Plasma NfL, clinical subtypes and motor progression in Parkinson's disease.

INTRODUCTION: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. METHODS: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. RESULTS: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. CONCLUSION: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments

Subcortical matter in the α-synucleinopathies spectrum: an MRI pilot study.

α-Synucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation from brainstem structures to the neocortex. PD and DLB are clinically distinguishable, while discrimination between Parkinson Disease Dementia (PDD) and DLB can be subtle and based on the temporal relationship between motor and cognitive symptoms. To explore patterns of subcortical atrophy in PD, PDD and DLB, and assess specific differences between PD and PDD, and between DLB and PDD. 16 PD, 11 PDD and 16 DLB patients were recruited and underwent 1.5 Tesla structural MRI scanning. Segmentation of subcortical structures was performed with a well-validated, fully-automated tool, and volume and shape for each structure were compared between groups. PDD and DLB patients showed global subcortical atrophy compared to PD patients. Greater hippocampal atrophy was the specific trait that distinguished PDD from PD, while greater atrophy of the pallidi discriminated DLB from PDD. Vertex analysis revealed specific shape differences in both structures. Our results suggest that automated, time-sparing, subcortical volumetry may provide diagnostically useful information in α-synucleinopathies. Future studies on larger samples and with iron-sensitive MRI contrasts are needed