Abstract
This study aimed to explore the disrupted prefrontal cortex activity specific to patients with Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD) compared with those without and to further examine the associations between these alterations and neuropsychological measurements. Ninety-six patients with early PD underwent both structural and functional MRI, and also neuropsychological assessments in the Parkinson's Progression Markers Initiative (PPMI) database. Of these, 46 patients who completed 1- and 3-year fMRI follow-up examinations were categorized as PD with probable RBD (PD-pRBD+) and without (PD-pRBD−). The left dorsolateral prefrontal cortex (DLPFC) seed-to-voxel functional connectivity analysis was conducted to evaluate the progressive neural alterations specific to PD-pRBD+ compared with PD-pRBD− over time. Furthermore, relationships between these alterations and neuropsychological performance were examined. Compared with patients with PD-pRBD−, patients with PD-pRBD+ initially exhibited connectivity deficits between the left DLPFC and the medial frontopolar cortex. Moreover, these patients further exhibited disrupted DLPFC connectivity in the lateral frontopolar cortex at the 3-year follow-up evaluation. Correlation analysis revealed that connectivity between the left DLPFC and frontopolar cortex was positively related to executive function in PD-pRBD+ after adjusting for nuisance variables. Progressive prefrontal cortex dysfunction associated with RBD in early PD may provide an effective subtype-specific biomarker of neurodegenerative progression, which may shed light on the neuropathological mechanisms underlying the clinical heterogeneity of this disease.
Highlights
Sleep disturbances are frequently experienced in patients with Parkinson’s disease (PD) (Fereshtehnejad et al, 2017; Jozwiak et al, 2017)
Posthoc comparisons revealed that significantly higher Hoehn and Yahr stages (p < 0.05) and levodopa equivalent daily dose (LEDD) (p < 0.05) were detected at the 3-year follow-up evaluation compared with baseline in patients with PD-pRBD+
Significantly decreased functional connectivity (FC) in the left dorsolateral prefrontal cortex (DLPFC) was detected in the right medial frontopolar area 2 (Fp2) and the bilateral inferior occipital gyri in patients with PD-pRBD+ compared with patients with PD-pRBD− at baseline (Table 2, Figure 4)
Summary
Sleep disturbances are frequently experienced in patients with Parkinson’s disease (PD) (Fereshtehnejad et al, 2017; Jozwiak et al, 2017). Rapid eye movement (REM) sleep behavior disorder (RBD) affects 30–40% of PD (Sixel-Döring et al, 2016), which is associated with early neuropathological progression of this disease (Muzur et al, 2002; Vendette et al, 2007; Kim and Jeon, 2014; Pagano et al, 2018; Kim et al, 2019, 2020; Figorilli et al, 2020). A growing body of evidence have revealed that patients with PD having RBD have significantly impaired executive function (Fantini et al, 2018; Kamble et al, 2019), which significantly worsened during the progression of RBD symptoms in PD (Figorilli et al, 2020). Little is known about whether DLPFC activity demonstrates a specific alteration pattern in patients with PD having RBD compared with those without RBD. The neurobiological mechanisms underlying this dysfunction in early PD and the progressive alterations over time remain largely unexplored
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