TY - JOUR
T1 - Cuneus atrophy and Parkinsonian phenoconversion in cognitively unimpaired patients with isolated REM sleep behavior disorder
AU - Baun, Andreas Myhre
AU - Iranzo, Alex
AU - Terkelsen, Miriam Højholt
AU - Stokholm, Morten Gersel
AU - Stær, Kristian
AU - Serradell, Mónica
AU - Otto, Marit
AU - Svendsen, Kristina Bacher
AU - Garrido, Alicia
AU - Vilas, Dolores
AU - Santamaria, Joan
AU - Møller, Arne
AU - Gaig, Carles
AU - Brooks, David J
AU - Borghammer, Per
AU - Tolosa, Eduardo
AU - Eskildsen, Simon Fristed
AU - Pavese, Nicola
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - Aged
KW - Atrophy/pathology
KW - Cognitive Dysfunction/diagnostic imaging
KW - Disease Progression
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Lewy Body Disease/diagnostic imaging
KW - Magnetic Resonance Imaging
KW - Male
KW - Middle Aged
KW - Parkinson Disease/diagnostic imaging
KW - REM Sleep Behavior Disorder/diagnostic imaging
KW - Brain atrophy
KW - Lewy bodies
KW - REM sleep behavior disorder
KW - Voxel based morphometry
KW - Parkinson’s disease
KW - Dementia
UR - http://www.scopus.com/inward/record.url?scp=85212222282&partnerID=8YFLogxK
U2 - 10.1007/s00415-024-12762-x
DO - 10.1007/s00415-024-12762-x
M3 - Comment/debate/letter to the editor
C2 - 39680182
SN - 0939-1517
VL - 272
JO - Journal of Neurology
JF - Journal of Neurology
IS - 1
M1 - 59
ER -