Evidence for divergent cortical organisation in Parkinsons disease and Lewy Body Dementia

Abstract

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 used 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 Parkinsons with normal cognition (PD-NC), 62 Lewy body dementia (LBD)) and 23 controls. We found divergent structural gradient differences with cognitive impairment: PD-NC showed increased inter-regional differentiation, whilst LBD showed overall gradient distribution similar to controls despite widespread organisational differences at the regional level. We then assessed 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.