Locus Coeruleus Integrity from 7T MRI Relates to Apathy and Cognition in Parkinson’s Disease and Progressive Supranuclear Palsy

Abstract:

Objective The loss of noradrenergic neurons in the locus coeruleus contributes to neuropsychiatric symptoms in both Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). This study aimed to characterise the spatial patterns of locus coeruleus pathological change in PD and PSP, and its relationship to cognitive and psychiatric symptoms. Methods Twenty-five patients meeting clinical criteria for idiopathic PD, fourteen probable PSP-Richardson’s syndrome and twenty-four age-matched healthy controls (HC) were recruited. All participants underwent clinical assessments for cognition and apathy, and high-resolution (0.08 mm 3 ) 7T-magnetisation-transfer imaging to measure LC integrity in vivo . To establish spatial patterns of locus coeruleus change, we obtained sub-region summaries of mean contrast ratios and significant locus coeruleus clusters using voxelwise analyses (family-wise-corrected p PD, right caudal locus coeruleus, 37 voxels; HC>PSP, bilateral caudal locus coeruleus, 206 voxels). PSP and PD patients showed similar levels of locus coeruleus degeneration relative to controls, but this was spatially more extensive in PSP. Across both groups, variability of locus coeruleus integrity was associated with cognitive performance (MoCA: 200 voxels; ACE-R: 70 voxels) and apathy (Apathy Scale: 99 voxels). Conclusions The relationship between locus coeruleus structure and non-motor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioural features in neurodegenerative disease.