L10 Imaging Alzheimer's Disease Flashcards
where does the disease start in AD and where does it spread
in preclinical stage starts in trans-entorhinal to limbic to neocortical
what are types of dementia
alzheimers
vascular
dementia with lewy bodies
frontotemporal
prion
progressive supranuclear palsy
huntingdon’s disease
leukodystrophies, SCAs, CADASIL
with what imaging can we see cerebral perfusion and metabolism
SPECT
MRI perfusion and fMRI
FDG-PET
what can you see with molecular imaging
PET: amyloid or tau
activated microglia
synaptic density
PET tracers can bind to amyloid and tau deposits - imaging the histological hallmarks of AD, and ligands that can assess specific neurotransmitter systems - such as the dopaminergic transporter uptake - preferentially affected in lewy body disease
what imaging type is used in current clinical practice for AD
t2 (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 purpose of the research framework
acknowledge increasing use of imaging and other biomarkers
separates biology from clinical syndrome
what are the steps from pathology to neurodegeneration
protein misfolding and accumulation
neuronal loss in vulnerable networks
progressive atrophy
progressive symptoms
what is AD characterised by
symmetrical atrophy with posterior greater than anterior loss
what sites show early change in AD
medial temporal lobe
precuneus
posterior cingulate
what % is the hippocampus smaller in patients than in controls
10-20%
what does atrophy relate to
loss of neurons
there is a high correlation between MRI volumetric measures and …
no. of neurons present
what is hippocampla atrophy a risk factor for
progression for MCI –> AD
what may be the earliest region in atrophy published by Devanand et al
entorhinal cortex - neurofibrillary tangles may first appear there before spreading to medial temporal lobe structures and then on neocortical association areas
apart from ad where else is symmetrical hippocampal atrophy seen in
dementia with lewy bodies
what is a reliable way to distinguish AD from DLB
PET using tracers binding to amyloid and dopamine transporter uptake
what focal atrophy patterns have positive/negative predictive value for FTLD /AD
FTLD +VE
AD -VE
what is TDP-43 pathology related to
increased hippocampal atrophy rates in addition to f tau and amyloid status
what do tau negative subjects show that separate them from tau positive shown in Josephs et al
show FDG pattern that results in a simple ratio of inferior to medial temporal lobes on the FDG image
what is LATE and what is it associated with
what % in what age group
limbic predominant age-related TDP-43 encephalopathy
clinically related to AD 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 80
what is the most used functional imaging and what can it show comparing AD to FTLD
PET using radiolabelled glucose
pattern of hypo metabolism different in FTD than AD, more frontal, less parietal
what have studies such as Klunk and Mathis, Rowe, Nelissen, Rabinovici shown in AD compared to controls
increased level of amyloid binding
in what MCI subjects does amyloid binding increase in
subjects who progress to AD
in ADNI data used to track the spread of amyloid deposition, what does the analysis show of areas with amyloid
first areas were inferior temporal lobe and anterior cingulate followed by precuneus, posterior cingulate and prefrontal cortex.
medial temporal and subcortical structures some of last to change
what does spatiotemporal distribution of beta-amyloid in Alzheimer’s disease results from
heterogeneous regional carrying capacities
in a graph of x axis-time and y axis SUVr. what is r,NS, T.50, K symbolise on a curve
which ones are regional and which ones are global
r - growth rate
NS - non-specific binding
T.50 - transition time from no to max binding
K - tissue carrying capacity
regional: K and NS
global: r and T.50
what does tau-PET imaging with 11^C-PBBR show
medial temporal lobe shows no to little amyloid binding to in AD
the pattern of amyloid deposition does not associate strongly with …
patterns of atrophy and glucose hypometabolism
the pattern of tau deposition does associate strongly with
patterns of atrophy and glucose hypometabolism
what are tau-PET limitations
- non-specific uptake in basal ganglia, thalamus, choroid plexus, likely telated to monoamine oxidase B
- increased uptake in non-tau pathologies (semantic dementia) and no uptake in some tau pathologies
what staging does the spread of tau pathology follow
Braak
the paper by Cho H Lee et al on predicted sequence of cortical tau and amyloid beta deposition shows what regions are positive in tau and amyloid interactions
tau : entorhinal cortex is positive before any other region becomes tau positive or amyloid positive
the parahippocampal gyrus, fusiform fyrus, amygdala and inferior temporal lobe are the next regions to turn tau positive
in amyloid: whole host of regions turn positive roughly at same time as tau
what is a reliable biomarker to track the disease
measure the rate of loss over multiple scans from the same individual
what is the % of atrophy rates per year in control compared to AD and what are the volumes for brain, ventricle, hippocampus
Brain: 1000 ml Ventricle: 40ml Hippocampus: 2-5ml B: 0.3% / 2% V: 1ml / 5ml H: 0.6% / 4%
why may one scan not be enough
atrophy overlaps with aging
what happens in registration
a transform that maps one scan onto another by matching image features and voxel gray level.
uses all information within complex brain structure
what is boundary shift integrsl
integrating shifts in intensity differences at brain boundary
require highly accurate alignment and consistent imaging protocols and quality
how is atrophy measurement through non-rigid registration
neurodegeneration involves structural readjustments as well as tissue loss
model volume changes by warping one image to match another
why do drug trials require a primary endpoint
to see if patient feels functions or survices
what do atrophy measures show and how changing helps
atrophy measures show the underlying disease process. atrophy measures changing would help prove disease modification if atrophy was slowed with symptomatic benefit
what do primary endpoints in AD trials measure
function
what do imaging endpoints for AD trials require
smaller sample sizes
in what clinical trial were there clear reductions in clinical decline with high dose aducanumab
EMERGE
in what clinical trials were there clear reductions in amyloid PET with high dose aducanumab
EMERGE
ENGAGE
Is the prevalence of dementia in the elderly population (e.g 70-80 years old)?
Your risk?
What are the major causes of dementia?
Where are the earliest sites of pathological involvement in AD – and how does it progress?
What are the characteristic features of AD on
CT
MRI
Functional imaging (PET/Spect)
Other imaging modalities
Roles of imaging?
need to go through
