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
Abstract ID: 145
Congress theme: NEW DIRECTIONS IN THE FIELD OF VASCULAR, BEHAVIORAL, AND COGNITIVE DISORDERS
Congress theme: NEW DIRECTIONS IN THE FIELD OF VASCULAR, BEHAVIORAL, AND COGNITIVE DISORDERS
Regional T1:T2 Ratios are Higher in Alzheimer’s Disease than Healthy Controls and Cerebral Amyloid Angiopathy Patients
Amyloid-𝛽40 Increases Over Time in Amyloid-Positive Individuals With NonConfluent Multispot WMHs
Cheryl R McCreary a,∗ , Andrew E Beaudin a , Richard Frayne b , Eric E Smith a
Lene Pålhaugen a,∗ , Jonas Jarholm a , Sandra Tecelao a , Bjørn-Eivind Kirsebom b ,
Per Selnes a , Tormod Fladby a
a Department of Clinical Neurosciences, Cumming School of Medicine, University of
Calgary
b Department of Radiology, Cumming School of Medicine, University of Calgary
a Department of Neurology, Akershus University Hospital, Lørenskog, Norway
∗ Corresponding author.
∗ Corresponding author.
E-mail address: [email protected]
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 analyzed. 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 calculating 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 comparisons across 3 groups and 56 regions.
Results: Data for 62 CTRL, 48 CAA and 24 AD participants were analyzed. 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, posterior 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 concentration of b-amyloid than in AD.
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 (A𝛽) deposits in leptomeningeal and cortical vessels, containing more A𝛽40 than A𝛽42.
Cerebrospinal fluid (CSF) in established CAA shows reduced levels
of A𝛽40 and A𝛽42, while in AD patients only A𝛽42 levels are reduced. Clearance of A𝛽 may be dysfunctional, causing a build-up of
A𝛽 in parenchymal plaques and vasculature. However, early pre-clinical
stages may show transient increases in soluble A𝛽 before 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 correlates are unknown. Here we examine longitudinal changes in A𝛽40 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 A𝛽42/A𝛽40 ratio. 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 multispot lesions;
(3) Confluent multispot (C-MS) WMHs — Fazekas 2–3 and ≥10 multispot lesions.
We used linear mixed model regression to examine the differences in
A𝛽40 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, A𝛽40 levels increased significantly with time, and the time trajectory was significantly
different compared to the other two groups. These differences were amplified in A+ and diminished in A- subjects (Figure 1).
Conclusions: These results lay the ground for future clearance hypotheses:
The rise of A𝛽40 in A+ NC-MS cases suggests an early-stage amyloidosis phenotype where reduced clearance is present but not yet outweighed by deposition, leading to net accumulation in CSF. This pattern
may reflect early vascular or perivascular involvement and warrants investigation of upstream mechanisms, including potential choroid plexus
changes.
b Department of Neurology, University Hospital of North Norway, Tromsø, Norway
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.
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N. Lemon, E. Canepa, R. Parodi-Rullan et al.
Cerebral Circulation - Cognition and Behavior 9 (2025) 100407
were differentiated on the letter, symbol, and mixed tests (CN > MCI >
DEM, p<0.050). For mean drawing time, DEM participants were significantly 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 administer, 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 approach for detecting early cognitive impairment and dementia in clinical
and research settings.
Keywords: Alzheimer Disease; Cerebral amyloid angiopathy; WhiteMatter hyperintensities; Biochemical markers; Neuroimaging
Keywords: Cognition; Neuropsychology; Dementia; Ageing; Memory
Figure Legend: Adjusted fixed effects plots of WMH group ∗ time interaction on CSF A𝛽40. 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, BEHAVIORAL, AND COGNITIVE DISORDERS
Assessing Graphomotor Information Processing Speed and Process-Based Behavior: 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
Figure Legend: Table 1
Abstract ID: 005
Congress theme: PATHOPHYSIOLOGY OF VCI
Mitochondrial carbonic anhydrase VB: a new target mediating cerebrovascular dysfunction and clearance in CAA and Alzheimer’s disease.
∗ Corresponding author.
E-mail address: [email protected]
Nicole Lemon, Elisa Canepa, Rebecca Parodi-Rullan, Roberto Guzman-Hernandez,
Rafael Vazquez-Torres, Marc Ilies, Silvia Fossati ∗
Introduction: The Rowan Digital Cancellation Tests (RDCT) is a suite of
three computerized tests varying in stimulus complexity—letters, symbols, 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 analysis 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 orientation. Sixteen targets appeared per quadrant for all tests. In the digital
letter cancellation task, participants circled the letter “A”; in the symbol cancellation task, a designated geometric symbol; in the mixed condition, 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
Temple University Lewis Katz School of Medicine, Philadelphia
∗ Corresponding author.
E-mail address: [email protected]
Introduction: Cerebral endothelial cell (cEC) stress, including that induced by vascular amyloid 𝛽 (A𝛽) and tau deposits, is an early contributor to cerebrovascular damage, blood- brain barrier (BBB) dysfunction 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 A𝛽 and tau drive cEC and BBB
dysfunction remain to be fully clarified, and possible therapeutic strategies are sorely needed. Our lab aims to understand mitochondrial and
metabolic effects of aggregated A𝛽 and tau on the cerebral vessels, and
to discover and test novel potential therapeutic strategies against cerebrovascular dysfunction and clearance impairment in the AD and CAA
brain. We have recently discovered that carbonic anhydrase (CA) inhibition prevents cerebrovascular and neurovascular dysfunction, ameliorating clearance in CAA and AD models.
Methods: We analyzed how changes in metabolic, mitochondrial and
apoptotic processes mediate BBB dysfunction in human cECs monolayers challenged with A𝛽, tau, and in animal models cerebral amyloido-
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