L10 Imaging Alzheimer's Disease

Question 1

where does the disease start in AD and where does it spread

Answer 1

in preclinical stage starts in trans-entorhinal to limbic to neocortical

Question 2

what are types of dementia

Answer 2

alzheimers
vascular
dementia with lewy bodies
frontotemporal

prion
progressive supranuclear palsy
huntingdon’s disease
leukodystrophies, SCAs, CADASIL

Question 3

with what imaging can we see cerebral perfusion and metabolism

Answer 3

SPECT
MRI perfusion and fMRI
FDG-PET

Question 4

what can you see with molecular imaging

Answer 4

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

Question 5

what imaging type is used in current clinical practice for AD

Answer 5

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

Question 6

what is purpose of the research framework

Answer 6

acknowledge increasing use of imaging and other biomarkers

separates biology from clinical syndrome

Question 7

what are the steps from pathology to neurodegeneration

Answer 7

protein misfolding and accumulation
neuronal loss in vulnerable networks
progressive atrophy
progressive symptoms

Question 8

what is AD characterised by

Answer 8

symmetrical atrophy with posterior greater than anterior loss

Question 9

what sites show early change in AD

Answer 9

medial temporal lobe
precuneus
posterior cingulate

Question 10

what % is the hippocampus smaller in patients than in controls

Answer 10

10-20%

Question 11

what does atrophy relate to

Answer 11

loss of neurons

Question 12

there is a high correlation between MRI volumetric measures and …

Answer 12

no. of neurons present

Question 13

what is hippocampla atrophy a risk factor for

Answer 13

progression for MCI –> AD

Question 14

what may be the earliest region in atrophy published by Devanand et al

Answer 14

entorhinal cortex - neurofibrillary tangles may first appear there before spreading to medial temporal lobe structures and then on neocortical association areas

Question 15

apart from ad where else is symmetrical hippocampal atrophy seen in

Answer 15

dementia with lewy bodies

Question 16

what is a reliable way to distinguish AD from DLB

Answer 16

PET using tracers binding to amyloid and dopamine transporter uptake

Question 17

what focal atrophy patterns have positive/negative predictive value for FTLD /AD

Answer 17

FTLD +VE

AD -VE

Question 18

what is TDP-43 pathology related to

Answer 18

increased hippocampal atrophy rates in addition to f tau and amyloid status

Question 19

what do tau negative subjects show that separate them from tau positive shown in Josephs et al

Answer 19

show FDG pattern that results in a simple ratio of inferior to medial temporal lobes on the FDG image

Question 20

what is LATE and what is it associated with

what % in what age group

Answer 20

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

Question 21

what is the most used functional imaging and what can it show comparing AD to FTLD

Answer 21

PET using radiolabelled glucose

pattern of hypo metabolism different in FTD than AD, more frontal, less parietal

Question 22

what have studies such as Klunk and Mathis, Rowe, Nelissen, Rabinovici shown in AD compared to controls

Answer 22

increased level of amyloid binding

Question 23

in what MCI subjects does amyloid binding increase in

Answer 23

subjects who progress to AD

Question 24

in ADNI data used to track the spread of amyloid deposition, what does the analysis show of areas with amyloid

Answer 24

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

Question 25

what does spatiotemporal distribution of beta-amyloid in Alzheimer's disease results from

Answer 25

heterogeneous regional carrying capacities

Question 26

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

Answer 26

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

Question 27

what does tau-PET imaging with 11^C-PBBR show

Answer 27

medial temporal lobe shows no to little amyloid binding to in AD

Question 28

the pattern of amyloid deposition does not associate strongly with ...

Answer 28

patterns of atrophy and glucose hypometabolism

Question 29

the pattern of tau deposition does associate strongly with

Answer 29

patterns of atrophy and glucose hypometabolism

Question 30

what are tau-PET limitations

Answer 30

- 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

Question 31

what staging does the spread of tau pathology follow

Answer 31

Braak

Question 32

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

Answer 32

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

Question 33

what is a reliable biomarker to track the disease

Answer 33

measure the rate of loss over multiple scans from the same individual

Question 34

what is the % of atrophy rates per year in control compared to AD and what are the volumes for brain, ventricle, hippocampus

Answer 34

``` Brain: 1000 ml Ventricle: 40ml Hippocampus: 2-5ml B: 0.3% / 2% V: 1ml / 5ml H: 0.6% / 4% ```

Question 35

why may one scan not be enough

Answer 35

atrophy overlaps with aging

Question 36

what happens in registration

Answer 36

a transform that maps one scan onto another by matching image features and voxel gray level. uses all information within complex brain structure

Question 37

what is boundary shift integrsl

Answer 37

integrating shifts in intensity differences at brain boundary require highly accurate alignment and consistent imaging protocols and quality

Question 38

how is atrophy measurement through non-rigid registration

Answer 38

neurodegeneration involves structural readjustments as well as tissue loss model volume changes by warping one image to match another

Question 39

why do drug trials require a primary endpoint

Answer 39

to see if patient feels functions or survices

Question 40

what do atrophy measures show and how changing helps

Answer 40

atrophy measures show the underlying disease process. atrophy measures changing would help prove disease modification if atrophy was slowed with symptomatic benefit

Question 41

what do primary endpoints in AD trials measure

Answer 41

function

Question 42

what do imaging endpoints for AD trials require

Answer 42

smaller sample sizes

Question 43

in what clinical trial were there clear reductions in clinical decline with high dose aducanumab

Answer 43

EMERGE

Question 44

in what clinical trials were there clear reductions in amyloid PET with high dose aducanumab

Answer 44

EMERGE | ENGAGE

Question 45

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?

Answer 45

need to go through