title: Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer's disease.
abstract: We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer's disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.
authors.affiliation: Department of Electrical and Computer Engineering, Agency for Science, Technology and Research-National University of Singapore Clinical Imaging Research Centre, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore 117599.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: Department of Electrical and Computer Engineering, Agency for Science, Technology and Research-National University of Singapore Clinical Imaging Research Centre, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore 117599.
authors.forename: Nanbo
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02138.
authors.forename: Mert R
authors.initials: MR
authors.lastname: Sabuncu
authors.affiliation: Department of Electrical and Computer Engineering, Agency for Science, Technology and Research-National University of Singapore Clinical Imaging Research Centre, Singapore Institute for Neurotechnology and Memory Networks Program, National University of Singapore, Singapore 117599; Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129; Centre for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore 169857 thomas.yeo@nus.edu.sg.
authors.forename: B T Thomas
authors.initials: BT
authors.lastname: Yeo
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology*; D001284:Atrophy; D001499:Bayes Theorem; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction; D003704:Dementia / Q000209:etiology / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors
keywords: Alzheimer’s disease heterogeneity; Alzheimer’s disease subtypes; mental disorder subtypes; unsupervised machine learning; voxel-based morphometry