Transdiagnostic quantitative assessment of dementias using in vivo MRI and data-driven disease progression modelling: a case study in Alzheimer’s disease and dementia with Lewy bodies

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Abstract INTRODUCTION Alzheimer’s disease (AD) and Lewy body disease cause brain atrophy producing dementia syndromes with shared clinical symptoms. We hypothesise that those diseases present with differential atrophy patterns, thus making disease progression modelling methods useful for biological staging. METHODS Using features derived from magnetic resonance imaging (MRI) scans from six international cohorts, we applied disease progression subtype and stage modelling on brain volume data from patients across Alzheimer’s disease dementia (ADD) and dementia with Lewy bodies (DLB) diagnoses. We assessed clinical, biomarker, and histopathological associations with the discovered atrophy subtypes. RESULTS We identified three data-driven brain atrophy subtypes across syndromes that could support biologically informed diagnosis in vivo: Limbic, Cortico-Limbic, and Cortical. Clinical syndrome and post-mortem assessments aligned imperfectly, but plausibly, with subtype: Limbic (more AD), Cortical (more DLB), Cortico-Limbic (mixed). In particular, the Limbic and Cortico-Limbic subtypes showed higher amyloid and tau positivity, and worse memory impairment than the Cortical subtype. CONCLUSION Our novel data-driven transdiagnostic approach shows promise for supporting in vivo biological diagnosis and subtyping of patients using only a single-visit MRI.

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