NPJ Parkinson's Disease最新文献

Creativity is the ability to generate novel and meaningful ideas or behaviors, encompassing both artistic originality and personal satisfaction. Emerging evidence suggests that people with Parkinson’s disease (PD) may experience changes in creativity. This study examines the prevalence of creativity changes in PD using cross-sectional data from the Netherlands (PRIME-NL, 2021–2023). Participants (N = 793) self-reported creativity changes, demographics, clinical factors, and pre-diagnosis creative engagement via a self-structured questionnaire. Descriptive analyses revealed that 41% of respondents reported creativity changes: 12% experienced an increase, 22% a decrease, and 7% fluctuations. Ordinal regression analysis showed that longer disease duration and dopamine agonists were associated with increased creativity, while older age and prior creative engagement predicted decreases. A sub-cohort (n = 292) reported creativity changes across seven domains, with changes most frequently observed in everyday creativity, sports/movement, and fine art/design. These findings underscore the need for further research on creativity in PD to inform person-centered treatment strategies.

Elevated levels of the inflammatory enzyme myeloperoxidase (MPO) in the blood are associated with the development of age-related inflammatory diseases. Given that age, inflammation, and blood MPO play a role in the pathogenesis of Parkinson´s disease (PD), we hypothesized that serum MPO could be associated with PD status. This case-control study (199 participants) was conducted using an extensive protocol, and the concentration and activity of MPO in blood serum were measured. The findings reveal that serum MPO concentration and activity are significantly increased in the patients, and that rates of PD in all individuals are associated with increasing tertiles of MPO concentration and activity. In multivariate logistic regression model adjusting for confounding factors, MPO activity (not concentration) is the factor that is most associated with PD status (OR, 6.921, P = 0.001). Mental depression is directly associated with MPO activity and with PD status (OR, 0.121, B = −2.108, P = 0.002). The use of statins or nonsteroidal anti-inflammatory drugs significantly reduces serum MPO activity, but the possible association with the odds of having PD does not survive correction for multiple testing. In summary, both serum MPO concentration and activity are increased in patients with PD, but only MPO enzyme activity is associated with PD status. These findings may have implications for the evaluation of PD.

Recent studies demonstrate that Parkinson’s disease (PD) is associated with dysregulated metabolic flux through the kynurenine pathway (KP), in which tryptophan is converted to kynurenine (KYN), and KYN is subsequently metabolized to neuroactive compounds quinolinic acid (QA) and kynurenic acid (KA). Here, we used mass-spectrometry to compare blood and cerebral spinal fluid (CSF) KP metabolites between 158 unimpaired older adults and 177 participants with PD. We found increased neuroexcitatory QA/KA ratio in both plasma and CSF of PD participants associated with peripheral and cerebral inflammation and vitamin B₆ deficiency. Furthermore, increased QA tracked with CSF tau, CSF soluble TREM2 (sTREM2) and severity of both motor and non-motor PD clinical symptoms. Finally, PD patient subgroups with distinct KP profiles displayed distinct PD clinical features. These data validate the KP as a site of brain and periphery crosstalk, integrating B-vitamin status, inflammation and metabolism to ultimately influence PD clinical manifestation.

Compound network dynamics in beta and gamma bands determine the severity of bradykinesia in Parkinson’s disease. We explored its subthalamic stimulation related changes parallel with improvement of complex hand movements. Thirty eight patients with Parkinson’s disease treated with bilateral stimulation accomplished voluntary and traced spiral drawing with their more affected hand on a digital tablet. A 64 channel electroencephalography was recorded, low and high beta and gamma power was computed in subthalamic and motor cortical sources at four stimulation levels. Subthalamic cortical effective connectivity was calculated, and subnetwork models were created. Beta power decreased, and gamma power increased in sources ipsilateral to stimulation with increasing stimulation intensity. Networks comprising the primary motor cortex played a dominant role in predicting the improvement of voluntary drawing speed. Subthalamic stimulation diminished the hyperdirect high beta information processing and promoted the cortico cortical interactions of the primary motor cortex in the high gamma band.

Early identification of cognitive decline (CD) in de novo Parkinson’s disease (PD) is crucial for choosing appropriate therapies and recruiting for clinical trials. However, existing prognostic models lack flexibility, scalability and require costly instrumentation. This study explores the utility of standard clinical questionnaires and criteria to predict CD in de novo PD. A total of 186 patients from the Parkinson Progression Markers Initiative (PPMI) and 48 patients from the Biomarkers of Parkinson’s Disease project (BIO-PD) underwent clinical interviews, comprehensive tests, and questionnaires. A model based only on age of disease onset, history of stroke, history of fainting, and vocalization during dreams predicted CD in 2 and 4-year horizons with an area under curve (AUC) of 70% ± 10% standard deviation (cross-validated PPMI), 79% (overall PPMI), and 78% (validation in BIO-PD). This approach enables rapid preliminary screening using just four simple questions, achieving predictive accuracy comparable to instrumentation-based methods while reducing assessment time.

Parkinson’s disease (PD) is associated with chronic sterile inflammation and persistent inflammasome activation involving α-synuclein and ASC protein aggregates, but the underlying mechanisms of the neuroinflammatory response remain unclear. Here, we used midbrain postmortem samples from donors with and without α-synucleinopathies to assess the expression of inflammasome proteins in patients with Parkinsonism. We show that dopaminergic neurons exhibit increased expression of ASC, NOD-like receptor protein (NLRP) 1, and modification of α-synuclein phosphorylation at serine129 (pS129) within the Lewy body inclusions, whereas NLRP3 was identified mainly in microglial. Moreover, treatment of LRRK2 cells with ASC specks from PD and Lewy body dementia patients induced inflammasome activation and cytotoxicity that was blocked by IC100. Administration of preformed α-synuclein aggregates to microglia resulted in a significant elevation in pS129, and this effect was also blocked by IC100. Thus, IC100 may be a promising therapeutic strategy for inflammatory disease modification in synucleinopathies and other diseases.

Parkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder. This study aimed to identify different patterns of early brain degeneration in PD patients and investigate their clinical relevance. 179 early-stage PD patients and 115 healthy controls were included. We assessed cortical morphology, white matter microstructure, and subcortical iron metabolism using multimodal magnetic resonance imaging and employed clustering techniques to identify subtypes. Two subtypes were identified: the early-deterioration subtype, characterized by fronto-temporal atrophy, parietal thickening, widespread reductions in fractional anisotropy (FA) values, and increased subcortical iron content, which exhibited more severe baseline symptoms and a trend of faster memory decline; and the early-compensatory subtype, characterized by rostral middle frontal atrophy, parietal-occipital thickening, increased FA values, and normal iron content, which exhibited milder symptoms initially but experienced faster progression of both motor and non-motor symptoms. These discoveries provided new insights into disease heterogeneity and facilitated the exploration of early neurodegenerative mechanisms.

Unintentional weight loss is common among patients with Parkinson’s disease (PD) and is associated with poor quality of life and accelerated disease progression. To explore how early α-synuclein pathology contributes to metabolic dysregulation leading to weight loss in PD, transgenic mice overexpressing human wild-type α-synuclein (α-Syn) and controls were fed a high-fat diet (HFD) chow for 4 months. Compared with controls on HFD, α-Syn mice on HFD exhibited a dramatically leaner phenotype, improved glucose tolerance, a major decrease in fat mass, an increase in energy expenditure, a decrease in insulin signaling in the olfactory bulb, aggravated olfactory and motor dysfunctions, and an increase in mortality. Our results show that high-fat diet in α-Syn mice provides a sensitive tool for assessing the underlying mechanism of metabolic dysfunction and its impact on weight loss and disease progression in PD. Moreover, a role is proposed for olfactory dysfunction in PD-related unintentional weight loss.

Apathy is a disabling symptom in Parkinson’s disease (PD). The effect of dopaminergic treatment on apathy is inconsistent, depending on the stage of the disease, the type of apathy and strongly influenced by placebo effect. Our study assessed the evolution of a cohort of 86 de novo, drug naive PD patients for 4 years, after dopaminergic treatment introduction. The main objective of the study was the change of apathy from baseline to follow-up and secondary outcomes were the change of other neuropsychiatric symptoms. At 4 years there was an improvement of apathy (p = 0.002), mainly driven by improvement of baseline apathy (p = 0.001). This was associated with an improvement of anxiety (p = 0.001), an increase in hyperdopaminergic behavior including nocturnal hyperactivity with consecutive diurnal sleepiness (p = 0.001 and p < 0.001), independently of the presence of apathy at baseline. These findings confirm, in a large real-life cohort, that dopaminergic treatment improves motivational apathy in early PD.

Idiopathic REM sleep behaviour disorder (iRBD) is considered a prodromal form of Parkinson’s Disease (PD), potentially exhibiting similar patterns of neurodegeneration, such as brain iron changes. We investigated midbrain and pallidal iron using quantitative susceptibility mapping (QSM) in 16 iRBD patients, 30 PD patients, and 38 age-matched healthy controls (HCs) with 3T MRI. QSM revealed elevated substantia nigra pars compacta (SNc) mean susceptibility in both iRBD and PD patient groups compared to HCs, though iRBD and PD QSM measures did not differ. There were no SN pars reticulata group differences. Mean susceptibility was reduced for PD relative to iRBD and HCs in the globus pallidus externa (GPe). Furthermore, mean susceptibility was reduced for PD relative to iRBD in the GP interna (GPi). GPe/GPi mean susceptibility decreased with PD subgroup motor severity. Consistent with this, QSM in left GPi and MDS-UPDRS-III scores correlated negatively in PD patients, as well as in iRBD and PD patients combined. PD patients also evidenced higher mean susceptibility in the right ventral tegmental area (VTA) compared to iRBD and HCs, consistent with later VTA degeneration. RBD symptomatology did not correlate with QSM values. Combining SNc, GPe, GPi, and VTA QSM values, we distinguished iRBD-HCs, PD-HCs, and iRBD-PD patients at single-subject levels (0.84, 0.86, and 0.81 accuracies), using ROC curve analyses with repeated k-folds cross-validation. Using 3T MRI, QSM values in SNc, GPe, GPi, and VTA demonstrate promise as investigational measures and diagnostic/progression biomarkers of prodromal and early PD.