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

Pietro Mattioli, Matteo Pardini, Francesco Famà, Nicola Girtler, Andrea Brugnolo, Beatrice Orso, Riccardo Meli, Laura Filippi, Stefano Grisanti, Federico Massa, Matteo Bauckneht, Alberto Miceli, Michele Terzaghi, Silvia Morbelli, Flavio Nobili, Dario Arnaldi

Research output: Contribution to journalArticlepeer-review


Purpose: To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD). Methods: 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. Results: 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. Conclusion: Our data suggest that cuneus/precuneus is a hub of a large functional network subserving cognitive function in iRBD.

Original languageEnglish
Pages (from-to)2834-2845
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Publication statusPublished - Aug 2021


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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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