Search Results (412)

Freezing of gait (FoG) impairs mobility and daily functioning and increases the risk of falls, leading to a reduced quality of life (QoL) in people with Parkinson’s disease (PD). The Cue2walk, a wearable smart cueing device, can detect FoG and hereupon provides rhythmic cues to help people with PD manage FoG in daily life. This study investigated the user experiences and device usage of the Cue2walk, and its impact on health-related QoL, FoG and daily activities. Twenty-five users of the Cue2walk were invited to fill out an online survey, which included a modified version of the EQ-5D-5L, tailored to the use of the Cue2walk, and its scale for health-related QoL, three FoG-related questions, and a question about customer satisfaction. Sixteen users of the Cue2walk completed the survey. Average device usage per day was 9 h (SD 4). Health-related QoL significantly increased from 5.2/10 (SD 1.3) to 6.2/10 (SD 1.3) (p = 0.005), with a large effect size (Cohen’s d = 0.83). A total of 13/16 respondents reported a positive effect on FoG duration, 12/16 on falls, and 10/16 on daily activities and self-confidence. Customer satisfaction was 7.8/10 (SD 1.7). This pilot study showed that Cue2walk usage per day is high and that 15/16 respondents experienced a variety of positive effects since using the device. To validate these findings, future studies should include a larger sample size and a more extensive set of questionnaires and physical measurements monitored over time. Full article

Neurodegenerative diseases (NDDs) such as Alzheimer’s, Parkinson’s, ALS, and Huntington’s pose a growing global challenge due to their complex pathobiology and aging demographics. Once considered as cellular debris, small extracellular vesicles (sEVs) are now recognized as active mediators of intercellular signaling in NDD progression. These nanovesicles (~30–150 nm), capable of crossing the blood–brain barrier, carry pathological proteins, RNAs, and lipids, facilitating the spread of toxic species like Aβ, tau, TDP-43, and α-synuclein. sEVs are increasingly recognized as valuable diagnostic tools, outperforming traditional CSF biomarkers in early detection and disease monitoring. On the therapeutic front, engineered sEVs offer a promising platform for CNS-targeted delivery of siRNAs, CRISPR tools, and neuroprotective agents, demonstrating efficacy in preclinical models. However, translational hurdles persist, including standardization, scalability, and regulatory alignment. Promising solutions are emerging, such as CRISPR-based barcoding, which enables high-resolution tracking of vesicle biodistribution; AI-guided analytics to enhance quality control; and coordinated regulatory efforts by the FDA, EMA, and ISEV aimed at unifying identity and purity criteria under forthcoming Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. This review critically examines the mechanistic roles, diagnostic potential, and therapeutic applications of sEVs in NDDs, and outlines key strategies for clinical translation. Full article

On a worldwide scale, neurodegenerative diseases, including multiple sclerosis, Parkinson’s, and Alzheimer’s, face considerable healthcare challenges demanding the development of novel approaches to early detection and efficient treatment. With its ability to provide real-time patient monitoring, customized medical care, and advanced predictive analytics, artificial intelligence (AI) is fundamentally transforming the way healthcare is provided. Through the integration of wearable physiological sensors, motion sensors, and neurological assessment tools, the NeuroPredict platform harnesses AI and smart sensor technologies to enhance the management of specific neurodegenerative diseases. Machine learning algorithms process these data flows to find patterns that point out disease evolution. This paper covers the design and architecture of the NeuroPredict platform, stressing the ethical and regulatory requirements that guide its development. Initial development of AI algorithms for disease monitoring, technical achievements, and constant enhancements driven by early user feedback are addressed in the discussion section. To ascertain the platform’s trustworthiness and data security, it also points towards risk analysis and mitigation approaches. The NeuroPredict platform’s capability for achieving AI-driven smart healthcare solutions is highlighted, even though it is currently in the development stage. Subsequent research is expected to focus on boosting data integration, expanding AI models, and providing regulatory compliance for clinical application. The current results are based on incremental laboratory tests using simulated user roles, with no clinical patient data involved so far. This study reports an experimental technology evaluation of modular components of the NeuroPredict platform, integrating multimodal sensors and machine learning pipelines in a laboratory-based setting, with future co-design and clinical validation foreseen for a later project phase. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that impairs motor function, including the fine motor control required for handwriting. Traditional diagnostic methods often lack sensitivity and objectivity in the early stages, limiting opportunities for timely intervention. There is a growing need for non-invasive, accessible tools capable of capturing subtle motor changes that precede overt clinical symptoms. Among early PD manifestations, handwriting impairments such as micrographia have shown potential as digital biomarkers. However, conventional handwriting analysis remains subjective and limited in scope. Recent advances in artificial intelligence (AI) and machine learning (ML) enable automated analysis of handwriting dynamics, such as pressure, velocity, and fluency, collected via digital tablets and smartpens. These tools support the detection of early-stage PD, monitoring of disease progression, and assessment of therapeutic response. This paper highlights how AI-enhanced handwriting analysis provides a scalable, non-invasive method to support diagnosis, enable remote symptom tracking, and personalize treatment strategies in PD. This approach integrates clinical neurology with computer science and rehabilitation, offering practical applications in telemedicine, digital health, and personalized medicine. By capturing dynamic features often missed by traditional assessments, AI-based handwriting analysis contributes to a paradigm shift in the early detection and long-term management of PD, with broad relevance across neurology, digital diagnostics, and public health innovation. Full article

Background: People with Parkinson’s disease (PwPD) often experience sleep disturbances and reduced physical activity. Altered sleep behavior and lower daily steps have been linked to disease severity and symptom burden. Although physical activity may influence sleep, few studies have examined the relationship between sleep parameters and daily steps in PD. This scoping review aimed to review current knowledge on sleep parameters and daily steps collected concurrently in PwPD and their potential association. Methods: A systematic search was conducted in five databases, PubMed, Web of Science, Sport Discus, Cochrane Library, and Scopus. Methodological quality was assessed using a customized quality checklist developed by Zanardi and collaborators for observational studies, based on Downs and Black’s work. Results: Out of 1421 records, five studies met the eligibility criteria and were included in the review. Four studies reported wearable-based measurements of both step count and sleep parameters, while one study reported wearable-based measurements of step count and self-reported sleep measures. Two studies examined the association between sleep parameters and step count. One study did not find any correlation between sleep and step count, whereas one study reported a positive correlation between daytime sleepiness and step count. Conclusions: This review highlighted the lack of research investigating the relationship between sleep parameters and step count as an indicator of physical activity in PwPD. Findings are inconsistent with a potential positive correlation emerging between daytime sleepiness and step count. Findings also pointed toward lower step count and reduced sleep duration in PwPD, as measured with wearable devices. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder commonly marked by upper limb tremors that interfere with daily activities. Wearable devices, such as smartwatches, represent a promising solution for continuous and objective monitoring in PD. This study aimed to develop and validate a tremor-detection algorithm using smartwatch sensors. Data were collected from 21 individuals with PD and 27 healthy controls using both a commercial inertial measurement unit (G-Sensor, BTS Bioengineering, Italy) and a smartwatch (Apple Watch Series 3). Participants performed standardized arm movements while sensor signals were synchronized and processed to extract relevant features. Statistical analyses assessed discriminant and concurrent validity, reliability, and accuracy. The algorithm demonstrated moderate to strong correlations between smartwatch and commercial IMU data, effectively distinguishing individuals with PD from healthy controls showing associations with clinical measures, such as the MDS-UPDRS III. Reliability analysis demonstrated agreement between repeated measurements, although a proportional bias was noted. Power spectral density (PSD) analysis of accelerometer and gyroscope data along the x-axis successfully detected the presence of tremors. These findings support the use of smartwatches as a tool for detecting tremors in PD. However, further studies involving larger and more clinically impaired samples are needed to confirm the robustness and generalizability of these results. Full article

Diagnosing Parkinson’s disease (PD) through speech analysis is a promising area of research, as speech impairments are often one of the early signs of the disease. This study investigates the efficacy of fine-tuning pre-trained Automatic Speech Recognition (ASR) models, specifically Wav2Vec 2.0 and HuBERT, for PD detection using transfer learning. These models, pre-trained on large unlabeled datasets, can be capable of learning rich speech representations that capture acoustic markers of PD. The study also proposes the integration of a supervised contrastive (SupCon) learning approach to enhance the models’ ability to distinguish PD-specific features. Additionally, the proposed ASR-based features were compared against two common acoustic feature sets: mel-frequency cepstral coefficients (MFCCs) and the extended Geneva minimalistic acoustic parameter set (eGeMAPS) as a baseline. We also employed a gradient-based method, Grad-CAM, to visualize important speech regions contributing to the models’ predictions. The experiments, conducted using the NeuroVoz dataset, demonstrated that features extracted from the pre-trained ASR models exhibited superior performance compared to the baseline features. The results also reveal that the method integrating SupCon consistently outperforms traditional cross-entropy (CE)-based models. Wav2Vec 2.0 and HuBERT with SupCon achieved the highest F1 scores of 90.0% and 88.99%, respectively. Additionally, their AUC scores in the ROC analysis surpassed those of the CE models, which had comparatively lower AUCs, ranging from 0.84 to 0.89. These results highlight the potential of ASR-based models as scalable, non-invasive tools for diagnosing and monitoring PD, offering a promising avenue for the early detection and management of this debilitating condition. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder leading to movement impairment, cognitive decline, and psychiatric symptoms. Key manifestations of PD include bradykinesia (the slowness of movement), changes in voice or speech, and gait disturbances. The quantification of neurological disorders through voice analysis has emerged as a rapidly expanding research domain, offering the potential for non-invasive and large-scale monitoring. This review explores existing research on the application of machine learning (ML) in speech, voice, and language processing for the diagnosis of PD. It comprehensively analyzes current methodologies, highlights key findings and their associated limitations, and proposes strategies to address existing challenges. A systematic review was conducted following PRISMA guidelines. We searched four databases: PubMed, Web of Science, Scopus, and IEEE Xplore. The primary focus was on the diagnosis, detection, or identification of PD through voice, speech, and language characteristics. We included 34 studies that used ML techniques to detect or classify PD based on vocal features. The most used approaches involved free speech and reading-speech tasks. In addition to widely used feature extraction toolkits, several studies implemented custom-built feature sets. Although nearly all studies reported high classification performance, significant limitations were identified, including challenges in comparability and incomplete integration with clinical applications. Emerging trends in this field include the collection of real-world, everyday speech data to facilitate longitudinal tracking and capture participants’ natural behaviors. Another promising direction involves the incorporation of additional modalities alongside voice analysis, which may enhance both analytical performance and clinical applicability. Further research is required to determine optimal methodologies for leveraging speech and voice changes as early biomarkers of PD, thereby enhancing early detection and informing clinical intervention strategies. Full article

This study presents a hybrid ensemble learning framework for the joint detection and motor severity prediction of Parkinson’s disease (PD) using biomedical voice features. The proposed architecture integrates a deep multimodal fusion model with dense expert pathways, multi-head self-attention, and multitask output branches to simultaneously perform binary classification and regression. To ensure data quality and improve model generalization, preprocessing steps included outlier removal via Isolation Forest, two-stage feature scaling (RobustScaler followed by MinMaxScaler), and augmentation through polynomial and interaction terms. Borderline-SMOTE was employed to address class imbalance in the classification task. To enhance prediction performance, ensemble learning strategies were applied by stacking outputs from the fusion model with tree-based regressors (Random Forest, Gradient Boosting, and XGBoost), using diverse meta-learners including XGBoost, Ridge Regression, and a deep neural network. Among these, the Stacking Ensemble with XGBoost (SE-XGB) achieved the best results, with an R² of 99.78% and RMSE of 0.3802 for UPDRS regression and 99.37% accuracy for PD classification. Comparative analysis with recent literature highlights the superior performance of our framework, particularly in regression settings. These findings demonstrate the effectiveness of combining advanced feature engineering, deep learning, and ensemble meta-modeling for building accurate and generalizable models in voice-based PD monitoring. This work provides a scalable foundation for future clinical decision support systems. Full article

Phages are considered effective biocontrol agents for improving food safety due to their specific interaction with pathogens. It is essential to recognise that zero risk does not exist, and as biological agents, phages must be continuously evaluated for potential adverse effects on human health in both food and clinical contexts. This is the first bacteriophage risk profile performed according to the methodology recommended by FAO/WHO and EFSA. Key safety concerns regarding phage use in the food sector include the risk of horizontal gene transfer, especially regarding antibiotic resistance genes among bacteria. While such occurrences are contextually dependent and rare, they warrant further scrutiny. Moreover, improper phage application during food processing could lead to the emergence of resistant bacterial strains, compromising the long-term efficacy of phage interventions. Currently, there is limited evidence indicating any health risks linked to phage consumption or pathogenic behaviour (e.g., possible association between bacteriophages and Parkinson’s disease). Despite numerous studies affirming the safety and efficacy of phages in the food chain, continuous monitoring remains crucial. In particular, the responses of susceptible populations to phage exposure should be carefully examined. Full article

Heterozygous mutations in the GBA1 gene, encoding the enzyme glucocerebrosidase (GCase), are major risk factors for Parkinson’s Disease (PD). Ambroxol, a small chaperone originally used as a mucolytic agent, has been shown to cross the blood–brain barrier, enhance GCase activity, and reduce α-synuclein levels, making it a promising therapeutic candidate for disease-modifying effects in GBA1-associated PD (GBA1-PD). This study aimed to develop a method to quantify ambroxol levels in human plasma and cerebrospinal fluid (CSF) using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Ambroxol was determined by online solid-phase extraction (SPE), coupled with LC-MS/MS, by gradient elution on a monolithic column. Detection employed a 3200 QTRAP tandem mass spectrometer in the positive electrospray ionization mode. Calibration curves exhibited linearity across the analyzed ranges in both plasma and CSF. The recovery rate ranged from 106.7% to 113.5% in plasma and from 99.0% to 103.0% in CSF. No significant matrix effect was observed. Intra-day and inter-day precisions were below 11.8% in both matrices, and accuracy ranged from 89.9% to 103.1% in plasma and from 96.3% to 107.8% in CSF. We evaluated and confirmed the stability of the analyte in plasma and CSF across various storage conditions. The method was successfully validated according to European Medicine Agency (EMA) guidelines and its applicability was confirmed in the context of a multicenter, randomized, double-blind, placebo-controlled, phase II study, designed to monitor the ambroxol levels in the plasma and CSF of GBA1-PD. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. The accurate and continuous monitoring of these symptoms is essential for optimizing treatment strategies and improving patient outcomes. Traditionally, clinical assessments have relied on scales and methods that often lack the ability for continuous, real-time monitoring and can be subject to interpretation bias. Recent advancements in wearable technologies, such as smartphones, smartwatches, and activity trackers (ATs), present a promising alternative for more consistent and objective monitoring. This review aims to evaluate the use of smartphones and smart wrist devices, like smartwatches and activity trackers, in the management of PD, assessing their effectiveness in symptom evaluation and monitoring and physical performance improvement. Studies were identified by searching in PubMed, Scopus, Web of Science, and Cochrane Library. Only 13 studies of 1027 were included in our review. Smartphones, smartwatches, and activity trackers showed a growing potential in the assessment, monitoring, and improvement of motor symptoms in people with PD, compared to clinical scales and research-grade sensors. Their relatively low cost, accessibility, and usability support their integration into real-world clinical practice and exhibit validity to support PD management. Full article

In addition to axial motor complications such as abnormal posture, instability, falls, and gait variability, neurodegenerative diseases like Parkinsonian syndromes include executive dysfunction, Parkinson’s disease dementia, and neuropsychiatric symptoms. These motor disorders significantly affect mobility, quality of life, and well-being. Recently, physical activity of various intensities monitored both remotely and face-to-face via digital health technologies, mobile platforms, or sensory cues has gained relevance in managing idiopathic and atypical Parkinson’s disease (PD and APD). Remote monitoring solutions, including home-based digital health assessments using semi-structured activities, offer unique advantages. Real-world gait parameters like walking speed can now be continuously assessed with body-worn sensors. Developing effective strategies to slow pathological aging and mitigate neurodegenerative progression is essential. This study presents outcomes of using digital health technologies (DHTs) for remote assessment of motor function, physical activity, and daily living tasks, aiming to reduce disease progression in PD and APD. In addition to wearable inertial sensors, clinical rating scales and digital biomarkers enhance the ability to characterize and monitor motor symptoms. By reviewing recent literature, we identified emerging trends in quantifying and intervening in neurodegeneration using tools that evaluate both remote and face-to-face physical activity. Our findings confirm that DHTs offer accurate detection of motor fluctuations and support clinical evaluations. In conclusion, DHTs represent a scalable, effective strategy for improving the clinical management of PD and APD. Their integration into healthcare systems may enhance patient outcomes, support early intervention, and help delay the progression of both motor and cognitive symptoms in aging individuals. Full article

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder with a prolonged prodromal phase and progressive symptom burden. Traditional monitoring relies on clinical visits post-diagnosis, limiting the ability to capture early symptoms and real-world disease progression outside structured assessments. Social media provides an alternative source of longitudinal, patient-driven data, offering an opportunity to analyze both pre-diagnostic experiences and later disease manifestations. This study evaluates the feasibility of using Facebook to analyze PD-related discourse and disease timelines. Methods: Participants (N = 60) diagnosed with PD, essential tremor, or atypical parkinsonism, along with caregivers, were recruited. Demographic and clinical data were collected during structured interviews. Participants with Facebook accounts shared their account data. PD-related posts were identified using a Naïve Bayes classifier (recall: 0.86, 95% CI: 0.84–0.88, AUC = 0.94) trained on a ground-truth dataset of 6750 manually labeled posts. Results: Among participants with PD (PwPD), Facebook users were significantly younger but had similar Movement Disorder Society-United Parkinson’s Disease Rating Scale scores and disease duration compared to non-users. Among Facebook users with PD, 90% had accounts before diagnosis, enabling retrospective analysis of pre-diagnostic content. PwPD maintained 14 ± 3 years of Facebook history, including 5 ± 6 years pre-diagnosis. On average, 3.6% of all posts shared by PwPD were PD-related, and 1.7% of all posts shared before diagnosis were PD-related. Overall, 69% explicitly referenced PD, and 93% posted about PD-related themes. Conclusions: Facebook is a viable platform for studying PD progression, capturing both early content from the premorbid period and later-stage symptoms. These findings support its potential for disease monitoring at scale. Full article

Parkinson’s disease and related synucleinopathies, including dementia with Lewy bodies and multiple system atrophy, are characterised by the pathological aggregation of the α-synuclein (aSyn) protein in neuronal and glial cells, leading to cellular dysfunction and neurodegeneration. This review synthesizes knowledge of aSyn biology, including its structure, aggregation mechanisms, cellular interactions, and systemic influences. We highlight the structural diversity of aSyn aggregates, ranging from oligomers to fibrils, their strain-like properties, and their prion-like propagation. While the role of prion-like mechanisms in disease progression remains a topic of ongoing debate, these processes may contribute to the clinical heterogeneity of synucleinopathies. Dysregulation of protein clearance pathways, including chaperone-mediated autophagy and the ubiquitin–proteasome system, exacerbates aSyn accumulation, while post-translational modifications influence its toxicity and aggregation propensity. Emerging evidence suggests that immune responses and alterations in the gut microbiome are key modulators of aSyn pathology, linking peripheral processes—particularly those of intestinal origin—to central neurodegeneration. Advances in biomarker development, such as cerebrospinal fluid assays, post-translationally modified aSyn, and real-time quaking-induced conversion technology, hold promise for early diagnosis and disease monitoring. Furthermore, positron emission tomography imaging and conformation-specific antibodies offer innovative tools for visualising and targeting aSyn pathology in vivo. Despite significant progress, challenges remain in accurately modelling human synucleinopathies, as existing animal and cellular models capture only specific aspects of the disease. This review underscores the need for more reliable aSyn biomarkers to facilitate the development of effective treatments. Achieving this goal requires an interdisciplinary approach integrating genetic, epigenetic, and environmental insights. Full article