Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders.

Abstract

BackgroundNeurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging.ObjectivesThis study aimed to characterize the spatial patterns of LC pathological change in PD and PSP and the transdiagnostic relationship between LC signals and neuropsychiatric symptoms.MethodsTwenty‐five people with idiopathic PD, 14 people with probable PSP‐Richardson's syndrome, and 24 age‐matched healthy controls were recruited. Participants underwent clinical assessments and high‐resolution (0.08 mm3) 7 T‐magnetization‐transfer imaging to measure LC integrity in vivo. Spatial patterns of LC change were obtained using subregional mean contrast ratios and significant LC clusters; we further correlated the LC contrast with measures of apathy and cognition, using both mixed‐effect models and voxelwise analyses.ResultsPSP and PD groups showed significant LC degeneration in the caudal subregion relative to controls. Mixed‐effect models revealed a significant interaction between disease‐group and apathy‐related correlations with LC degeneration (β = 0.46, SE [standard error] = 0.17, F(1, 35) = 7.46, P = 0.01), driven by a strong correlation in PSP (β = −0.58, SE = 0.21, t(35) = −2.76, P = 0.009). Across both disease groups, voxelwise analyses indicated that lower LC integrity was associated with worse cognition and higher apathy scores.ConclusionsThe relationship between LC and nonmotor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioral features in neurodegenerative disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society