HAI Book 2025 - Flipbook - Page 690
An, Gordon Zhaoqi
170
Assessing the generalizability of AD subtypes across diverse
cohorts: HABS-HD and ADNI
Gordon Zhaoqi An1,2, Brain Gordon2, Aristeidis Sotiras2, Peter Millar3, Sid O9Bryant4, Beau
Ances2,3, Karin Meeker4
1
Devision of Computational and Data Sciences at Washington University in St. Louis, St. Louis, MO, US
Mallinckrodt Institute of Radiology at Washington University in St. Louis, School of Medicine, St. Louis, MO, US
3
Department of Neurology at Washington University in St. Louis, School of Medicine, St. Louis, MO, US
4
Institute for Translational Research at University of North Texas Health Science Center, Fort Worth, TX, US
2
Background: Alzheimer9s disease and related dementias (ADRDs) present significant biological heterogeneity,
which influences clinical outcomes and treatment responses. However, current ADRD research has been
predominately conducted in non-Hispanic white cohorts, such as the Alzheimer9s Disease Neuroimaging Initiative
(ADNI), limiting the understanding of ADRD progression in diverse populations. The Health and Aging Brain Study 3
Health Disparities (HABS-HD), which includes Black/African American (AA), Hispanic (HIS), and non-Hispanic white
(NHW) participants, offers a broader sociodemographic perspective. This study aims to test the generalizability of
ADRD subtypes and progression patterns identified in ADNI to the more diverse HABS-HD cohort.
Methods: Structural MRI data from HABS-HD (AA n=588, HIS n=1005, NHW n=1009) and ADNI (n=864) cohorts were
processed using FreeSurfer to extract brain cortical thickness and hippocampal volume. The Subtype and Stage
Inference (SuStaIn) algorithm was then applied to both datasets to identify spatial atrophy subtypes and disease
stages. To compare subtypes between cohorts, Positional Variance Diagrams (PVDs) in Figure 1 were used to
visualize the variability and uncertainty in disease progression patterns derived by the model.
Results: SuStaIn identified three spatial atrophy subtypes and progression stages in HABS-HD and ADNI. HABSHD's PVD patterns aligned with ADNI's, revealing distinct progression patterns: subtype 1 was characterized by
initial degeneration of the hippocampus, followed by posterior and then anterior spread; subtype 2 began with
occipital atrophy, progressing to parietal regions; subtype 3 was characterized by initial frontal degeneration,
HAI2025 - 690
