease 4. Leukodystrophies, SCAs, CADASIL
27
What is structural imaging used for?
Assess space occupying lesions, vascular damage and pattern of atrophy 1mm resolution of the brain - detailed measurement of volume of structures and where things are changing
28
Tissue microstructure
Understand where the tracts are going to different white matter areas from one area to the other and if those tracts are being impaired as part of the Alzheimer’s disease process
29
Metabolites and microbleeds
Look at a single voxel and get a spectroscopic signature and see what type of cellular components might be in this array in people with Alzheimer’s compared with control As well as small little microbleed deposits that are common in Alzheimer’s disease as a potential marker and also a predictor of how these people will handle drugs
30
Molecular Imaging
* Image where amyloid is being deposited – first sign of the Alzheimer’s disease pathology * Look at some new tracers – TAU – * Downstream measures that we hope are somewhere in between deposit initial pathology and when cells start to die and are observed on MRI and therefore look at synaptic density
31
What are the Consensus Guidelines?
1. European Federation of Neurological Socities (EFNS) | 2. American Academy of Neurology (ANN) guidelines on the investigation of dementia
32
What does the current clinical practice depend on?
Availability of resources
33
What are examples of the availability of resources?
1. T2-w (FLAIR) to assess vascular and other pathology 2. Volumetric T1-w imaging to assess atrophy pattern 3. Diffusion for CJD 4. Functional imaging to distinguish FTLD from AD
34
What is National Institute of Ageing?
1. Alzheimer's Association Research Framework 2. For research purposes only 3. Acknowledges increasing use of imaging and other biomarkers 4. Separates biology from clinical syndrome
35
From pathology to neurodegeneration
1. Protein misfolding and accumulation 2. Neuronal loss in vulnerable networks 3. Progressive atrophy 4. Progressive symptoms
36
What does Alzheimer's disease tend to be?
Symmetric atrophy
37
What is Alzhiemer's disease characterised by?
Symmetrical atrophy with posterior greater than anterior loss (cf FTLD) The medial temporal lobe, precuneus and posterior cingulate are sites of early change
38
What is hippocampus in mild AD?
10-20% smaller than in controls
39
What is a predictor for future decline?
Hippocampal atrophy • People who have hippocampi that are small tend to progress from MCI to AD • Hippocampal volume is definitely a risk factor
40
What is providing an additional factor in the hippocampal medial temporal love to add to atrophy rate?
TDP | Hard to detect in-vivo
41
What is Limbic-predominant age-related TDP-43 encephalopathy (LATE)?
1. pathology-based criteria 2. Clinically related to AD-dementia like symptoms that are more severe than expected for the amount of amyloid and tau pathology 3. Often associated with hippocampal sclerosis 4. 20-50% of individuals over age of 80
42
FDG-functional scan
* Where the brain is using the most fuel and glucose * In AD – hot colour means glucose being used * FTLD – the deficiency is more in the frontal than anterior-temporal areas

C3 CLINICAL (27 decks)

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