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Sphingolipid dysregulation in Parkinson's disease (PD) may affect the release and uptake of striatal dopamine. However, the longitudinal relationship between sphingolipids, striatal dopaminergic degeneration, and clinical correlates in idiopathic PD (iPD) remain unclear. To investigate the relationship between plasma sphingolipids, striatal dopamine transporter specific binding ratio (DAT-SBR) and clinical symptoms in iPD. We included 283 iPD patients and 121 healthy controls (HC) from the Parkinson's Progression Markers Initiative (PPMI), utilizing available data on plasma sphingolipids (sphingomyelin [SM] and ceramide [CER]), striatal DAT-SBR and clinical assessments. Linear mixed models and mediation analyses were used to examine the relationship between sphingolipids, DAT-SBR, and clinical progression in iPD. Lower baseline SM levels were significantly associated with a faster decline in DAT-SBR in both the caudate (p = 0.015) and putamen (p = 0.002), with the putamen association remaining significant after Bonferroni correction (p = 0.015). No significant association was found for CER. Patients in the lowest quartile of baseline SM showed faster progression in MDS-UPDRS I (p = 0.013) and II (p = 0.011), while those in the lowest quartile of baseline CER showed faster progression in MDS-UPDRS II (p = 0.013) and III (p = 0.033). The progression rate of caudate DAT-SBR partially mediated the relationships between SM and progression in MDS-UPDRS I and II (p < 0.01). Sphingolipids are associated with worse dopaminergic degeneration and potentially linked to faster progression in iPD, holding the promise for identifying individuals with faster progression in iPD. • Lower SM levels are linked to faster striatal DAT-SBR decline in idiopathic PD. • CER and SM are potentially associated with progression in MDS-UPDRS scores in idiopathic PD. • Caudate DAT-SBR progression partially mediates SM effects. • Plasma SM can help identify rapid progressors in idiopathic PD. [ABSTRACT FROM AUTHOR]

To investigate interocular asymmetry (IA) of retinal structure and vessel density in patients with Parkinson's disease (PD) and normal controls (NC). Seventy-eight subjects including 40 PD patients and 38 NC had completed optical coherence tomography angiography (OCTA) and neurological examinations for three rating scales (UPDRS-III, MMSE and MoCA). The IA was calculated by the absolute value of difference in right and left eyes. The IA of thickness in macular ganglion cell inner-plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP), radial peripapillary capillary (RPC) were obtained from OCTA. The motor-symptom-onset side of eyes showed lower vessel density in parafovea of SCP (51.09 ± 3.46 vs 49.81 ± 4.16, P = 0.03) and superior hemi of perifovea DCP (49.55 ± 5.81 vs 47.33 ± 5.71, = 0.04). The PD patients showed larger IA in thickness of superior half of pRNFL (5.27 [2.67, 10.87] vs 3.08 [1.62, 5.61], P = 0.02) and parafovea GCIPL (2.40[1.25, 6.35] vs 1.40[0.50, 2.45], P = 0.02). No significant interocular asymmetry was found in vessel density between PD and NC. A higher UPDRS-III scale was associated with larger IA in GCIPL (β = 0.093, P = 0.001) and smaller IA in DCP (β = −0.065, P = 0.037). The motor-symptom-onset side of eyes showed more severe loss of macular vessel density than the other side of eyes. The PD patients showed asymmetrical structural change in GCIPL and pRNFL, which showed the potential as the diagnostic biomarker for PD. • Our study discovers the interocular asymmetry of retinal structure in patients with Parkinson's disease. • Our study discovers the relationship between severity of Parkinson's disease and asymmetry of retinal vasculature. • Our study is the first to demonstrate the asymmetric propagation of microvascular change in patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is associated with structural alterations of the retina. However, it remains unknown whether these changes are present in PD with mild cognitive impairment (MCI). The purpose of the study was to evaluate the retinal microvasculature using optical coherence tomography angiography (OCTA) to assess possible retinal microvascular impairments associated with PD and PD with MCI.Methods: This study included 83 eyes of 45 PD patients and 83 eyes of 42 healthy controls. All subjects underwent complete neurological and ophthalmological examinations before measurements. Cognitive function was also measured in PD patients. Retinal microvasculature was evaluated with OCTA. Vessel density in the superficial capillary plexus (SRCP), deep capillary plexus (DRCP), and radial peripapillary capillaries (RPC) and intraretinal layer thickness in the peripapillary retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) were analysed. Correlations between vessel density and cognitive function were analysed in the PD group.Results: Parafoveal vessel density in the SRCP and DRCP were lower in the eyes of PD patients than healthy controls (P < 0.05). However, there were no significant differences in the RPC (P = 0.120), RNFL (P = 0.303) or GCC (P = 0.375) between PD patients and healthy controls. Lower executive function scores were associated with lower vessel density in the DRCP of PD patients (P < 0.05, 95% CI [0.133,1.342]).Conclusion: OCTA revealed lower macular microvascular density in PD patients and microvascular impairments in the deep retinal capillary layer in PD patients with executive dysfunction. These parameters might have potential utility as early disease diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aβ 1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aβ 1-42 /αsyn ratio. CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins. • This study aimed to investigate the relationship of CP volume and PD cognitive progression. • Larger CP volume may suggest a rapid deterioration of memory in early PD. • CSF biomarker ratio of Aβ 1-42 /αsyn may partly mediate pathological effect of CP volume. [ABSTRACT FROM AUTHOR]