Subtyping and staging of Alzheimer's disease from routine structural MRI with PHASE-AD
Baumeister, H.; Luesebrink, F.; Kleineidam, L.; Hansen, N.; Schmid, M.; Moscoso, A.; Leuzy, A.; Mastenbroek, S. E.; Groot, C.; Brosseron, F.; Ramirez, A.; Preis, L.; Gref, D.; Spruth, E. J.; Gemenetzi, M.; Altenstein, S.; Fliessbach, K.; Kimmich, O.; Schott, B. H.; Rostamzadeh, A.; Glanz, W.; Incesoy, E. I.; Butryn, M.; Janowitz, D.; Rauchmann, B.-S.; Mladinov, M.; Grazia, A.; Sodenkamp, S.; Stoecker, T.; Hetzer, S.; Dechent, P.; Stoecklein, S.; the Alzheimer's Disease Repository Without Borders Investigators, ; the Alzheimer's Disease Neuroimaging Initiative, ; the DELCODE study group, ; P
Show abstract
Structural MRI is routinely acquired in the clinical assessment of Alzheimer's disease, yet quantitative morphometric indices derived from these scans remain largely confined to research settings. Here we present PHASE-AD; a framework that translates such indices into clinically interpretable classifications of atrophy subtype and stage that jointly capture atrophy progression while accounting for inter-individual atrophy heterogeneity. PHASE-AD is trained on MRI scans from 8,415 participants and robustly captures limbic-predominant and hippocampal-sparing atrophy subtypes that were identified across seven independent datasets. Two cross-validation schemes revealed high robustness across different field strength and scanner manufacturer configurations. Atrophy classifications were associated with diverging clinical profiles and tau accumulation patterns. In prospective designs mirroring contemporary AD trials, they stratified longitudinal cognitive trajectories and outperformed semi-quantitative visual MRI assessments as a clinically established comparator. These findings support the integration of automated atrophy subtyping and staging into clinical practice and pharmacological trials.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer 98%
- Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease 97%
- AI-driven fusion of neurological work-up for assessment of biological Alzheimer’s disease 97%
Similar papers in this journal
- Default mode network tau predicts future clinical decline in atypical early Alzheimer’s disease 98%
- Tau-first subtype of Alzheimer's disease consistently identified across in vivo and post mortem studies 98%
- Glucose metabolism reflects local atrophy and tau pathology in symptomatic Alzheimer’s disease 97%
Similar papers in this journal
- Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease 97%
- Tau-PET and in vivo Braak-staging as a prognostic marker in Alzheimer’s disease 97%
- Head-to-head comparison between plasma p-tau217 and Flortaucipir-PET in amyloid-positive patients with cognitive impairment 96%