Imaging Alzheimer's Disease Flashcards
What is a big risk factor for Alzheimer’s disease?
Age
What is Dementia?
Umbrella of the symptoms of memory impairment, behavioural aspect
What is the most common form of disease especially over 65?
Alzheimer’s
What happens to people under the age of 65?
The causes of dementia even out between early onset and genetic forms of Alzheimer’s and Frontal Temporal Dementia
What happens as you lose brain?
The ventricles expand to fill the space
What are the early places where typical Alzheimer’s disease is found?
Hippocampus and a lot of structures in the medial temporal lobe
What can imaging give?
A feature of cognitive decline of Dementia
What are the roles for imaging Alzheimer’s Disease?
- Diagnosis
- Differential Diagnosis
- Neuroscience
- Disease progression and modification
What is the diagnosis?
- Structural pathology (e.g. tumour)
- Normal vs pathological (non-specific): atrophy or white matter changes
- Predictive
What is neuroscience?
Understand the onset and evolution of degenerative dementias
What are the disease progression and modification?
- For clinical trials
- memory test
- cognitive test
- how are people functioning?
What did the patient William Utermohlen use?
Self-portraits to document his decline into dementia
He cannot function on a daily basis
What are the 3 large phase of the inexorable progress from a prolonged preclinical phase
- Pre-clinical
- Diagnosis
- Dementia
What is preclinical phase?
Try to identify the underlying pathology for symptoms that are occuring and try to clear that up
What is the diagnosis phase?
that it causes dysfunction and damage in the neurons to cell death – cause people to decline in memory symptoms, behavioural symptoms
What is full blown dementia?
Where people are unable to take care of themselves and global function is really impaired
What happens long before any transition into cognitive impairment?
There is a long slow build-up of amyloid plaque data that is visible on either CSF lumbar punctures or on PET
When is Tau detected?
Only after the amyloid
What does build up of pathology cause?
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
What are the clinicopathological correlation stages of AD?
- Trans-entorhinal
- Limbic
- Neocortical
What is Trans-entorhinal?
A small portion of medial temporal lobe and that tends to go first with limbic, hippocampal, amygdala and medial temporal lobe structures
What is medial temporal lobe associated with?
Episodic memory
What can we rule out for the diagnosis of AD?
- Vitamin D deficiency
- Tumour
- Hypertension/vascular
mitigated by lifestyle factors
Why is Diagnosis of AD important?
- For patient and families
- To rule out other causes (space occupying lesion)
- To guide treatment and research
What is differential diagnosis of dementia by prevalence?
- Alzheimer’s Disease
- Vascular Dementia
- Dementia with Lewy Bodies
- Frontotemporal Dementia
What is differential diagnosis of dementia by characteristic features?
- Prion diseases
- Progressive supranuclear palsy
- Huntington Disease
- Leukodystrophies, SCAs, CADASIL
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
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
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
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
What are the Consensus Guidelines?
- European Federation of Neurological Socities (EFNS)
2. American Academy of Neurology (ANN) guidelines on the investigation of dementia
What does the current clinical practice depend on?
Availability of resources
What are examples of the availability of resources?
- T2-w (FLAIR) to assess vascular and other pathology
- Volumetric T1-w imaging to assess atrophy pattern
- Diffusion for CJD
- Functional imaging to distinguish FTLD from AD
What is National Institute of Ageing?
- Alzheimer’s Association Research Framework
- For research purposes only
- Acknowledges increasing use of imaging and other biomarkers
- Separates biology from clinical syndrome
From pathology to neurodegeneration
- Protein misfolding and accumulation
- Neuronal loss in vulnerable networks
- Progressive atrophy
- Progressive symptoms
What does Alzheimer’s disease tend to be?
Symmetric atrophy
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
What is hippocampus in mild AD?
10-20% smaller than in controls
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
What is providing an additional factor in the hippocampal medial temporal love to add to atrophy rate?
TDP
Hard to detect in-vivo
What is Limbic-predominant age-related TDP-43 encephalopathy (LATE)?
- pathology-based criteria
- Clinically related to AD-dementia like symptoms that are more severe than expected for the amount of amyloid and tau pathology
- Often associated with hippocampal sclerosis
- 20-50% of individuals over age of 80
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
