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

Campabadal, Anna; Inguanzo, Anna; Segura, Bàrbara; Serradell, Mónica; Abós, Alexandra; Uribe, Carme; Gaig, Carles; Santamaría, Joan; Compta, Yaroslau; Bargalló, Núria; Junqué, C; Iranzo, Álex

doi:10.1016/j.nicl.2020.102421

Cited by 24 publications

(31 citation statements)

References 61 publications

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“…Decreased brain activity in the occipital lobe has also been reported to be associated with the delayed memory impairment [ 41 ]. A previous study has found that patients with idiopathic RBD showed decreased GMV in the occipital and parietal lobe, which were correlated with the visuospatial loss [ 42 ]. These results were similar to our study that the PD-RBD group showed reduced GMV and FC in the posterior regions than did those with PD-nRBD and significant correlation with the cognitive and motor impairment, indicating that the PD-RBD may correspond to more serious neurodegeneration and exhibit predictive value regarding the progression of motor symptoms and cognitive function, especially the visuospatial–executive function and delayed memory [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

Lang

Zhong

et al. 2021

Parkinson's Disease

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Objective. Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson’s disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods. Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results. Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion. Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial–executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

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Section: Discussionmentioning

confidence: 99%

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

Lang

Zhong

et al. 2021

Parkinson's Disease

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“…Isolated RBD is associated with brain volume and cortical thickness atrophy. [6][7][8][56][57][58][59][60][61] Patients also present with high rates of positivity to pathologic alpha-synuclein in tissue biopsies. [62][63][64][65] However, a mechanistic understanding of how alpha-synuclein pathology may relate to the patterns of brain atrophy in iRBD remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression

Rahayel

Tremblay

et al. 2021

Preprint

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Isolated REM sleep behaviour disorder (iRBD) is a synucleinopathy characterized by abnormal behaviours and vocalizations during REM sleep. Most iRBD patients develop dementia with Lewy bodies, Parkinson's disease, or multiple system atrophy over time. Patients with iRBD exhibit brain atrophy patterns that are reminiscent of those observed in overt synucleinopathies. However, the mechanisms linking brain atrophy to the underlying alpha-synuclein pathophysiology are poorly understood. Our objective was to investigate how the prion-like and regional vulnerability hypotheses of alpha-synuclein might explain brain atrophy in iRBD. Using a multicentric cohort of 182 polysomnography-confirmed iRBD patients who underwent T1-weighted MRI, we performed vertex-based cortical surface and deformation-based morphometry analyses to quantify brain atrophy in patients (67.8 years, 84% men) and 261 healthy controls (66.2 years, 75%) and investigated the morphological correlates of motor and cognitive functioning in iRBD. Next, we applied the agent-based Susceptible-Infected-Removed model (i.e., a computational model that simulates in silico the spread of pathologic alpha-synuclein based on structural connectivity and gene expression) and tested if it recreated atrophy in iRBD by statistically comparing simulated regional brain atrophy to the atrophy observed in patients. The impact of SNCA and GBA gene expression and brain connectivity was then evaluated by comparing the model fit to the one obtained in null models where either gene expression or connectivity was randomized. The results showed that iRBD patients present with cortical thinning and tissue deformation, which correlated with motor and cognitive functioning. Next, we found that the atrophy simulated based on brain connectivity and gene expression recreated cortical thinning (r=0.51, p=0.0007) and tissue deformation (r=0.52, p=0.0005) in patients, and that the connectome's architecture along with SNCA and GBA gene expression contributed to shaping atrophy in iRBD. We further demonstrated that the full agent-based model performed better than network measures or gene expression alone in recreating the atrophy pattern in iRBD. In summary, atrophy in iRBD is extensive, correlates with motor and cognitive functioning, and can be recreated using the dynamics of agent-based modelling, structural connectivity, and gene expression. These findings support the concepts that both prion-like spread and regional susceptibility account for the atrophy observed in prodromal synucleinopathies. Therefore, the agent-based Susceptible-Infected-Removed model may be a useful tool for testing hypotheses underlying neurodegenerative diseases and new therapies aimed at slowing or stopping the spread of alpha-synuclein pathology.

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“…For cortical gray matter, structural MRI can reveal cortical volume reductions of orbitofrontal cortex [43,49], dorsolateral frontal cortex [43,49], lingual gyrus [49], cingulate cortex [43,49], fusiform gyrus [46,49], and lateral occipital cortex [46,50] in iRBD patients compared with healthy controls. Atrophy of the parietal cortex, especially of the postcentral gyri and superior parietal cortex, is also seen in iRBD [46,50,51]. A longitudinal study, including a relatively small number of iRBD patients with evidence of phenoconversion to alpha-synucleinopathy [50] showed that iRBD patients who phenoconverted had widespread thinning in the left superior frontal, right precentral, and right lateral occipital gyri compared with nonconverters at the baseline MRI with a hazard ratio of 0.784 (sensitivity of 95% and specificity of 100%), suggesting potential use as prognostic biomarkers.…”

Section: Structural Mri Diffusion Tensor Imaging Functional Mri and N...mentioning

confidence: 99%

Imaging of sleep disorders in pre-Parkinsonian syndromes

Ota¹,

Kanel

Bohnen

2022

Current Opinion in Neurology

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Purpose of reviewNeuroimaging has been advanced in the last years and enabled clinicians to evaluate sleep disorders, especially isolated rapid eye movement sleep disorder (iRBD), which can be seen in alpha-synucleinopathies. iRBD is the best prodromal clinical marker for phenoconversion to these neurodegenerative diseases. This review aims to provide an update on advanced neuroimaging biomarkers in iRBD.Recent findingsAdvanced structural MRI techniques, such as diffusion tensor imaging and functional MRI, neuromelanin-sensitive MRI, and scintigraphic neuroimaging such as cholinergic PET, dopamine transporter imaging – single-photon emission computerized tomography, perfusional single-photon emission computerized tomography, and cardiac metaiodobenzylguanidine can provide diagnostic and prognostic imaging biomarkers for iRBD, in isolation and more robustly when combined.SummaryNew advanced neuroimaging can provide imaging biomarkers and aid in the appropriate clinical assessment and future therapeutic trials.

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

Cited by 24 publications

References 61 publications

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression

Imaging of sleep disorders in pre-Parkinsonian syndromes

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