Cuneus atrophy and Parkinsonian phenoconversion in cognitively unimpaired patients with isolated REM sleep behavior disorder

Andreas Myhre Baun*, Alex Iranzo*, Miriam Højholt Terkelsen, Morten Gersel Stokholm, Kristian Stær, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Per Borghammer, Eduardo Tolosa, Simon Fristed Eskildsen, Nicola Pavese

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperComment/debate/letter to the editorResearchpeer-review

Abstract

Isolated rapid-eye-movement sleep behavior disorder (iRBD) is a strong predictor of Parkinson's disease and Dementia with Lewy bodies. Previous studies indicate that cortical atrophy in iRBD patients may be linked to cognitive impairment, but the pattern of atrophy is inconsistently reported. This study aimed to elucidate cortical atrophy patterns in a cognitively unimpaired iRBD cohort, focusing on regions associated with cognitive functions, particularly the cuneus/precuneus, and evaluated the predictive value for future phenoconversion. We conducted voxel-based morphometry and region of interest (ROI) analysis of structural MRI scans of 36 healthy controls and 19 iRBD patients, nine of whom also received a 3-year follow-up MRI scan. The iRBD patients were followed clinically for 8 years, and time-to-event analyses, using Cox regression, were performed based on baseline ROI volumes. The iRBD patients had lower gray-matter volume in the cuneus/precuneus region as well as in subcortical structures (caudate nuclei and putamen) compared to controls. Eight iRBD patients developed either Parkinson's disease (N = 4) or Dementia with Lewy bodies (N = 4) during the follow-up period. Time-to-event analyses showed that lower right cuneus volume was associated with a higher risk of phenoconversion to alpha-synuclein-linked Parkinsonism in the iRBD patients (Hazard ratio = 13.0, CI: 1.53-110), and correlated with shorter time to conversion. In addition, lower volumes of the bilateral precuneus trended to indicate a higher risk of phenoconversion. These findings suggest a potential predictive value of cuneus and precuneus volumes in identifying iRBD patients at risk of disease progression, even before the onset of cognitive impairment.

Original languageEnglish
Article number59
Book seriesJournal of Neurology
Volume272
Issue1
ISSN0939-1517
DOIs
Publication statusPublished - Jan 2025

Keywords

  • Aged
  • Atrophy/pathology
  • Cognitive Dysfunction/diagnostic imaging
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Lewy Body Disease/diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Parkinson Disease/diagnostic imaging
  • REM Sleep Behavior Disorder/diagnostic imaging
  • Brain atrophy
  • Lewy bodies
  • REM sleep behavior disorder
  • Voxel based morphometry
  • Parkinson’s disease
  • Dementia

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