TY - JOUR
T1 - Substantia nigra and locus coeruleus microstructural abnormalities in isolated rapid eye movement sleep behaviour disorder and Parkinson's disease
AU - Pasquini, Jacopo
AU - Firbank, Michael J
AU - Best, Laura
AU - Foster, Victoria
AU - Stewart, Charlotte
AU - Silani, Vincenzo
AU - Durcan, Rory
AU - Roberts, Gemma
AU - Petrides, George
AU - Ceravolo, Roberto
AU - Brooks, David J
AU - Anderson, Kirstie N
AU - Pavese, Nicola
N1 - © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2025
Y1 - 2025
N2 - Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson's disease (PD) and may show neuroimaging abnormalities before the onset of motor manifestations. The simultaneous, multimodal investigation of their microstructural abnormalities may provide useful insights on the spatial diffusion and tissue characteristics of neurodegeneration, and this may in turn help develop markers for disease-modifying clinical trials. Therefore, through neuromelanin-sensitive and diffusion MRI, we aimed to investigate microstructural abnormalities in those nuclei in isolated REM sleep behaviour disorder (iRBD) and PD. Fourteen participants with polysomnography-confirmed iRBD, 18 with PD and 18 healthy controls were scanned with structural, neuromelanin-sensitive and neurite orientation dispersion and density imaging (NODDI) MRI. iRBD participants also underwent dopamine transporter imaging. SN neuromelanin and NODDI diffusion parameters and LC neuromelanin signals were extracted. Motor and global cognitive assessments were also collected. iRBD and PD participants showed significantly reduced neuromelanin contrast in the LC middle section compared with healthy controls. PD also showed significantly reduced caudal LC and posterior SN neuromelanin signal. No differences in SN NODDI parameters were detected between iRBD and healthy controls. Five iRBD participants showed reduced striatal dopamine transporter. In the combined disease groups (iRBD and PD), significant associations were shown between SN neuromelanin signal and neurite density index (
r = -0.610, corr-
p = 0.001) and between SN neurite density index and free water fraction (
r = 0.417, corr-
p = 0.042). In the same group, motor scores were negatively associated with nigral neuromelanin signal (
r = -0.404, corr-
p = 0.044) and free water fraction (
r = 0.486, corr-
p = 0.018). In conclusion, iRBD participants showed significant neuromelanin loss in the LC, with a minority showing initial nigrostriatal dopaminergic abnormalities. Across the entire iRBD-PD spectrum, the association between SN neuromelanin signal loss, diffusion parameters and motor scores has the potential to capture different yet related aspects of SN degeneration.
AB - Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson's disease (PD) and may show neuroimaging abnormalities before the onset of motor manifestations. The simultaneous, multimodal investigation of their microstructural abnormalities may provide useful insights on the spatial diffusion and tissue characteristics of neurodegeneration, and this may in turn help develop markers for disease-modifying clinical trials. Therefore, through neuromelanin-sensitive and diffusion MRI, we aimed to investigate microstructural abnormalities in those nuclei in isolated REM sleep behaviour disorder (iRBD) and PD. Fourteen participants with polysomnography-confirmed iRBD, 18 with PD and 18 healthy controls were scanned with structural, neuromelanin-sensitive and neurite orientation dispersion and density imaging (NODDI) MRI. iRBD participants also underwent dopamine transporter imaging. SN neuromelanin and NODDI diffusion parameters and LC neuromelanin signals were extracted. Motor and global cognitive assessments were also collected. iRBD and PD participants showed significantly reduced neuromelanin contrast in the LC middle section compared with healthy controls. PD also showed significantly reduced caudal LC and posterior SN neuromelanin signal. No differences in SN NODDI parameters were detected between iRBD and healthy controls. Five iRBD participants showed reduced striatal dopamine transporter. In the combined disease groups (iRBD and PD), significant associations were shown between SN neuromelanin signal and neurite density index (
r = -0.610, corr-
p = 0.001) and between SN neurite density index and free water fraction (
r = 0.417, corr-
p = 0.042). In the same group, motor scores were negatively associated with nigral neuromelanin signal (
r = -0.404, corr-
p = 0.044) and free water fraction (
r = 0.486, corr-
p = 0.018). In conclusion, iRBD participants showed significant neuromelanin loss in the LC, with a minority showing initial nigrostriatal dopaminergic abnormalities. Across the entire iRBD-PD spectrum, the association between SN neuromelanin signal loss, diffusion parameters and motor scores has the potential to capture different yet related aspects of SN degeneration.
KW - NODDI
KW - iRBD
KW - locus coeruleus
KW - neuromelanin
KW - substantia nigra
UR - http://www.scopus.com/inward/record.url?scp=85217808923&partnerID=8YFLogxK
U2 - 10.1093/braincomms/fcaf023
DO - 10.1093/braincomms/fcaf023
M3 - Journal article
C2 - 39926608
SN - 2632-1297
VL - 7
SP - fcaf023
JO - Brain Communications
JF - Brain Communications
IS - 1
M1 - fcaf023
ER -