Movement Disorders最新文献

Background: Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing the number of mitochondrial DNA copies within a cell, serves as an easily assessable proxy for mitochondrial function.

Objective: This study aimed to assess the diagnostic and prognostic capabilities of mtDNA-CN in PD.

Methods: We assessed mtDNA-CN in blood samples using whole genome sequencing from 405 patients with PD and 200 healthy controls (HC). We examined the relationship between mtDNA-CN levels and motor symptom severity in PD, as well as their association with dementia development in patients with early-PD (within 3 years of diagnosis).

Results: mtDNA-CN levels were significantly lower in patients with PD compared with HC (P = 1.1 × 10^-5). A negative correlation was discovered between mtDNA-CN level and motor severity in PD (correlation coefficient = -0.20; P = 0.008). Among 210 patients with early-PD, Cox regression analysis demonstrated an association between lower mtDNA-CN levels and a higher risk of developing dementia (hazard ratio [HR] = 0.41, 95% confidence interval: 0.20-0.86, P = 0.02), even after adjusting for age and blood cell count (HR = 0.41, 95% confidence interval: 0.18-0.92, P = 0.03). However, mtDNA-CN levels did not significantly correlate with motor progression in PD.

Conclusion: Our findings suggest that blood mtDNA-CN may function as a diagnostic biomarker for PD and a prognostic marker for dementia in patients with PD. © 2025 International Parkinson and Movement Disorder Society.

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust HC subgroup without cognitive decline, (2) generate regression-based z scores for six cognitive measures using this subgroup, and (3) create a CSS by averaging all z scores.

Results: PD participants scored worse than HCs on all cognitive tests, with larger effects when compared with the robust HC subgroup rather than all HCs. Applying internally derived norms, the largest effects were for processing speed/working memory (Cohen's d = -0.55) and verbal episodic memory (Cohen's d = -0.48 and -0.52). Robust norming shifted PD performance from average (CSS z score = -0.01) to low average (CSS z score = -0.40), with a larger effect for the CSS (PD vs. robust HC subgroup; Cohen's d = -0.60) compared with individual tests.

Conclusions: Patients with PD perform worse cognitively than HCs, particularly in processing speed and verbal memory. Robust norming increases effect sizes and decreases PD scores to expected levels. The CSS outperformed individual tests and may detect cognitive changes in early PD, making it a useful outcome measure in clinical research. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Bilateral lesions of the basal ganglia using termocoagulation or radiation for improving tremor, bradykinesia, and rigidity in people with Parkinson's disease (PD) have been performed starting several decades ago, especially when levodopa and deep brain stimulation (DBS) surgery were not available. However, because of unclear additional benefit compared to unilateral lesion, and particularly to the evidence of increased adverse events occurrence, bilateral lesions were basically abandoned at the end of the 20th century. Therefore, bilateral DBS has become the standard procedure to treat PD. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is an emerging incisionless technique used to produce therapeutic brain ablation. The positive experiences of unilateral MRgFUS ablation for PD, along with the preliminary favorable outcomes of bilateral thalamic MRgFUS for essential tremor, raise the possibility to eventually reintroduce bilateral lesioning in the management of PD motor features. This possibility has so far only been tested in a few small studies. This article reviews the evidence of bilateral lesioning of the basal ganglia to treat PD, and elaborates on current gaps, controversies, and perspectives of the different available neurosurgical procedures and specifically of MRgFUS ablation. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: α-Synuclein (SNCA) gene hypomethylation was reported in idiopathic Parkinson's disease (iPD). Based on a high clinical resemblance between iPD and leucine-rich repeat kinase 2 (LRRK2)-driven Parkinson's disease (L2PD), we investigated the epigenetic status of SNCA in an extensive LRRK2 clinical cohort from Spain.

Methods: We assessed the methylation levels of 23 CpG sites in the SNCA promoter region using peripheral blood DNA from L2PD patients (n = 151), LRRK2 nonmanifesting carriers (n = 55), iPD patients (n = 115), and healthy control subjects (n = 154) (total: N = 475).

Results: Compared with control subjects, we found significant SNCA hypomethylation in 11 of 23 CpGs in L2PD (48%), whereas 22 CpGs (96%) were hypomethylated in iPD. In line with a healthy status, asymptomatic mutation carriers had similar SNCA methylation profiles to control subjects.

Conclusions: This study shows for the first time that SNCA hypomethylation occurs in patients with L2PD. Further studies addressing SNCA methylation status in additional worldwide LRRK2 cohorts are warranted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.