Evidence for divergent cortical organisation in Parkinson’s disease and Lewy Body Dementia

Dementia is a defining feature of Lewy body disease: its timing and onset distinguish different clinical diagnoses, and its effect on quality of life is profound. However, it remains unclear whether processes leading to cognitive and motor symptoms in Lewy body disease differ. To clarify this, we use in-vivo neuroimaging to assess spatial gradients of inter-regional differences in structural and functional connectivity in 108 people across the Lewy body disease spectrum (46 Parkinson's with normal cognition (PD-NC), 62 Lewy body dementia (LBD)) and 23 controls. We show divergent structural gradient differences with cognitive impairment: PD-NC show increased inter-regional differentiation, whilst LBD show overall gradient distribution similar to controls despite widespread organisational differences at the regional level. We then assess cellular and molecular underpinnings of these organisational changes. We reveal similarities and also important differences in the drivers of cortical organisation between LBD and PD-NC, particularly in layer 4 excitatory neurons.