Objective: To identify progressive structural and functional imaging alterations in a longitudinal cohort of patients with isolated rapid eye movement sleep behavior disorder (iRBD).

Background: Isolated RBD is now recognized as a prodrome of Parkinson’s Disease and Lewy body dementia. In addition to basal ganglia pathology, subcortical structures including the cholinergic basal forebrain and the noradrenergic locus coeruleus have been proposed to underlie cognitive and neuropsychiatric symptoms. Structural and functional MRI can provide insight into early pathological changes associated with iRBD disease progression for identifying biomarkers of disease conversion.

Method: Structural and functional MRI data was collected from 19 age-matched healthy controls and 21 iRBD patients of which 15 underwent repeat assessment and imaging over a 4-year period. Participants underwent clinical and neuropsychological assessments. Volume-based morphometry and seed based functional connectivity (FC) were analysed using the CAT12 and SPM toolbox on MATLAB. Statistical analysis included general linear models, repeated measures ANOVAs and correlation analysis corrected for multiple comparisons (FDR<0.05).

Results: In baseline assessments, iRBD patients had increased FC between the Nucleus Basalis of Meynert (NBM) and the visual network, along with decreased volume in the NBM and inferior parietal lobule compared to controls (all p-values < 0.05). Longitudinal follow-up on the iRBD patients indicated severe reduction in grey matter volume in the anterior cingulate cortex, visual cortex and amygdala (p < 0.05) compared to baseline. They also demonstrated increased thalamus-pedunculopontine nucleus FC (p = 0.015) and increased locus coeruleus-ventral attentional network FC (p = 0.015). Cognitive scores were negatively correlated with NBM and basal ganglia FC to the default mode, visual and attentional networks (p < 0.05). Patients who underwent disease conversion (1 PD; 2 DLB) had increased locus coeruleus FC to the dorsal attentional network (p = 0.035).

Conclusion: The results indicate that cholinergic pathways and regions responsible for visual processing are implicated early in iRBD. Additionally, abnormal FC in cholinergic and noradrenergic nuclei appears to be linked to the advancement of RBD, potentially serving as indicators for cognitive decline and disease transition in iRBD patients.

References: 1. Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019 Mar;142(3):744–59.
2. Postuma RB. Resting state MRI: a new marker of prodromal neurodegeneration? Brain. 2016 Aug 1;139(8):2106–8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-structural-and-functional-correlates-of-progression-in-isolated-rapid-eye-movement-sleep-behaviour-disorder/