Cuneus/precuneus as a central hub for brain functional connectivity of mild cognitive impairment in idiopathic REM sleep behavior patients



To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD).


Thirty-nine consecutive iRBD patients, 17 with (RBD-MCI, 73.6±6.5 years), and 22 without (RBD-NC, 69.6±6.1 years) MCI underwent neuropsychological assessment, 18F-FDG-PET, and 123I-FP-CIT-SPECT as a marker of nigro-striatal dopaminergic function. Forty-two healthy subjects (69.6±8.5 years) were used as control for 18F-FDG-PET analysis. Brain metabolism was compared between the three groups by univariate analysis of variance. Post hoc comparison between RBD-MCI and RBD-NC was performed to investigate the presence of an MCI-related volume of interest (MCI-VOI). Brain functional connectivity was explored by interregional correlation analysis (IRCA), using the whole-brain normalized MCI-VOI uptake as the independent variable. Moreover, the MCI-VOI uptake was correlated with 123I-FP-CIT-SPECT specific-to-non displaceable binding ratios (SBR) and neuropsychological variables. Finally, the MCI-VOI white matter structural connectivity was analyzed by using a MRI-derived human atlas.


The MCI-VOI was characterized by a relative hypometabolism involving precuneus and cuneus (height threshold p<0.0001). IRCA (height threshold p<0.0001) revealed a brain functional network involving regions in frontal, temporal, parietal, and occipital lobes, thalamus, caudate, and red nuclei in iRBD patients. In controls, the network was smaller and involved temporal, occipital, cingulate cortex, and cerebellum. Moreover, MCI-VOI metabolism was correlated with verbal memory (p=0.01), executive functions (p=0.0001), and nigro-putaminal SBR (p=0.005). Finally, MCI-VOI was involved in a white matter network including cingulate fasciculus and corpus callosum.


Our data suggest that cuneus/precuneus is a hub of a large functional network subserving cognitive function in iRBD.

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This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016).


This work was supported by grant from Italian Ministry of Health - Italian Neuroscience network (RIN).

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Correspondence to Pietro Mattioli.

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Conflict of interest

Matteo Pardini receives research support from Novartis and Nutricia, received fees from Novartis, Merck, and Biogen. Silvia Morbelli received speaking honoraria from G.E. healthcare. Flavio Nobili received fees from BIAL for consultation, from G.E. healthcare for teaching talks, and from Roche for board participation. Dario Arnaldi received fees from Fidia for lectures and board participation. All other authors declare no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by local ethics committee of the Istituto Nazionale per la Ricerca sul Cancro-IST, IRCCS San Martino polyclinic Hospital on May 31, 2013, (no. 703).

Informed consent

Informed consent was obtained from all individual participants included in the study. The results of all the performed exams have been provided to the patients. Patients have been informed of the risk of phenoconversion, according to the “full disclosure” approach [63] and information regarding the strategies to minimize the neurodegeneration risk were provided [63].

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Mattioli, P., Pardini, M., Famà, F. et al. Cuneus/precuneus as a central hub for brain functional connectivity of mild cognitive impairment in idiopathic REM sleep behavior patients. Eur J Nucl Med Mol Imaging (2021).

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  • Rapid eye movement sleep behavior disorder (RBD)
  • Parkinson’s disease
  • Synucleinopathy
  • 18F-FDG-PET
  • Mild cognitive impairment (MCI)