Data-driven trajectories of atrophy explain clinical heterogeneity across Lewy body diseases
EBIOMEDICINE, cilt.131, ss.1-22, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 131
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.ebiom.2026.106400
- Dergi Adı: EBIOMEDICINE
- Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), EMBASE, MEDLINE, Directory of Open Access Journals
- Sayfa Sayıları: ss.1-22
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
Summary
Background
Lewy body diseases (LBD) collectively share α-synuclein Lewy pathology, yet present wide clinical heterogeneity, with overlapping motor and non-motor features and progression patterns that challenge traditional diagnostic boundaries.
Methods
To resolve this spatiotemporal heterogeneity at the biological level, we applied a data-driven atrophy progression framework to MRI data from 833 individuals across Parkinson’s disease, dementia with Lewy bodies, and prodromal isolated REM sleep behaviour disorder using the Subtype and Stage Inference algorithm.
Findings
Four transdiagnostic subtypes (A: Early cortico-limbic/late basal ganglia, B: Early basal ganglia/late limbic, C: Early temporo-limbic/late basal ganglia, and D: Early basal ganglia–cingulate/late cortex) emerged, each defined by a distinct spatiotemporal progression of atrophy that explained cognitive, motor, and psychiatric variability. An early cortico-limbic/late basal ganglia subtype represented a dementia-prone subtype across clinical diagnoses, with limbic involvement associating with the emergence of visual hallucinations.
Interpretation
These biologically relevant spatiotemporal atrophy subtypes provide an interpretable stratification of patients with LBD, with the potential to refine prognosis, improve clinical trial stratification, and guide precision therapeutic approaches.