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NPJ Parkinson's Disease Jun 2024The Movement Disorder Society developed research criteria for the detection of the prodromal phase of Parkinson's disease (PD). Accurate identification of this phase is...
The Movement Disorder Society developed research criteria for the detection of the prodromal phase of Parkinson's disease (PD). Accurate identification of this phase is essential for early interventions. Therefore, we investigated the diagnostic value of these research criteria in the general population. Lifelines is an ongoing cohort study of 167,000 participants from the general population of the Northern Netherlands. 160 participants self-reported to have developed PD during three rounds of follow-up of five years each. Data were available to infer six out of eleven risk markers, and six out of twelve prodromal markers. We retrospectively compared the criteria in the prodromal stage of a group of 160 'converters' with 320 age- and sex-matched controls. The overall incidence rate of PD was 0.20 per 1.000 person-years (95% CI: 0.049-0.36), increasing with age and rates were higher in men. The median probability for prodromal PD in PD-converters was 1.29% (interquartile range: 0.46-2.9), compared to 0.83% (0.39-1.8) for controls (P = 0.014). The MDS set of criteria for prodromal PD had an ROC-AUC of 0.577, and was therefore not sufficient to adequately predict conversion to PD. We were unable to predict conversion to PD in the general population using a selection of the prodromal PD research criteria. Ancillary investigations are required to improve the diagnostic accuracy of the criteria, but most are precluded from large-scale use. Strategies, including olfactory tests or alpha-synuclein seeding amplification assays may improve the detection of prodromal PD in the general population.
PubMed: 38926405
DOI: 10.1038/s41531-024-00739-6 -
Health Expectations : An International... Jun 2024Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these...
BACKGROUND
Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these remain poorly understood with suboptimal clinical management. These unmet needs are an important determinant of health-related quality of life (QoL) in PD.
OBJECTIVE
The aim of this study was to gain insights into the experience of living with the NMS of PD in real-time using participatory action methodology.
METHOD
Using the photovoice method, 14 people with PD took photographs to document their experiences of living with the NMS of PD. They composed corresponding written narratives to capture the impact of NMS on their daily activities and QoL. In total, 152 photographs and corresponding narratives were analysed using thematic analysis with an inductive approach.
RESULTS
Four interrelated themes were identified. Emotional well-being and sense of self encompassed a process of adjustment to living with PD. Engaging in valued activities, adopting a positive mindset and utilising coping strategies were thought to enhance confidence and self-esteem. Social support and societal awareness highlighted the importance of supportive relationships and socialising to aid participation and avoid isolation. Barriers to social engagement included the unpredictability of NMS and nonvisible NMS being neglected or misunderstood.
CONCLUSION
Findings demonstrated the far-reaching impact of nonmotor aspects of PD on emotional, occupational and social dimensions. These needs could be addressed through person-centred and comprehensive approaches to care.
PATIENT OR PUBLIC CONTRIBUTION
This study utilised a participatory research approach allowing participants to choose the subjects that mattered to them and how to present their results. Additionally, a group workshop was held with people with PD, their family members and healthcare professionals to guide theme development.
Topics: Humans; Parkinson Disease; Female; Male; Quality of Life; Aged; Middle Aged; Photography; Adaptation, Psychological; Social Support; Activities of Daily Living; Self Concept; Aged, 80 and over; Qualitative Research
PubMed: 38924637
DOI: 10.1111/hex.14124 -
Science Advances Jun 2024Mutations in cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is...
Mutations in cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, . We show that >50% of short RNA-sequencing reads mapping to also map to . Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both and . We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both and . These included protein-coding transcripts from both genes that were translated in human brain, but without the known lysosomal function-yet accounting for almost a third of transcription. Analyzing brain-specific cell types using long-read and single-nucleus RNA sequencing revealed region-specific variations in transcript expression. Overall, these findings suggest nonlysosomal roles for and with implications for our understanding of the role of in health and disease.
Topics: Humans; Glucosylceramidase; Pseudogenes; Brain; Molecular Sequence Annotation; Parkinson Disease; Gaucher Disease; Sequence Analysis, RNA
PubMed: 38924406
DOI: 10.1126/sciadv.adk1296 -
Annals of Clinical and Translational... Jun 2024Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in...
OBJECTIVE
Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in diagnosing various movement disorders, such as Parkinson's disease and dystonia, by detecting disease-specific abnormalities, the specific characteristics of the TCS in cerebellar ataxia remain inconclusive. We aimed to assess the potential value of TCS in patients with cerebellar ataxias for disease diagnosis and severity assessment.
METHODS
TCS on patients with genetic and acquired cerebellar ataxia, including 94 with spinocerebellar ataxias (SCAs) containing 10 asymptomatic carriers, 95 with cerebellar subtype of multiple system atrophy (MSA-C), and 100 healthy controls (HC), was conducted. Assessments included third ventricle width, substantia nigra (SN) and lentiform nucleus (LN) echogenicity, along with comprehensive clinical evaluations and genetic testing.
RESULTS
The study revealed significant TCS abnormalities in patients with cerebellar ataxia, such as enlarged third ventricle widths and elevated rates of hyperechogenic SN and LN. TCS showed high accuracy in distinguishing patients with SCA or MSA-C from HC, with an AUC of 0.870 and 0.931, respectively. TCS abnormalities aided in identifying asymptomatic SCA carriers, effectively differentiating them from HC, with an AUC of 0.725. Furthermore, third ventricle width was significantly correlated with SARA and ICARS scores in patients with SCA3 and SCOPA-AUT scores in patients with MSA-C. The SN area and SARA or ICARS scores in patients with SCA3 were also positively correlated.
INTERPRETATION
Our findings illustrate remarkable TCS abnormalities in patients with cerebellar ataxia, serving as potential biomarkers for clinical diagnosis and progression assessment.
PubMed: 38924300
DOI: 10.1002/acn3.52131 -
Aging Cell Jun 2024Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a...
Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to predict the chronological age of individuals with a 0.79 Pearson correlation and mean estimated error (MAE) of 4.30 years in our validation cohort. Additionally, we analyzed proteins highly weighted by the algorithm to gain insights into changes in CSF and uncover novel insights into brain aging. We also demonstrate a novel method to create a minimal protein clock that uses just 109 protein features from the original clock to achieve a similar accuracy (0.75 correlation, MAE 5.41). Finally, we demonstrate that our clock identifies novel proteins that are highly predictive of age in interactions with other proteins, but do not directly correlate with chronological age themselves. In conclusion, we propose that our CSF protein aging clock can identify novel proteins that influence the rate of aging of the central nervous system (CNS), in a manner that would not be identifiable by examining their individual relationships with age.
PubMed: 38923730
DOI: 10.1111/acel.14230 -
Annals of Clinical and Translational... Jun 2024Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral...
OBJECTIVE
Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis.
METHODS
In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (n = 298; n = 49), serum neurofilament light chain (n = 117; n = 17), and respiratory tests (n = 93; n = 49).
RESULTS
Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91).
INTERPRETATION
Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.
PubMed: 38923228
DOI: 10.1002/acn3.52126 -
JAMA Network Open Jun 2024Poor sleep quality greatly impairs quality of life and accelerates deterioration in patients with Parkinson disease (PD), but current remedies remain limited.... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Poor sleep quality greatly impairs quality of life and accelerates deterioration in patients with Parkinson disease (PD), but current remedies remain limited. Acupuncture, used as an adjunctive therapy with anti-Parkinson medications, has shown positive effects in patients with PD. However, high-quality clinical evidence to support the effectiveness of acupuncture for patients with PD and poor sleep quality is lacking.
OBJECTIVE
To assess the safety and efficacy of real acupuncture (RA) vs sham acupuncture (SA) as an adjunctive therapy for patients with PD who have poor sleep quality.
DESIGN, SETTING, AND PARTICIPANTS
This single-center randomized clinical trial was performed at The First Affiliated Hospital of Guangzhou University of Chinese Medicine in China from February 18, 2022, to February 18, 2023. Patients with PD and sleep complaints were recruited and randomized (1:1) to receive RA or SA treatment for 4 weeks. Data analysis was performed from April 12 to August 17, 2023.
INTERVENTION
Treatment with RA or SA for 4 weeks.
MAIN OUTCOMES AND MEASURES
The main outcome was the change in Parkinson Disease Sleep Scale (PDSS) scores measured at baseline, after 4 weeks of treatment, and at 8 weeks of follow-up.
RESULTS
Of the 83 participants enrolled, 78 (94.0%) completed the intervention and were included in the analysis. Their mean (SD) age was 64.1 (7.9) years; 41 (52.6%) were men and 37 (47.4%) were women. A significant increase in PDSS scores from baseline was observed for both the RA group (29.65 [95% CI, 24.65-34.65]; P < .001) and the SA group (10.47 [95% CI, 5.35-15.60]; P < .001). Compared with the SA group, the RA group had a significant increase in PDSS scores after 4 weeks of treatment (19.75 [95% CI, 11.02-28.49]; P < .001) and at 8 weeks of follow-up (20.24 [95% CI, 11.51-28.98]; P < .001).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, acupuncture proved beneficial in improving sleep quality and quality of life among patients with PD. These findings suggest that the therapeutic effects of acupuncture could continue for up to 4 weeks.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2200060655.
Topics: Humans; Parkinson Disease; Female; Male; Acupuncture Therapy; Middle Aged; Aged; Sleep Quality; Quality of Life; Treatment Outcome; Sleep Wake Disorders; China
PubMed: 38922617
DOI: 10.1001/jamanetworkopen.2024.17862 -
Toxins Jun 2024Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The...
Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units ( = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.
Topics: Humans; Deep Brain Stimulation; Retrospective Studies; Male; Female; Dystonia; Middle Aged; Adult; Botulinum Toxins; Aged; Treatment Outcome; Quality of Life
PubMed: 38922176
DOI: 10.3390/toxins16060282 -
Tomography (Ann Arbor, Mich.) Jun 2024In recent years, Artificial Intelligence has been used to assist healthcare professionals in detecting and diagnosing neurodegenerative diseases. In this study, we...
In recent years, Artificial Intelligence has been used to assist healthcare professionals in detecting and diagnosing neurodegenerative diseases. In this study, we propose a methodology to analyze functional Magnetic Resonance Imaging signals and perform classification between Parkinson's disease patients and healthy participants using Machine Learning algorithms. In addition, the proposed approach provides insights into the brain regions affected by the disease. The functional Magnetic Resonance Imaging from the PPMI and 1000-FCP datasets were pre-processed to extract time series from 200 brain regions per participant, resulting in 11,600 features. Causal Forest and Wrapper Feature Subset Selection algorithms were used for dimensionality reduction, resulting in a subset of features based on their heterogeneity and association with the disease. We utilized Logistic Regression and XGBoost algorithms to perform PD detection, achieving 97.6% accuracy, 97.5% F score, 97.9% precision, and 97.7%recall by analyzing sets with fewer than 300 features in a population including men and women. Finally, Multiple Correspondence Analysis was employed to visualize the relationships between brain regions and each group (women with Parkinson, female controls, men with Parkinson, male controls). Associations between the Unified Parkinson's Disease Rating Scale questionnaire results and affected brain regions in different groups were also obtained to show another use case of the methodology. This work proposes a methodology to (1) classify patients and controls with Machine Learning and Causal Forest algorithm and (2) visualize associations between brain regions and groups, providing high-accuracy classification and enhanced interpretability of the correlation between specific brain regions and the disease across different groups.
Topics: Humans; Parkinson Disease; Magnetic Resonance Imaging; Male; Female; Machine Learning; Middle Aged; Aged; Algorithms; Brain
PubMed: 38921945
DOI: 10.3390/tomography10060068 -
Biomimetics (Basel, Switzerland) Jun 2024The brain is the most complex organ in the human body and, as such, its study entails great challenges (methodological, theoretical, etc.). Nonetheless, there is a... (Review)
Review
The brain is the most complex organ in the human body and, as such, its study entails great challenges (methodological, theoretical, etc.). Nonetheless, there is a remarkable amount of studies about the consequences of pathological conditions on its development and functioning. This bibliographic review aims to cover mostly findings related to changes in the physical distribution of neurons and their connections-the connectome-both structural and functional, as well as their modelling approaches. It does not intend to offer an extensive description of all conditions affecting the brain; rather, it presents the most common ones. Thus, here, we highlight the need for accurate brain modelling that can subsequently be used to understand brain function and be applied to diagnose, track, and simulate treatments for the most prevalent pathologies affecting the brain.
PubMed: 38921242
DOI: 10.3390/biomimetics9060362