Cortical gray matter progression in idiopathic REM sleep behavior disorder and its relation to cognitive decline

Abstract

Background: Idiopathic Rapid eye movement sleep behavior disorder (IRBD) is recognized as the prodromal stage of the alpha-Synucleinopathies. Although some studies have addressed the characterization of brain structure in IRBD, little is known about its progression.

Objective: The present work aims at further characterizing gray matter progression throughout IRBD relative to normal aging and investigating how these changes are associated with cognitive decline.

Methods: Fourteen patients with polysomnography-confirmed IRBD and 18 age-matched healthy controls (HC) underwent neuropsychological, olfactory, motor, and T1-weighted MRI evaluation at baseline and follow-up. We compared the evolution of cortical thickness (CTh), subcortical volumes, smell, motor and cognitive performance in IRBD and HC after a mean of 1.6 years. FreeSurfer was used for CTh and volumetry preprocessing and analyses. The symmetrized percent of change (SPC) of the CTh was correlated with the SPC of motor and neuropsychological performance.

Results: IRBD and HC differed significantly in the cortical thinning progression in regions encompassing bilateral superior parietal and precuneus, the right cuneus, the left occipital pole and lateral orbitofrontal gyri (FWE corrected, p < 0.05). The Visual form discrimination test showed worse progression in the IRBD relative to HC, that was associated with gray matter loss in the right superior parietal and the left precuneus. Increasing motor signs in IRBD were related to cortical thinning mainly involving frontal regions, and late-onset IRBD was associated with cortical thinning involving posterior areas (FWE corrected, p < 0.05). Despite finding olfactory identification deficits in IRBD, results did not show decline over the disease course.

Conclusion: Progression in IRBD patients is characterized by parieto-occipital and orbitofrontal thinning and visuospatial loss. The cognitive decline in IRBD is associated with degeneration in parietal regions.

Keywords: Cortical thickness; IRBD; Longitudinal data; Olfactory dysfunction; Parkinson’s disease; Visuospatial functions.

Fig. 1

Vertex-wise symmetrized percent change (SPC) in cortical thickness. A. Time effect for IRBD and HC group, cold colors represent negative SPC (GM loss across time); B. Group-by-time interaction, warm colors depict those regions were IRBD present reduced SPC in comparison with HC over the course of the study. Results were obtained using Monte Carlo simulation with 10,000 iterations applied to cortical thickness maps to provide cluster-wise correction for multiple comparisons (FWE corrected, p-value < 0.05). Simulation was applied for negative time effects (time 2 < time 1), whereas, on group-by-time contrast, simulation was applied for absolute results. Sex was used as a covariate. Abbreviations: HC, healthy controls; IRBD, idiopathic REM sleep behavior disorder; L, left; R, right.

Fig. 2

Correlates of VFD changes. Vertex-wise symmetrized percent change (SPC) in cortical thickness correlations with SPC Visual form Discrimination (VFD) scores in IRBD group. Sex was used as a covariate. The scale bar shows P values (FWE corrected, p-value < 0.05).

Fig. 3

A. Vertex-wise symmetrized percent change (SPC) in cortical thickness correlations with SPC MDS-UPDRS-III (Movement Disorder Society Unified Parkinson’s Disease Rating Scale motor section. ); B. Vertex-wise SPC in cortical thickness correlations with age of IRBD onset. Sex was used as a covariate. The scale bar shows P values (FWE corrected, p-value < 0.05).