MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Background. Dementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized by a wide heterogeneity of symptoms, which could be explained by the existence of distinct patterns of grey matter atrophy (GM).

Methods. We included 165 patients with probable DLB from the Mayo Clinic and 3 centers from the European DLB consortium. We performed cluster analysis based on GM volumes from 82 cortical, 12 subcortical, and 2 brainstem regions to identify subtypes. To further characterize the subtypes, we assessed between-group differences in MRI volumes, demographic, and clinical data as well as tau, β-amyloid and cerebrovascular biomarkers. Additionally, we evaluated their cognitive trajectories over three years of follow-up.

Results. We identified 3 DLB subtypes with different patterns of GM volume and clinical profiles: a subtype with cortical predominant low GM volumes, which included older patients with worse global cognition and faster cognitive decline over 3 years (n=49, 30%); a subtype with low GM volumes in fronto-occipital regions (n=76, 46%); and a subtype of younger patients with the highest cortical GM volumes, but proportionally lower GM volumes in basal ganglia and a higher frequency of cognitive fluctuations (n=40, 24%).

Conclusions. In this relatively large multi-center cohort, data-driven analysis on MRI revealed 3 distinct subtypes within probable DLB, which may have implications for clinical workout, research, and therapeutic decisions.