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

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O'Callaghan, Claire  ORCID logo
Hezemans, Frank H 
Holland, Negin 

BACKGROUND: Neurodegeneration 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. OBJECTIVES: This 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. METHODS: Twenty-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. RESULTS: PSP 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. CONCLUSIONS: The 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.


Funder: Department of Health; Id:

Funder: Biomedical Research Centre; Id:

Funder: Medical Research Council; Id:

Funder: Wellcome Trust; Id:

Funder: James S. McDonnell Foundation; Id:

Funder: Patrick Berthoud Charitable Trust; Id:

Funder: National Health and Medical Research Council; Id:

7 T magnetic resonance imaging, Parkinson's disease, apathy, cognition, locus coeruleus, magnetization-transfer imaging, noradrenaline, progressive supranuclear palsy, Apathy, Cognition, Humans, Locus Coeruleus, Magnetic Resonance Imaging, Parkinson Disease, Parkinsonian Disorders, Supranuclear Palsy, Progressive
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Mov Disord
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Medical Research Council (MR/P01271X/1)
Medical Research Council (MR/R007446/1)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Patrick Berthoud Charitable Trust (via Charities Aid Foundation) (Unknown)
Medical Research Council (MC_UU_00005/12)
Wellcome Trust (220258/Z/20/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)