Grey matter microstructural alterations distinguish cognitive impairment in Lewy body diseases

INTRODUCTION. Despite widespread cortical involvement in Lewy body diseases, conventional grey matter MRI measures have limited sensitivity. Microstructural measures from diffusion MRI may be more sensitive to early changes. METHODS. We examined grey matter microstructure in 197 participants across the Lewy body diseases spectrum: 88 Lewy body dementia (LBD), 109 Parkinson's normal cognition (PD-NC), and 46 controls. We compared tissue-weighted neurite density (tNDI), orientation dispersion index (tODI), and free water fraction (FWF) cross-sectionally and longitudinally. We examined relationships between microstructure, disease severity and plasma p-tau217. RESULTS. LBD participants showed widespread cortical and subcortical tODI and FWF increases compared to controls and PD-NC, despite minimal atrophy. These changes correlated with cognitive (but not motor severity) and with p-tau217. In 100 Parkinson's patients followed-up over 3 years, cortical FWF increased in those developing cognitive decline. DISCUSSION. Microstructural measures capture early grey matter changes, offering a sensitive marker of grey matter integrity in Lewy body diseases.