HAI Book 2020 - Dec 18B

sing 18F-Florbetaben PET

Marquié2,3,4,5, Victor L. Villemagne6, Ángela
ongo3,5, Vincent Doré6, Norman Koglin1,2,
Santi7, Lluís Tárraga2,3,4,5, Andrew W.
byl8, Mercè Boada2,3,4,5

elgium
icades, Alzheimer Treatment and Research Center -
Spain
dades Neurodegenerativas (CIBERNED), Instituto de

Spain
University of Melbourne, Austin Health, Melbourne,

BB) SUVR abnormality cutoffs have been developed
and elderly Aβ-negative non-demented controls
ional research studies or interventional therapeutic
wer Aβ amount and extent may limit the use of
f this study was to develop and validate a FBB SUVR
to identify those subjects that will likely accumulate

f young healthy controls (YHC) (n=70, 27.6±5.1 y) as
ently, the SUVR cutoff was tested in two longitudinal
ine (SCD) (Fundació ACE Healthy Brain Initiative
Gómez et al. 2017) and (2) mild cognitively impaired
13). All subjects were quantified and SUVR derived
n: cerebellar gray matter) (Bullich et al. 2017) and
region: whole cerebellum (Klunk et al. 2015).

0.04 (SUVRcutoff=1.25) (MRI-based ROIs) and
regions in the SUVR continuum were defined as: Aβ-
on (“gray zone”) (1.25-1.48) and established Aβ
bjects in the “gray zone” (2.8±3.3 %/year (SCD),
y” (4.4±3.5 %/year (SCD), 1.1±2.1 %/year (MCI))
nner (p<0.05).

ptimal to detect early Aβ deposition and to identify

51

Cassady, Kaitlin

P6: Age-related neural dedifferentiati
related to beta-amyloid and tau patho

Kaitlin Cassady1, Jenna Adams1, Anne Maass2,
Jagust1,3

1Helen Wills Neuroscience Institute, UC Berkeley, Be
2German Center for Neurodegenerative Disease, Mag
3Lawrence Berkeley National Laboratory, Berkeley, C

Episodic memory loss is a hallmark cognitive dysfunc
which is associated with Aβ and tau accumulation. An
accumulation lead to memory decline. One possibility
is associated with reduced differentiation of large-scal
the finding that neural networks specialized for differe
‘differentiated’ (i.e., reduced within- and increased be
functional networks has been consistently reported in
impaired memory performance. In the present study, w
distinct episodic memory networks, the anterior-temp
associated with the accumulation of Aβ and tau. The A
recognition, and semantics and links anterolateral ento
lateral orbitofrontal and perirhinal cortex. The PM net
cognition and links posteromedial entorhinal cortex (p
precuneus, and parahippocampal cortex. We used rest
(FC) in the AT and PM networks in older (OA; N=87
25±4 years, 29F), and PIB-PET to measure Aβ and FT
age-related dedifferentiation (i.e., reduced within- and
these networks, with left alEC showing aberrant conn
(Fig-1). This increased connectivity was associated w
adults (r=.33, p=.04; Fig-2). These findings show that
aging by increasing cross-network connectivity betwe

5

ion of episodic memory networks is
ology in normal aging

Theresa Harrison1, Suzanne Baker3, William

erkeley, CA, US
gdeburg, Germany
CA, US
ction in normal aging and Alzheimer’s disease (AD),
n important open question is how Aβ and tau
y is that the accumulation of these protein aggregates
le neural networks. Neural dedifferentiation reflects
ent cognitive functions become less selective or
etween-network connectivity). Dedifferentiation of
the aging brain and has also been associated with
we investigated whether dedifferentiation in two
poral (AT) and posterior-medial (PM) networks is
AT network is related to memory for objects,
orhinal cortex (alEC) to ventral anterior temporal,
twork is related to context, retrieval, and spatial
pmEC) to retrosplenial, posterior-cingulate,
ting state fMRI to measure functional connectivity
7, 76±6 years, 55F) and younger adults (YA; N=55,
TP-PET to measure tau in OA. We found evidence for
d increased between-network FC with older age) in
nectivity to retrosplenial cortex in OA compared to YA
with greater retrosplenial tau in Aβ-positive older
t AD pathology disrupts the normal AT network in
een AT and PM network components.

52

Keywords: aging, dedifferentiation, anterior-tempora
5

al (AT), posterior-medial (PM), tau
53

Coomans, Emma M

P7: Tau pathology and synaptic loss a
disease in vivo: a combined [18F]florta

Emma M Coomans1, Sander CJ Verfaillie1, Emm
Golla1, Rik Ossenkoppele2,3, Wiep Scheper2,4,5,
Michael Ryan7, Robert C Schuit1, Albert D Win
Bart NM van Berckel1

1Department of Radiology & Nuclear Medicine, Amst
Amsterdam University Medical Center, Amsterdam, T
2Alzheimer Center Amsterdam, Department of Neurol
Amsterdam, Amsterdam University Medical Center, A
3Clinical Memory Research Unit, Lund University, Lu
4Department of Clinical Genetics, Amsterdam Neuros
University Medical Center, Amsterdam, The Netherla
5Center for Neurogenenomics and Cognitive Research
Science, Vrije Universiteit, Amsterdam, The Netherlan
6Department of Anaesthesiology, Vrije Universiteit Am
Amsterdam, The Netherlands
7Rodin Therapeutics, Boston, MA, US

Background: Synaptic loss, a pathological hallmark o
using the synaptic vesicle 2A (SV2A)-radiotracer [11C
binding in AD has previously been reported1, 2. It is cu
loss is associated with tau pathology in vivo.

Methods: Seven amyloid-positive AD subjects (age 6
from the Amsterdam Dementia Cohort3. All subjects u
arterial sampling and 130-min dynamic [18F]flortaucip
plasma input-derived) was obtained using the centrum
[18F]flortaucipir binding (BPND) was determined with
cerebellar gray matter). We performed generalized est
investigate associations between [11C]UCB-J and [18F
a priori defined temporal, parietal, frontal and occipita

Results: Across subjects and ROIs, higher [18F]flortau
DVR (β=-0.35, p<0.001) (Fig1). Within subjects 1, 2
[18F]flortaucipir BPND was associated with lower [11C]
trend (r=-0.57, p=0.004; r=-0.73, p<0.001; r=-0.46, p
contrast, within AD subjects 5, 6 and 7, who showed l
associated with higher [11C]UCB-J DVR (r=0.41, p=0
[18F]flortaucipir and [11C]UCB-J PET images are show

Conclusion: Across subjects, higher regional tau path
subjects, negative associations were observed when to
associations were observed when total tau levels were
to the occurrence of synaptic loss in response to tau pa

5

are closely associated in Alzheimer’s
aucipir and [11C]UCB-J PET study

ma E Wolters1,2, Hayel Tuncel1, Sandeep SV
Patrick Schober6, Steven P Sweeney7, J
ndhorst1, Philip Scheltens2, Ronald Boellaard1,

terdam Neuroscience, Vrije Universiteit Amsterdam,
The Netherlands
logy, Amsterdam Neuroscience, Vrije Universiteit
Amsterdam, The Netherlands
und, Sweden
science, Vrije Universiteit Amsterdam, Amsterdam
ands
h, Department of Functional Genomics, Faculty of
nds
msterdam, Amsterdam University Medical Center,

of Alzheimer’s disease (AD), can be measured in vivo
C]UCB-J. Indeed, reduced hippocampal SV2A-tracer
urrently unknown, however, to what extent synaptic

64.3±8.2; 3/7 female; MMSE 24.1±1.8) were included
underwent 60-min dynamic [11C]UCB-J PET with
pir PET. [11C]UCB-J distribution volume ratio (DVR,
m semi-ovale as reference region. Specific
receptor parametric mapping (reference region:
timating equation (GEE) and Spearman correlation to
F]flortaucipir across and within subjects in 12 bilateral
al region-of-interests (ROIs).

ucipir BPND was associated with lower [11C]UCB-J
and 4, who showed high tau levels, higher
]UCB-J DVR across ROIs; AD subject 3 showed a
p=0.02 and r=-0.39, p=0.06 respectively) (Fig2). In
low tau levels, higher [18F]flortaucipir BPND was
0.05; r=0.80, p<0.001; r=0.64, p=0.001 respectively).
wn for two AD subjects (Fig3).

hology was associated with synaptic loss. Within
otal tau levels were high, whereas positive
e low, possibly suggesting synaptic upregulation prior
athology.

54

5

55

5

56

Keywords: Tau, SV2A, Synaptic Density, Neuroimagin
5

ng, Alzheimer’s disease
57

Coomans, Emma

P8: Longitudinal dynamic [18F]florta
stage tau pathology in individuals with

Emma Coomans1, Denise Visser1, Rik Ossenkop
Timmers1,2, Emma E Wolters1,2, Hayel Tuncel1,
Windhorst1, Philip Scheltens2, Wiesje M van de

1Department of Radiology & Nuclear Medicine, Amst
Amsterdam University Medical Center, Amsterdam, T
2Alzheimer Center Amsterdam, Department of Neurol
Amsterdam, Amsterdam University Medical Center, A
3Clinical Memory Research Unit, Lund University, Lu
4Janssen Research & Development, Beerse, Belgium
5Department of Epidemiology and Biostatistics, Vrije
Medical Center, Amsterdam, The Netherlands

Background: Tau pathology is related to clinical prog
tau imaging in preclinical AD may help to identify ind
protocols allow for accurate quantitative measures of
to investigate whether individuals with subjective cog
measured using dynamic [18F]flortaucipir PET, over a

Methods: In an ongoing sub-study of the SCIENCe p
female, MMSE 29±1, 26% [18F]florbetapir PET positi
90-minute dynamic [18F]florbetapir PET at baseline an
baseline and 2.03±.01-year follow-up. [18F]flortaucipi
receptor parametric mapping (reference region: cerebe
overlapping regions-of-interest reflecting early (media
(neocortical) tau pathology. Repeated measures ANOV
the interaction effect of amyloid-β, amyloid-β status w

Results: A significant increase in medial temporal [18
p=0.033, reflecting an average 2-year increase from 0
[18F]flortaucipir BPND in the limbic and neocortical re
(p>0.05). Addition of amyloid status to the model rev
neocortical regions (p≤0.02), attributable to larger inc
individuals(Fig.2). Data collection is ongoing.

Conclusion: Over two years, quantitative imaging rev
tau pathology regions within SCD subjects. Individua
higher levels and larger increases in intermediate and
that amyloid-β facilitates the spread of tau.

5

aucipir PET reveals increased early
h subjective cognitive decline

ppele2,3, Sander CJ Verfaillie1, Tessa
, Mark E Schmidt4, Ronald Boellaard1, Albert D
er Flier2,5, Bart NM van Berckel1

terdam Neuroscience, Vrije Universiteit Amsterdam,
The Netherlands
logy, Amsterdam Neuroscience, Vrije Universiteit
Amsterdam, The Netherlands
und, Sweden

Universiteit Amsterdam, Amsterdam University

gression in Alzheimer’s disease (AD). Longitudinal
dividuals at risk of progression. Dynamic scanning
tracer retention over time. The aim of this study was
gnitive decline (SCD) show a change in tau pathology,
a time period of two years.

project, we included 31 SCD subjects (age 65±7, 45%
ive on visual read)(Table 1). All subjects underwent
nd 130-minute dynamic [18F]flortaucipir PET at
ir binding potential (BPND) was determined using
ellar gray matter) and extracted within three non-
al temporal), intermediate (limbic) and late stage
OVA, adjusted for age and sex, was used. To examine
was added to the model.

8F]flortaucipir BPND was observed, F(1,28)=5.001,
0.01 to 0.03 [18F]flortaucipir BPND(Fig.1).
egions did not significantly increase over time
vealed an interaction effect in the limbic and
creases in [18F]flortaucipir BPND in amyloid-β positive

vealed an increase in tau pathology only in early stage
als with higher amyloid-β load showed relatively

late stage tau pathology, supporting the hypothesis

58

5

59

Keywords: Tau, SCD, Neuroimaging, Longitudinal, A
6

Amyloid
60

DiFilippo, Alexandra

P9: Preliminary evaluation of synaptic
[11C]UCB-J across the cognitive spect

Alexandra DiFilippo1,2, Dhanabalan Murali1,2, G
Barnhart1, Jonathan Engle1, Tobey Betthauser1,
Christian1,2

1University of Wisconsin-Madison School of Medicine
2University of Wisconsin-Madison Waisman Center, M

Objectives: Synaptic pathology is integral for identify
although its identification is commonly performed pos
SV2A and serves as a proxy for in vivo analysis of sy
we are studying synaptic loss across the clinical and p
synaptic loss can serve as a sensitive marker of neurod
accumulation and cognitive decline.
Methods: [11C]UCB-J dynamic PET imaging was con
from the UW ADRC. Amyloid (A) and tau(T) status w
imaging. The participants included nine cognitively un
MCI (non-AD) A-/T-, and one non-AD dementia A-/
distribution volume ratios (DVR), calculated with Log
reference region. Region of interest analysis included
regions have previously been identified as having low
Results: There was only small variation in [11C]UCB
participants. Relative to the CU (A-/T-) DVR, lower [
MCI(A-/T-) and dementia (A-/T-) with DVR of 1.80,
reductions in DVR were only seen in the MCI and dem
respectively).

Conclusions: This preliminary work reveals reduction
of cognitive function. Ongoing, longitudinal studies w
between cognitive, amyloid, and tau status with [11C]U

Keywords: Alzheimer’s disease, UCB-J, SV2A

6

c vesicle protein SV2A imaging with
trum

Grace McKinney1, Nancy Davenport1, Todd
Sterling Johnson1, Barbara Bendlin1, Bradley

e and Public Health, Madison, WI, US
Madison, WI, US
ying many neurological and psychiatric disorders,
st-mortem. [11C]UCB-J is a PET tracer targeting
ynaptic density. As part of an ongoing investigation,
pathological spectrum of AD to examine if regional
degeneration in the context of plaque and tangle

nducted over 70 minutes in participants recruited
was determined from [11C]PiB and [18F]MK6240 PET
nimpaired (CU) A-/T-, one unimpaired A+/T+, one
/T-. [11C]UCB-J binding was assessed using
gan graphical analysis using the centrum semiovale as
the hippocampus and the entorhinal cortex as these
wer [11C]UCB-J binding in the AD population.
-J hippocampus DVR (1.95±0.08) in the CU(A-/T-)
[11C]UCB-J DVRs were measured in the CU(A+/T+),
1.56, 1.51 respectively. In the entorhinal cortex,
mentia participants (CU: 1.83±0.11 vs. 1.49, 1.45

ns in [11C]UCB-J in individuals across the spectrum
with larger sample sizes will investigate associations
UCB-J measured synaptic density.

61

Flores, Shaney

P10: Quantifying off-target skull bind

Shaney Flores1, Brian Gordon1,2, Yi Su4, Jon Ch
Adedokun1, Russ Hornbeck1, John Morris2,3, Ta

1Department of Radiology, Washington University in
2Knight Alzheimer’s Disease Research Center, , Wash
Louis, MO, US
3Department of Neurology, Washington University in
4Banner Alzheimer’s Institute, Phoenix, AZ, US
Background: Previous reports on tau PET using [18F]
choroid plexus and basal ganglia while anecdotal repo
discussed. We evaluated off-target flortaucipir skull b
cognitively normal, mildly cognitively impaired, or w
Methods: Head CT, flortaucipir (tau), florbetapir (am
acquired for 313 participants. Standard uptake value r
FreeSurfer defined regions of interest (ROI) using cer
used to define a skull ROI after removing non-skull re
image to calculate the average SUVr for the skull. Ind
using Gaussian mixture modeling. Flortaucipir skull b
including off-target flortaucipir regions, and florbetap
Results: High tau PET skull binding was observed in
occipital and temporal areas (see Figure 1).

6

ding in [18F]Flortaucipir PET studies

hristensen1, Aylin Dincer1, Adedamola
ammie Benzinger1,2

St. Louis School of Medicine, St. Louis, MO, US
hington University in St. Louis School of Medicine, St.
St. Louis School of Medicine, St. Louis, MO, US
]flortaucipir addressed off-target binding in the
orts of off-target skull binding have been minimally
binding in a cohort of older adults classified as
with Alzheimer’s disease (AD) dementia.
myloid) PET, and T1-weighted MR images were
ratios (SUVrs) were calculated voxel-wise and for
rebellar grey as a reference. Subject specific CTs were
elated bone and tissue and then applied to the SUVr
dividuals were classified as high and low skull binding
binding was correlated with several brain regions,
pir skull binding.
15.8% of the cohort with the greatest levels in

62

Tau PET skull binding did not correlate with either ca
target binding mechanism. Elevated skull binding was
flortaucipir SUVrs in amyloid- individuals (t(214)=-2
positively correlated with a summary measure of tauo
Figure 2). This indicates a potential false positive read

6

audate or choroid plexus, suggesting a unique off-
s significantly related to higher inferior temporal
2.83, p<.01), and flortaucipir skull binding was
opathy in amyloid- but not amyloid+ individuals (see
ding for elevated tau pathology.

63

Skull binding was positively correlated between florta

Discussion: Quantitative evidence confirms informal
This skull binding is a unique source of off-target bind
particularly in regions proximal to the skull.
Keywords: flortaucipir, non-specific binding, off-targ

6

aucipir and florbetapir (r=0.48, p<.001; see Figure 3).

reports of off-target skull binding with flortaucipir.
ding that can complicate analyses of tau PET images,
get binding, skull
64

Foster, Chris

P11: Influence of iron and beta-amylo
and hippocampal subfield volumes in

Chris Foster1, Kristen Kennedy1, Karen Rodrigu

1Center for Vital Longevity, School of Behavioral and
Dallas, TX, US
Age-related alterations to brain structure are regionall
structures, with overall hippocampus proper evidencin
contrast to entorhinal cortex, which evidences relative
AD patients and individuals at increased risk for AD,
displaying sensitivity to amyloid and tau which begin
also begins to accumulate in the brain early in the adu
amyloid, launching oxidative stress and a cascade of n
the independent and combined effects of beta-amyloid
weighted MRI) on aging of the hippocampal subfields
volumes in a sample of 71 cognitively normal older ad
combination of both elevated Aβ burden and greater i
volume, but not with HC subfield volumes in older ad
within-subject factor and age, iron, and Aβ as between
interaction among age, iron, Aβ, and MTL region, F(3
that the 3-way interaction was selective to the ERC, w
and ERC volume was only present in individuals with
not present in individuals with elevated Aβ, but lower
importance of studying Aβ in the context of other, pot
iron accumulation, as well as highlighting the potentia
earliest, preclinical stages of pathological aging.
Keywords: beta-amyloid, iron, entorhinal cortex, prec

6

oid deposition on entorhinal cortex
the aging brain

ue1

d Brain Science, The University of Texas at Dallas,

ly differential, even within the medial temporal
ng considerable vulnerability to even healthy aging, in
e resilience to the normal aging process. However, in
the ERC becomes a focus of neuropathology,
to form early in disease pathogenesis. Non-heme iron
ult lifespan and in animal models, interacts with beta-
neurotoxic processes. Here we sought to investigate
d (via Florbetapir) and iron content (via susceptibility-
s (Dentate/CA3, CA1-2, subiculum) and ERC
dults (Mage=68.01). We hypothesized that the
iron content would be associated with smaller ERC
dults. Mixed-effects models with MTL region as a
n-subjects factors indicated a significant four-way
3,189) = 5.24, p = .002. Post-hoc analyses revealed
where a significant negative association between age
h both elevated iron and Aβ. Further, this effect was
r levels of iron. These findings highlight the
tentially synergistic age-related brain factors, such as
al role for iron as an important contributor to the

clinical AD, hippocampal subfields

65

Lange, Catharina

P12: Voxel-wise relationships between
(WMH) and multimodal neuroimagin

Malo Gaubert1, Catharina Lange1,2, Antoine Gar
Gonneaud3, Robin de Flores3, Clémence Tomad
Vincent de La Sayette5,6, Gaël Chételat3, Mirank

1German Center for Neurodegenerative Diseases, Dre
2Dep. of Nuclear Medicine, Charité - Universitätsmed
Berlin, Humboldt-Universität zu Berlin, and Berlin In
3Inserm, Inserm UMR-S U1237, GIP Cyceron, Univer
4Lyon Institute for Elderly, Clinical and Research Me
1 University, Lyon, France
5Normandie Univ, UNICAEN, PSL Recherche Univer
Neuropsychologie et Imagerie de la Mémoire Humain
6CHU de Caen, Service de Neurologie, Caen, France

Background: White matter hyperintensities (WMH),
with increased risk of cognitive impairment and Alzhe
continuum suggest that increased WMH load may be
neurodegeneration in regions affected in AD.

Objective: To investigate relationships between AD n
distribution in older adults across the cognitive spectru

Methods: Participants (n=155) with normal cognition
impairment, and clinical AD were selected from the IM
(2) AV45-PET, (3) FDG-PET, and (4) T1 MRI. FLAI
segmentation-tool (Schmidt, 2017) to generate templa
were processed using standard pipelines including con
images. Mean AV45-SUVR, mean FDG-SUVR, and t
templates (Besson et al., 2015). Exploratory voxel-wis
neuroimaging biomarker as a predictor of regional WM

Results: Greater Aβ deposition, reduced glucose meta
associated with increased regional WMH across the en
Topographic distributions of these AD biomarker asso
(splenium) for all imaging modalities and periventricu
and GMV (Figure 1). When restricting our analysis to
relationships were maintained for FDG-SUVR and GM

Conclusion: Our findings corroborate that regional W
periventricular regions, are associated with AD neuroi
hypometabolism. These cross-sectional associations m
pathogenesis or, vice versa, contribution of AD pathol

6

n white matter hyperintensities
ng biomarkers of Alzheimer’s disease

rnier-Crussard3,4, Salma Bougacha3, Julie
desso3, Florence Mézenge3, Brigitte Landeau3,
ka Wirth1

esden, Germany
dizin Berlin, Corporate Member of Freie Universität
nstitute of Health, Berlin, Germany
rsité de Caen-Normandie, Caen, France
emory Centre of Lyon, Hospices Civils de Lyon, Lyon

rsités, EPHE, INSERM, U1077, CHU de Caen,
ne, GIP Cyceron, Caen, France

a marker of cerebrovascular disease, are associated
eimer’s disease (AD). Findings across the AD
related to increased Aβ burden and

neuroimaging biomarkers and voxel-wise WMH
um.

n, subjective cognitive decline, mild cognitive
MAP cohort with baseline scans of (1) FLAIR MRI,
IR images were analyzed with the lesion-
ate-space lesion probability maps. Other images (2-4)
nstruction of template-space PET-SUVR and GMV
total GMV were extracted within AD signature
se analysis were conducted with each AD
MH (Graff-Radford et al., 2019).

abolism, and reduced GMV in AD regions were
ntire cohort, adjusting for age, sex, and education.
ociated WMH included the corpus callosum
ular regions (posterior and anterior) for FDG-SUVR
o non-demented elderly (n=130), significant
MV.

WMH, including the posterior corpus callosum and
imaging biomarkers of Aβ burden and/or atrophy and
might reflect involvement of vascular damage in AD
logy to white matter damage.

66

Keywords: White matter hyperintensities, amyloid pat
6

thology, atrophy, hypometabolism
67

Gordon, Brian

P13: Beta-amyloid deposition and its a

Brian Gordon1, Manu Goyal1, Lars Couture1, Sh
Tammie Benzinger1, Andrei Vlassenko1

1Washington University in St. Louis, St. Louis, MO, U
Introduction: The deposition of beta-amyloid (Ab) in
prominent areas of accrual in posterior parietal region
this spatial topography. Aerobic glycolysis (AG) refer
AG are very plastic, and often identified as cortical hu
understanding brain metabolism can provide insight in
Methods: 622 participants between the ages of 30-100
were processed using Freesurfer into ROIs. Regional
to equalize the statistical distribution of values betwee
values. The normalized regional data from all scans w
resulting similarity matrix was reduced to two compon
cohort of younger adults (20-40 years, Figure 1).
Results: PC1 represented the regional pattern and wei
participants and is labeled the amyloid topography ind
Ab deposition) had spatial deposition patterns spatiall
adults. When examining ATI as a continuous measure
deposition became more similar to that of AG in youn
Ab was not as strong for other markers of metabolism
Conclusion: The current analyses indicate that the spa
the brain. In particular, there is a tight coupling betwe
neuronal activity tied to plasticity.

6

association with metabolism

haney Flores1, John Morris1, Marc Raichle1,

US
n the brain has a distinctive spatial pattern, with
ns. Less attention has been paid to the interpretation of
rs to the non-oxidative use of glucose. Areas high in
ubs in the brain. As Ab is tied to neuronal activity,
nto Ab accumulation.
0 underwent 1024 PET scans with 11C-PIB. PET data
SUVR values for each scan were quantile normalized
en scans while retaining the rank order of the regional
was analyzed then using multidimensional scaling. The
nents using PCA. A map of AG was defined in a

ights that explained the most variance in Ab across
dex (ATI). Older adults with a high ATI score (high
ly remarkably similar to AG defined in younger
e, as levels increased, the spatial pattern of Ab
ng adults. This same topographical relationship with
m such as CMRGlc, CMRO2, or CBF.
atial deposition of Ab mirrors metabolic properties in
een areas that develop Ab plaques and regions with

68

Keywords: amyloid, metabolism, PET, alzheimer, bra
6

ain
69

Goubran, Maged

P14: Amyloid binding is associated wi
microstructure in patients with signifi

Maged Goubran1, Miracle Ozzoude1, Sabrina A
Bocti4, Michael Borrie3, Howard Chertkow5, Ri
Alex Kiss1, Robert Jr. Laforce8, Michael D. Nos
D. Sahlas2, Christopher Scott1, Eric E. Smith9, V
Swartz1, Jean-Claude Tardif11, Alex Thiel10, Jea

1Sunnybrook Research Institute, Toronto, ON, Canada
2McMaster University, Hamilton, ON, Canada
3Western University, London, ON, Canada
4Université de Sherbrooke, Sherbrooke, QC, Canada
5Jewish General Hospital, Montreal, QC, Canada
6University of Calgary, Calgary, AB, Canada
7University of British Columbia, Vancouver, BC, Can
8Université Laval, Quebec City, QC, Canada
9Hotchkiss Brain Institute, Calgary, AB, Canada
10Montreal Neurological Institute, Montreal, QC, Can
11Montreal Heart Institute, Montreal, QC, Canada
12Rotman Research Institute, Toronto, ON, Canada

Background: Cognitive impairment involves degener
pathology, manifested as hyperintensities (WMH). W
edema. Non-specific WM binding of 18F-Florbetapir
white matter tracts. Our objective was to determine if
changes in a population with significant WMH.

Methods: 45 patients had baseline 3T MRI including
normal population with low WMH from ADNI was u
incorporated this in the Freesurfer pipeline. Standardi
pons was used as a measure for amyloid load. Multipl
performed, adjusting for age, between PET, DTI metr
multiple comparisons using false discovery rate.

7

ith markers of white matter
icant white matter disease

Adamo1, Katherine Zukotynski2, Christian
ichard Frayne6, Fuqiang Gao1, Robin Hsiung7,
seworthy2, Frank S. Prato3, Joel Ramirez1, Jim
Vesna Sossi7, Stephen Strother12, Richard
an-Paul Soucy10, Sandra E. Black1

a

nada
nada

ration in the grey matter, but also white matter
WMH may be reflective of demyelination or vasogenic

is thought to depend on the myelination status of the
amyloid deposition in WM is associated with DTI
DTI, 18F-Florbetapir PET/CT, and MMSE. A
used as a control group. We segmented WMH and
ized uptake value ratios (SUVr) normalized to the
le linear regression and partial correlations were
rics and WMH volumes. All tests were corrected for

70

Figure 1. Top row: Segmentation of WMH. Bottom r
segmentation.Results: White matter amyloid load wa
with MD (r=-0.35) in patients with high WMH load b
matter FA predicted WMH volumes (B=-5.69e04, p <
increased for patients with high WMH volumes comp
negatively correlated with MD in the left medial temp
> -0.40).

7

row: Freesurfer pipeline after incorporating the lesion
as correlated with FA (r=0.39) and inversely correlated
but not in ADNI controls. Normal appearing white
< 0.001). Normalized FA was decreased and MD
pared to controls (p=2.3e-20, p=0.00013). MMSE was
poral regions and SUVr in the left paracentral gyrus (r

71

Figure 2. Partial correlations of AV-45 SUVr and DT
both populations.Conclusion: This work supports the
may reflect microstructural integrity (myelination stat
will include analysis of free-water diffusion MRI.
Keywords: Amyloid PET, White matter disease, diffus

7

TI metrics, adjusting for age, in the white matter for
e hypothesis that non-specific WM amyloid binding
tus) in patients with high WMH load. Future work
sion MRI, microstructure, non-specific binding

72

Gunter, Jeffrey

P15: CSF dynamics explains discrepan

Jeffrey Gunter1, Matthew Senjem1, Petrice Cogs
Kantarci1, Prashanthi Vemuri1, Benjamin Elder4
Jones2, Michelle Mielke2, Neill Graff-Radford3,
Jack, Jr.1

1Department of Radiology, Mayo Clinic, Rochester, M
2Department of Neurology, Mayo Clinic, Rochester, M
3Department of Neurology, Mayo Clinic, Jacksonville
4Department of Neurosurgery, Mayo Clinic, Rocheste
Objective: Discordance of CSF aβ42 and amyloid PET
are abnormally low in NPH populations, possibly due
anatomic spatial pattern in shunt-responsive NPH inc
ventriculomegaly and enlarged Sylvian fissures (Figur
space Hydrocephalus (DESH). DESH features may be
a pattern matching score referred to as “computationa
was, do CSF and amyloid PET biomarkers differ and
in persons with a positive CDESH match?

Methods: CDESH scores were calculated from T1-w
of Aging (MCSA) and ADNI-GO/2. CSF aβ42, pTau
amyloid PET SUVR from PiB in MCSA and florbetap
tests were used to evaluate whether distributions of CS
positive and negative groups.

Results: The study included 843 (ADNI-2) and 829 (
7.0% and 7.7% of participants, respectively. Within e
different based on CDESH (p=0.13 and 0.70 respectiv
tau differed based on CDESH, all p-values <0.01 (Fig
aβ42 distributions differed based on CDESH, but the r

Conclusions: Distributions of absolute CSF analyte c
with and without CDESH; amyloid PET and ratios of
associated with lower absolute concentrations (possib
CSF ratios normalizes this phenomenon.

7

nt PET-CSF AD biomarkers

swell1, Christopher Schwarz1, Val Lowe1, Kejal
4, Hugo Botha2, Jonathan Graff-Radford2, David
, David Knopman2, Ronald Petersen2, Clifford

MN, US
MN, US
e, FL, US
er, MN, US
T measures is commonly reported. CSF biomarkers
e to dilution or impeded clearance. A common
cluding tight high convexity sulci in conjunction with
re 1) is Disproportionately Enlarged Subarachnoid-
e detected on MRI using machine learning, generating
al DESH” or “CDESH”. The question we addressed
is discordance of amyloid PET and CSF aβ42, higher

weighted MRI for individuals in the Mayo Clinic Study
and tTau were assessed using Elecsys assays with
pir in ADNI. Two-sample Kolmogorov-Smirnov
SF and PET biomarkers differed between CDESH

(MCSA) participants. A CDESH pattern was found in
each study amyloid PET SUVR distributions were not
vely). Within each study, CSF aβ42, pTau and total
gure 2). In amyloid PET negative participants CSF
ratios of CSF aβ42 to total tau did not (Figure 3).
concentrations differed systematically in participants
CSF markers did not. We conclude that CDESH is
bly by dilution or disordered CSF dynamics), but using

73

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74

Keywords: amyloid PET, Alzheimer’s disease, discord
7

dant biomarkers
75

Singh, Vikas

P16: Predicting future amyloid spread
longitudinal [C11]PiB-PET in preclini

Wei Hao1, Nicholas Vogt1, Zihang Meng1, Seon
Betthauser1, Bradley Christian1, Sterling Johnso

1University of Wisconsin-Madison, Madison, WI, US
2University of Pittsburgh, Pittsburgh, PA, US
Background: Predicting progression of Alzheimer’s d
individuals most likely to benefit from anti-amyloid th
predicts future amyloid burden based on baseline [C11
Method: Cognitively unimpaired participants from th
study (N=112, baseline age 67.6 ± 6.0 years) with at l
MRI were included. PiB DVR values were extracted f
accumulate amyloid. T1-weighted images were proces
‘graynet’ to construct single-subject level brain conne
model which uses both the individual-level MR derive
the amyloid burden measured at future visits.
A training set was used to estimate the parameters of t
from time-1 to time-2, informed by the individual-lev
the PiB measurements at time-3. In experiments, 90%
time-2 and the remaining served as the test set. A 10-f
Result: Fig. 3 shows the performance of our model on
from a linear estimate of the average group change be
accurate predictions of PiB-PET measurements in 69.
Conclusion: Our model captures propagation patterns
and PiB-PET) and performs much better than using th
Additional replication studies are planned.

7