HAI Book 2025 - Flipbook - Page 424
Ottoy, Julie
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Distinct spatiotemporal patterns of vascular disease in Alzheimer9s
disease subtypes
Julie Ottoy1, Eric Yin1, Min Su Kang1, Erin Gibson1, Andrew Clappison1, Ying Yang1, Katrina
Carver1, Nesrine Rahmouni2, Jenna Stevenson2, Stijn Servaes2, Joseph Therriault2, Tharick
Pascoal2, Jean-Paul Soucy3, Serge Gauthier2, Sandra Black1, Pedro Rosa-Neto2,3, Maged
Goubran1
1
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, CA
Translational Neuroimaging laboratory, McGill Centre for Studies in Aging, Montreal, QC, CA
3
Montreal Neurological Institute, McGill University, Montreal, QC, CA
2
Background: Alzheimer9s disease (AD) is a heterogeneous disorder that is often comorbid with cerebral small
vessel disease (SVD). However, the spatiotemporal patterns of SVD imaging markers remain not well understood.
Here, we evaluated 1) spatiotemporal effects of microstructural white matter injury on MRI-visible lesion
progression, and 2) whether distinct patient subtypes and stages exist based on regional SVD and AD biomarkers.
Methods: The longitudinal TRIAD cohort comprised cognitively normal, MCI, and AD dementia (baseline, y1, y2:
N=202, 100, 70). We quantified both global and regional imaging markers of microstructural injury (DTI-based free
water; fractional anisotropy; mean diffusivity in normal-appearing white matter) as well as MRI-visible lesions
(white matter hyperintensities 8WMH9; perivascular spaces 8PVS9). We studied baseline and longitudinal
associations of DTI-markers with WMH and PVS in (1) amyloid-negative (A´-) vs. A´+ individuals, and (2) subtypes
of individuals with distinct baseline SVD patterns, identified through the Subtype and Stage Inference (SuStaIn)
algorithm.
Results: At baseline, higher free water was associated with both higher WMH and PVS volume (P
