Alzheimer's & CAA Research: T1:T2 Ratios & Amyloid-Beta Findings

L. Pålhaugen, J. Jarholm, S. Tecelao et al. Cerebral Circulation - Cognition and Behavior 9 (2025) 100407
Abstract ID: 144
Congress theme: NEW DIRECTIONS IN THE FIELD OF VASCULAR, BEHAV-
IORAL, AND COGNITIVE DISORDERS
Regional T1:T2 Ratios are Higher in Alzheimer’s Disease than Healthy Con-
trols and Cerebral Amyloid Angiopathy Patients
Cheryl R McCreary
a , ∗
, Andrew E Beaudin
a
, Richard Frayne
b
,Eric E Smith
a
a
Department of Clinical Neurosciences, Cumming School of Medicine, University of
Calgary
b
Department of Radiology, Cumming School of Medicine, University of Calgary
∗
Corresponding author.
E-mail address: [email protected]
Introduction: Cerebral amyloid angiopathy (CAA) is a small vessel
disease with b-amyloid accumulation in the walls of cerebral vessels.
The ratio of T1-weighted to T2-weighted magnetic resonance images
(T1:T2ratio) has been shown to improve sensitivity of detecting changes
in signal intensity associated with myelin content in both gray and white
matter (WM) and b-amyloid accumulation in gray matter (GM). In this
exploratory study, we compared regional T1:T2ratios between control
(CTRL), CAA, and AD groups to determine if regional T1:T2ratios are
higher in CAA.
Methods: Cross-sectional data from an ongoing longitudinal cohort
study (Functional Assessment of Vascular Reactivity: FAVR) were ana-
lyzed. CAA participants were diagnosed according to the Boston criteria.
3D T1-weighted and 2D T2-weighted images were bias corrected, skull
stripped, and co-registered to the MNI152 template prior to calculat-
ing the ratio images. Linear mixed effects models were used to compare
mean T1:T2ratios between groups and gray brain regions adjusting for
age and sex, using Tukey’s method to adjust for multiple post-hoc com-
parisons across 3 groups and 56 regions.
Results: Data for 62 CTRL, 48 CAA and 24 AD participants were an-
alyzed. No differences in regional T1:T2ratios were detected between
CTRL and CAA (p > 0.05 for all comparisons). However, AD had higher
T1:T2ratios than CTRL and CAA in the anterior temporal fusiform, pos-
terior temporal fusiform, putamen, and thalamus. AD also had higher
T1:T2ratios than CTRL in the lingual cortex and temporal occipital
fusiform cortex.
Conclusions: T1:T2ratios in both cortical and subcortical gray matter
regions were higher in AD than CTRL and CAA. Similar T1:T2ratios in
CTRL and CAA may be a consequence of b- amyloid localization to the
cerebral blood vessels rather than senile plaques, and/or lower concen-
tration of b-amyloid than in AD.
Keywords: Cerebral small vessel disease; Alzheimer Disease; Cerebral
amyloid angiopathy; Magnetic resonance imaging; Ageing
Figure Legend: Age- and sex-adjusted estimated mean differences for
gray matter regions with increased T1:T2ratios.
Abstract ID: 145
Congress theme: NEW DIRECTIONS IN THE FIELD OF VASCULAR, BEHAV-
IORAL, AND COGNITIVE DISORDERS
Amyloid- 𝛽40 Increases Over Time in Amyloid-Positive Individuals With Non-
Confluent Multispot WMHs
Lene Pålhaugen
a , ∗
, Jonas Jarholm
a
, Sandra Tecelao
a
, Bjørn-Eivind Kirsebom
b
,
Per Selnes
a
,Tormod Fladby
a
a
Department of Neurology, Akershus University Hospital, Lørenskog, Norway
b
Department of Neurology, University Hospital of North Norway, Tromsø, Norway
∗
Corresponding author.
E-mail address: [email protected]
Introduction: Cerebral amyloid angiopathy (CAA) is common in
Alzheimer’s disease (AD) and older individuals and increases the risk
of cognitive impairment. In CAA, amyloid beta (A 𝛽) deposits in lep-
tomeningeal and cortical vessels, containing more A 𝛽40 than A 𝛽42.
Cerebrospinal fluid (CSF) in established CAA shows reduced levels
of A 𝛽40 and A 𝛽42, while in AD patients only A 𝛽42 levels are re-
duced. Clearance of A 𝛽may be dysfunctional, causing a build-up of
A 𝛽in parenchymal plaques and vasculature. However, early pre-clinical
stages may show transient increases in soluble A 𝛽before parenchymal
and vascular trapping dominate.
The Boston criteria 2.0 for CAA incorporated subcortical white matter
hyperintensities (WMHs) in a multispot pattern, but fluid biomarker cor-
relates are unknown. Here we examine longitudinal changes in A 𝛽40 in
individuals with multispot WMHs.
Methods: Non-demented participants from the longitudinal Dementia
Disease Initiation (DDI) cohort underwent clinical examination, lumbar
puncture and MRI. Amyloid stage (A ± ) was based on CSF A 𝛽42/A 𝛽40 ra-
tio. WMH lesions were segmented and subcortical small round or ovoid
lesions were counted by automatic algorithms. WMHs were also visually
quantified using the Fazekas scale. We classified participants into:
(1) Few WMHs — Fazekas 0–1 and < 10 multispot lesions;
(2) Non-confluent multispot (NC-MS) WMHs — Fazekas 1 and ≥ 10 mul-
tispot lesions;
(3) Confluent multispot (C-MS) WMHs — Fazekas 2–3 and ≥ 10 mul-
tispot lesions.
We used linear mixed model regression to examine the differences in
A 𝛽40 with time between the three groups, repeating the analyses in A ±
amyloid subjects separately.
Results: We included 433 subjects (mean age 64.4, 286 female, median
follow-up time 2.4 years). In the NC-MS WMHs group, A 𝛽40 levels in-
creased significantly with time, and the time trajectory was significantly
different compared to the other two groups. These differences were am-
plified in A + and diminished in A- subjects (Figure 1).
Conclusions: These results lay the ground for future clearance hypothe-
ses:
The rise of A 𝛽40 in A + NC-MS cases suggests an early-stage amyloi-
dosis phenotype where reduced clearance is present but not yet out-
weighed by deposition, leading to net accumulation in CSF. This pattern
may reflect early vascular or perivascular involvement and warrants in-
vestigation of upstream mechanisms, including potential choroid plexus
changes.
37

N. Lemon, E. Canepa, R. Parodi-Rullan et al. Cerebral Circulation - Cognition and Behavior 9 (2025) 100407
Keywords: Alzheimer Disease; Cerebral amyloid angiopathy; White-
Matter hyperintensities; Biochemical markers; Neuroimaging
Figure Legend: Adjusted fixed effects plots of WMH group ∗ time inter-
action on CSF A 𝛽40. The "non-confluent multispot WMHs" group is the
reference group. Age and sex are covariates. Variables were centered
and scaled to mean 0 and standard deviation 1.
Abstract ID: 148
Congress theme: NEW DIRECTIONS IN THE FIELD OF VASCULAR, BEHAV-
IORAL, AND COGNITIVE DISORDERS
Assessing Graphomotor Information Processing Speed and Process-Based Be-
havior: The Rowan Digital Cancellation Test
Ileana De Anda-Duran
a , ∗
, Shirine Moukaled
a
, Jessica G. Woo
b
,
Vanessa Fonseca Lomeli
a
, Elaine M. Urbina
c
,Umayma Saifuddin
d
, Sabah Iqbal
d
,
Thomas Auriemma
e
, Ganesh Baliga
e
,David J. Libon
f
a
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane
University, New Orleans, LA, USA
b
Department of Pediatrics and Department of Environmental Health; University of
Cincinnati, Cincinnati, OH, USA
c
Department of Pediatrics; University of Cincinnati, Cincinnati, OH, USA
d
Department of Medicine, School of Osteopathic Medicine, Rowan University, Stratford,
NJ, USA
e
Department of Computer Science, Rowan University, Glassboro, NJ, USA
f
Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging,
Rowan- Virtua School of Osteopathic Medicine, Stratford, New Jersey, USA
∗
Corresponding author.
E-mail address: [email protected]
Introduction: The Rowan Digital Cancellation Tests (RDCT) is a suite of
three computerized tests varying in stimulus complexity —letters, sym-
bols, and mixed letter/symbol conditions. This study examined memory
clinic patients and evaluated how RDCT outcome measures dissociate
between diagnostic groups over four time epochs (30, 60, 90, and 120
seconds).
Methods: Ninety-eight patients (age = 73.20 ± 7.29;
education = 15.51 ± 3.26; 46.3% female) were recruited from the
Rowan University Memory Assessment Program (MAP). Cluster anal-
ysis classified participants into three groups: cognitively normal (CN;
n = 26, MMSE = 28.73 ± 1.07); mild cognitive impairment (MCI; n = 61,
MMSE = 26.45 ± 3.13); and dementia (DEM; n = 11, MMSE = 20.18 ± 4.57).
RDCTs were administered on a 13-inch iPad Pro in landscape orienta-
tion. Sixteen targets appeared per quadrant for all tests. In the digital
letter cancellation task, participants circled the letter “A ”; in the sym-
bol cancellation task, a designated geometric symbol; in the mixed con-
dition, participants alternated between letter and symbol targets. Two
primary outcome measures were analyzed: (1) correct hit/search time
ratio (0–1.0), reflecting accuracy adjusted for search efficiency; and (2)
mean drawing time (seconds) for correct targets.
Results: Analyses of the correct hit/search time ratio indicated that
CN participants consistently outperformed MCI and DEM groups across
nearly all tests and epochs (p < 0.050). At 120 seconds, all three groups
were differentiated on the letter, symbol, and mixed tests (CN > MCI >
DEM, p < 0.050). For mean drawing time, DEM participants were signif-
icantly slower than CN and MCI at 90 and 120 seconds across all test
conditions (p < 0.030).
Conclusions: The Rowan Digital Cancellation Tests are easy to admin-
ister, well tolerated, and capture performance dimensions not typically
available in standard assessments.
RDCT measures reliably distinguished between cognitively normal, MCI,
and dementia participants, particularly at longer time intervals. These
findings suggest that RDCTs may provide a sensitive and scalable ap-
proach for detecting early cognitive impairment and dementia in clinical
and research settings.
Keywords: Cognition; Neuropsychology; Dementia; Ageing; Memory
Figure Legend: Table 1
Abstract ID: 005
Congress theme: PATHOPHYSIOLOGY OF VCI
Mitochondrial carbonic anhydrase VB: a new target mediating cerebrovas-
cular dysfunction and clearance in CAA and Alzheimer’s disease.
Nicole Lemon, Elisa Canepa, Rebecca Parodi-Rullan, Roberto Guzman-Hernandez,
Rafael Vazquez-Torres, Marc Ilies, Silvia Fossati
∗
Temple University Lewis Katz School of Medicine, Philadelphia
∗
Corresponding author.
E-mail address: [email protected]
Introduction: Cerebral endothelial cell (cEC) stress, including that in-
duced by vascular amyloid 𝛽(A 𝛽) and tau deposits, is an early con-
tributor to cerebrovascular damage, blood- brain barrier (BBB) dysfunc-
tion and clearance impairment, precipitating neurodegeneration and
neuroinflammation processes in cerebral amyloid angiopathy (CAA),
Alzheimer’s disease (AD) and dementias. However, the cellular and
molecular mechanisms through which A 𝛽and tau drive cEC and BBB
dysfunction remain to be fully clarified, and possible therapeutic strate-
gies are sorely needed. Our lab aims to understand mitochondrial and
metabolic effects of aggregated A 𝛽and tau on the cerebral vessels, and
to discover and test novel potential therapeutic strategies against cere-
brovascular dysfunction and clearance impairment in the AD and CAA
brain. We have recently discovered that carbonic anhydrase (CA) inhi-
bition prevents cerebrovascular and neurovascular dysfunction, amelio-
rating clearance in CAA and AD models.
Methods: We analyzed how changes in metabolic, mitochondrial and
apoptotic processes mediate BBB dysfunction in human cECs monolay-
ers challenged with A 𝛽, tau, and in animal models cerebral amyloido-
38