Therapeutic and Diagnostic Implications of Carbon Dot: An Advancement in the Avenue towards Cancer, Diabetes and Neurodegenerative Disorders.

INTRODUCTION: Carbon dots (CDs), by virtue of their electrical and optical properties, emit intense light and fluorescence. They have attributes like photostability, high quantum yield (QY), high emission, and scalability. In the recent past, theranostic-CDs have been widely used in sensing, imaging, and medication administration. Furthermore, CDs may provide significant promise to detect and ability to cross blood-brain barrier (BBB) along with a drug to treat numerous neurodegenerative disorders (ND), such as Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis. METHOD: This review aims at exploring the immense utility of CDs in the arena of theranostics. The immense utility of CDs was investigated through a systematic exploration of previously published data in the relevant field. The application of CDs is well extended to treat life-threatening disorders, like diabetes and cancer. In order to keep harmful substances out of the brain, the blood- -brain barrier (BBB) forms a defensive barrier. RESULTS: Water and gases being simple molecules can traverse the BBB without getting filtered out, but several large molecules suffer to reach the site of action owing to their poor solubility. CDs have recently been employed for delivering drugs to the brain and to assess the central nervous system. An in-depth study of relevant literature indicates that CDs are the next-generation carrier with an innate potential to subside the drawbacks of conventional nanoparticles. CONCLUSION: This review illustrates several biomedical applications of CDs, primarily focusing on neurological illnesses, diabetes, and cancers. It also confers the usefulness of CDs in diagnostic imaging.

Optimal Preservation of PFFs in Glycerol Enhances Suitability for Modeling Parkinson's Disease.

Injecting α-synuclein pre-formed fibrils (αSyn PFFs) into various tissues and organs involves converting monomeric αSyn into a fibrillar form, inducing extensive αSyn pathology that effectively models Parkinson's disease (PD). However, the distinct physicochemical properties of αSyn amyloid fibrils can potentially reduce their seeding activity, especially during storage. In this study, it is demonstrated that αSyn PFFs exhibit significant sensitivity to low temperatures, with notable denaturation occurring between -20 and 4 °C, and gradual disassembly persisted even under storage conditions at -80 °C. To mitigate this issue, a commonly used protein stabilizer, glycerol is introduced, which significantly reverses the cold-induced disassembly of PFFs. Remarkably, storing PFFs with 20% glycerol at -80 °C for a month preserved their morphology and seeding activity as freshly prepared PFFs. Glycerol-stabilized αSyn PFFs resulted in compromised neuronal survival, with the extent of these impairments correlating with the formation of αSyn pathology both in vivo and in vitro, indistinguishable from freshly prepared PFFs. Storing sonicated PFFs with 20% glycerol at -80 °C provides an optimal storage method, as sonication is necessary for activating their seeding potential. This approach reduces the frequency of sonication, simplifies handling, and ultimately lowers the overall workload, enhancing the practicality of using PFFs.

Role of the video head impulse test in the evaluation of vestibulo-ocular reflex in individuals with Parkinson's disease.

Background and purpose:

Parkinson’s disease (PD) is the most common movement disorder and the second most common neu­rodegenerative disease of the central ner­vous system. Dizziness is frequently reported by PD patients, yet there is a paucity of research focusing on the vestibulo-ocular reflex (VOR) in this population using high-frequency vestibular testing. This study aims to investigate the VOR in individuals with PD using the video head thrust test with and without suppression. 

Forty individuals with PD and 40 healthy individuals were included in the study. According to the Hoehn-Yahr Scale, individuals with PD were defined as early stage with a score of 1–2.5 and middle to late stage with a score of 3 to 5. The Head Impulse Testing Paradigm (HIMP) and Suppression Head Impulse Testing Paradigm (SHIMP) were applied to all individuals.

No statistically significant difference was observed between the PD group and the control group in terms of semicircular canal (SCC) gains in both HIMP and SHIMP tests. No catch-up saccades were observed in the right anterior, right posterior, left anterior, and left posterior SCC planes in the PD and control groups. However, in the right lateral SCC plane 32 patients in the PD group had saccades, while 8 patients in the control group had saccades. In the left lateral SCC plane, 32 patients in the PD group and 9 patients in the control group had catch-up saccades. A statistically significant difference was observed in the number and amplitude of saccades in the right and left lateral SCC planes compared to the control group (p<0.05). In addition, in the PD group, the amplitude, peak velocity, and latency of the anticompensatory saccades seen in SHIMP showed a statistically significant difference compared to the control group (p<0.05).

VOR in the vertical SCC plane was not affected in individuals with PD. However, VOR in the lateral SCC plane was affected. It was concluded that when evaluating VOR with both HIMP and SHIMP in individuals with PD, the presence of catch-up saccades should be focused on and evaluated for possible vestibular dysfunction, even though SCC gains are normal. This study will contribute to a deeper understanding of vestibular function in PD, potentially informing better management strategies for dizziness in this population. 

Impact of Preoperative Cognition on Motor Improvement in Bilateral Subthalamic Nucleus-Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: This study aimed to assess the influence of preoperative cognition on postoperative motor and nonmotor outcomes in patients with Parkinson disease (PD) after deep brain stimulation (DBS). MATERIALS AND METHODS: A retrospective study was performed in subjects with PD with bilateral subthalamic DBS. Preoperative cognition was indexed by Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and global neuropsychological evaluation (NPE) scores. The primary outcome was change from baseline to postoperative off-drug Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part 3 score. Secondary outcomes included change from baseline to postoperative MDS-UPDRS part 1 subscores. RESULTS: The study included 226 subjects; 176 patients (77.9%) had normal cognition (PD-NC); 48 (21.2%) had mild cognitive impairment (MCI), and two (0.9%) had PD dementia. Proportional change (-41.4% vs -52.2%, p = 0.013) in off-drug MDS-UPDRS part 3 score was smaller in PD-MCI than in PD-NC. PD-CRS (Pearson's r = 0.236, p < 0.001) and NPE (Pearson's r = 0.219, p < 0.001) scores displayed a positive correlation with proportional change in off-drug MDS-UPDRS part 3 score. Worse PD-CRS scores were related to larger improvements in MDS-UPDRS part 1.2 (hallucinations) (Pearson's r = 0.135, p = 0.045). CONCLUSIONS: DBS induces a clinically meaningful motor improvement in patients with cognitive impairment and PD, but the improvement may be smaller than in patients who are not cognitively affected. Further research into the risk-benefit balance of DBS in people with PD and cognitive dysfunction is warranted.

Effect of deep brain stimulation on sexual dysfunction among patients who had Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Patients who have Parkinson's disease (PD) present several non-motor issues, such as sexual dysfunction. Deep brain stimulation (DBS) is a great treatment for PD and could affect both motor and non-motor symptoms of patients. AIM: The main goal of the current study is to evaluate the impact of DBS on the sexual dysfunction among patients with PD. METHODS: Five databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library) were searched for records. Studies that measured the effect of DBS sexual function were included. The risk of bias assessment tool of non-randomized studies of interventions (ROBINS-I) was used to assess the quality of the included studies. The before and after data extraction and statistical analysis were performed using the Comprehensive Meta-analysis software (CMA) version 3.0. RESULT: Ten studies were included in the systematic review; six of them were eligible to perform a meta-analysis with a total sample size of 532 participants and a mean age of 62.21 ± 1.59 years. All participants performed STN-DBS. The sexual function of participants after STN-DBS implantation significantly increased (SMD = -0.124, 95% CI: -0.209 to -0.038, P-value = 0.005). It also did not have any publication bias. Additionally, their quality of life mounts significantly (SMD = -0.712, 95% CI: -1.002 to -0.422, p-value <0.001). CONCLUSION: Our systematic review highlights the potential effect of STN-DBS on reducing the sexual dysfunction of patients with PD and boosting their quality of life.

Modeling of Parkinson's Disease in Different Models.

Parkinson's Disease (PD) is a progressive disorder worldwide and its etiology remains unidentified. Over the last few decades, animal models of PD have been extensively utilized to explore the development and mechanisms of this neurodegenerative condition. Toxic and transgenic animal models for PD possess unique characteristics and constraints, necessitating careful consideration when selecting the appropriate model for research purposes. Animal models have played a significant role in uncovering the causes and development of PD, including its cellular and molecular processes. These models suggest that the disorder arises from intricate interplays between genetic predispositions and environmental influences. Every model possesses its unique set of strengths and weaknesses. This review provides a critical examination of animal models for PD and compares them with the features observed in the human manifestation of the disease.

Clinical efficacy of low-intensity pulsed ultrasound in Parkinson's disease with cognitive impairment.

OBJECTIVE: Low-intensity pulsed ultrasound (LIPUS), is a new technique for invasive brain stimulation and modulation that has emerged recently, but the effects in Parkinson's disease with cognitive impairment (PD-CI) have been less observed. In this study, we collected 56 patients with PD-CI who were continuously treated with LIPUS for 8 weeks, and observed the clinical efficacy of LIPUS on PD-CI patients by comparing with the Sham stimulation continuous treatment. METHODS: Fifty-six PD-CI patients were divided into the Sham group (given Sham stimulation on top of conventional medication, n = 28) and the LIPUS group (given LIPUS stimulation on top of conventional medication, n = 28), and both groups continued treatment for 8 weeks. Post-treatment efficacy and pre- and post-treatment cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)], emotional state [Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI)], quality of life [Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39)], and serologic indices [5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA)] were compared. RESULTS: The total effective rate of the LIPUS group was higher versus that of the Sham group. In both groups, MMSE and MoCA scores increased; BDI and BAI scores decreased; UPDRS and PDQ-39 scores were reduced; the levels of 5-HT, NE, and DA were elevated. The above changes were more pronounced in the LIPUS group (all P < 0.05). CONCLUSION: The application of LIPUS on PD-CI could ameliorate patients' cognitive function, emotional state and quality of life, and regulate and optimize neurotransmitter expression levels.

Genetic architecture of a single cohort of 230 Indian Parkinson's Disease patients.

INTRODUCTION: Indian Parkinson's Disease (PD) patients are severely underrepresented in terms of genetic studies and little is known about the frequency of variants and their impact on motor and nonmotor symptoms (NMS). METHODS: This retrospective cross-sectional study was conducted in PD patients undergoing treatment at a tertiary care hospital from India. Patients were advised genetic testing if they had (i) age at onset (AAO) of motor symptoms at or before 50 years (EOPD), (ii) positive family history of PD, parkinsonism or dystonia. All patients underwent whole exome sequencing and potentially pathogenic variants were identified. RESULTS: Clinical and genetic data were available for 230 (163 males, 70.4 %) patients. Thirty-five pathogenic and likely pathogenic variants in various PD genes were identified in 47 patients resulting in a yield of 20.4 %. In the remaining, 82 patients had either variants of uncertain significance or had variants in genes not associated with parkinsonism and 101 patients did not have any non-benign variants. Patients with genetically mediated PD had a lower AAO and statistically greater frequency of dystonia (36.2 %), postural instability (29.8 %) and mood disorder (29.8 %) and a higher Hoehn and Yahr score (2.9). Among the 47 patients, 11 patients had PARK-PRKN, six patients had PARK-PLA2G6, and 22 patients had PARK-GBA1. CONCLUSION: Around one-fifth of early-onset PD can have an underlying monogenetic cause. PARK-GBA1, PARK-PRKN and PARK-PLA2G6 are the commoner causes of genetically mediated PD in India. Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia.

A review article on the development of dopaminergic neurons and establishment of dopaminergic neuron-based in vitro models by using immortal cell lines or stem cells to study and treat Parkinson's disease.

The primary pathological hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, a critical midbrain region. In vitro models based on DA neurons provide a powerful platform for investigating the cellular and molecular mechanisms of PD and testing novel therapeutic strategies. A deep understanding of DA neuron development, including the signalling pathways and transcription factors involved, is essential for advancing PD research. This article first explores the differentiation and maturation processes of DA neurons in the midbrain, detailing the relevant signalling pathways. It then compares various in vitro models, including primary cells, immortalized cell lines, and stem cell-based models, focusing on the advantages and limitations of each. Special attention is given to the role of immortalized and stem cell models in PD research. This review aims to guide researchers in selecting the most appropriate model for their specific research goals. Ethical considerations and clinical implications of using stem cells in PD research are also discussed.

Bio-inspired feature selection for early diagnosis of Parkinson's disease through optimization of deep 3D nested learning.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders that affect the quality of human life of millions of people throughout the world. The probability of getting affected by this disease increases with age, and it is common among the elderly population. Early detection can help in initiating medications at an earlier stage. It can significantly slow down the progression of this disease, assisting the patient to maintain a good quality of life for a more extended period. Magnetic resonance imaging (MRI)-based brain imaging is an area of active research that is used to diagnose PD disease early and to understand the key biomarkers. The prior research investigations using MRI data mainly focus on volume, structural, and morphological changes in the basal ganglia (BG) region for diagnosing PD. Recently, researchers have emphasized the significance of studying other areas of the human brain for a more comprehensive understanding of PD and also to analyze changes happening in brain tissue. Thus, to perform accurate diagnosis and treatment planning for early identification of PD, this work focuses on learning the onset of PD from images taken from whole-brain MRI using a novel 3D-convolutional neural network (3D-CNN) deep learning architecture. The conventional 3D-Resent deep learning model, after various hyper-parameter tuning and architectural changes, has achieved an accuracy of 90%. In this work, a novel 3D-CNN architecture was developed, and after several ablation studies, the model yielded results with an improved accuracy of 93.4%. Combining features from the 3D-CNN and 3D ResNet models using Canonical Correlation Analysis (CCA) resulted in 95% accuracy. For further enhancements of the model performance, feature fusion with optimization was employed, utilizing various optimization techniques. Whale optimization based on a biologically inspired approach was selected on the basis of a convergence diagram. The performance of this approach is compared to other methods and has given an accuracy of 97%. This work represents a critical advancement in improving PD diagnosis techniques and emphasizing the importance of deep nested 3D learning and bio-inspired feature selection.

System biology-based assessment of the molecular mechanism of IMPHY000797 in Parkinson's disease: a network pharmacology and in-silico evaluation.

IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, IMPHY000797 derivatives have been found to modulate such genes involved in multiple neurological disorders. Hence, this study seeks to identify such genes and the probable molecular mechanism that could be involved in the pathogenesis of Parkinson's disease. The study utilized various biological tools such as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4.2, Schrodinger suite, ClueGo, and GUSAR. All the reported genes were obtained using DisGeNET, and further, the common genes were incorporated into the STRING to get the KEGG pathway, and all the data was converted to a protein/pathway network via Cytoscape. The clustering of the genes was performed for the gene-enriched data using two-sided hypergeometrics (p-value). The binding affinity of the IMPHY000797 was verified with the highest regulated 25 proteins via utilizing the "Monte Carlo iterated search technique" and the "Emodel and Glide score" function. Three thousand five hundred eighty-three genes were identified for Parkinson's disease and 31 genes for IMPHY000797 compound, among which 25 common genes were identified. Further, the "FOXO-signaling pathway" was identified to be a modulated pathway. Among the 25 proteins, the highest modulated genes and highest binding affinity were exhibited by SIRT3, FOXO1, and PPARGC1A with the compound IMPHY000797. Further, rat toxicity analysis provided the efficacy and safety of the compound. The study was required to identify the probable molecular mechanism, which needs more confirmation from other studies, which is still a significant hit-back.

Association between neutrophil-to-lymphocyte ratio and motor subtypes in idiopathic Parkinson's disease: a prospective observational study.

BACKGROUND: Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. METHODS: This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. RESULTS: A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1ßand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1ß in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1ß plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1ß was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1ß showed better performance in identifying the AR motor subtype. CONCLUSION: NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD.

α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson's disease.

BACKGROUND: Pathological accumulation of aggregated α-synuclein (aSYN) is a common feature of Parkinson's disease (PD). However, the mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. A potentially relevant target of aSYN is the mitochondrion. To test this hypothesis, genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain. METHODS: aSYN PFFs were stereotaxically injected into the SNc or PPN of mice. Twelve weeks later, mice were studied using a combination of approaches, including immunocytochemical analysis, cell-type specific transcriptomic profiling, electron microscopy, electrophysiology and two-photon-laser-scanning microscopy of genetically encoded sensors for bioenergetic and redox status. RESULTS: In addition to inducing a significant neuronal loss, SNc injection of PFFs induced the formation of intracellular, phosphorylated aSYN aggregates selectively in dopaminergic neurons. In these neurons, PFF-exposure decreased mitochondrial gene expression, reduced the number of mitochondria, increased oxidant stress, and profoundly disrupted mitochondrial adenosine triphosphate production. Consistent with an aSYN-induced bioenergetic deficit, the autonomous spiking of dopaminergic neurons slowed or stopped. PFFs also up-regulated lysosomal gene expression and increased lysosomal abundance, leading to the formation of Lewy-like inclusions. Similar changes were observed in PPN cholinergic neurons following aSYN PFF exposure. CONCLUSIONS: Taken together, our findings suggest that disruption of mitochondrial function, and the subsequent bioenergetic deficit, is a proximal step in the cascade of events induced by aSYN pathology leading to dysfunction and degeneration of neurons at-risk in PD.

Parietal memory network and memory encoding versus retrieval impairments in PD-MCI patients: A hippocampal volume and cortical thickness study.

OBJECTIVE: The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF). METHODS: The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (N = 18) and EF (N = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation. RESULTS: Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p⟨0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p⟨0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (p > 0.05). CONCLUSION: Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment.

Precision Imaging in Neurodegeneration: The Superiority of Diffusion Tensor Imaging Over Conventional MRI in Differentiating Parkinson's Disease From Atypical Parkinsonian Syndromes.

Background Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor and non-motor symptoms. Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP) and essential tremor (ET), present with overlapping clinical features, making differential diagnosis challenging. Conventional MRI has limitations in distinguishing PD from APS, necessitating advanced imaging techniques like diffusion tensor imaging (DTI) for more accurate diagnosis. Objectives This retrospective study aimed to evaluate the diagnostic accuracy of DTI in diagnosing PD and APS, particularly assessing its ability to differentiate these conditions from each other compared to conventional MRI. Additionally, the study sought to determine if DTI could diagnose PD in cases where conventional MRI results were normal, thereby highlighting the potential role of DTI in enhancing diagnostic precision in neurodegenerative disorders. Methodology The study included 30 patients with clinically diagnosed PD or APS who underwent both conventional MRI and DTI. Data were collected retrospectively. Imaging was performed using a Philips Multiva 1.5-Tesla MRI scanner (Philips, Amsterdam, Netherlands). DTI sequences were analyzed for fractional anisotropy (FA) values in the substantia nigra, superior cerebellar peduncle, middle cerebellar peduncle, transverse pontine fibers, and dentate nucleus. The FA values were compared with established normal values, and the findings from DTI were correlated with clinical diagnoses and conventional MRI results. Results Among the 30 patients, 53.3% were clinically diagnosed with PD and 46.7% with APS, including PSP and ET. Conventional MRI findings were normal in 46.7% of cases, indicating its limitations in detecting early or subtle changes in neurodegenerative disorders. In contrast, DTI identified abnormalities in 83.3% of cases, demonstrating its superior diagnostic sensitivity. DTI detected significant FA value reductions in the substantia nigra in PD patients (mean FA: 0.440), which is consistent with the degeneration of dopaminergic neurons characteristic of PD. In PSP patients, the superior cerebellar peduncle showed marked FA reductions (mean FA: 0.523), correlating with the clinical features of PSP, such as bradykinesia and postural instability. ET was identified by reduced FA values in the superior cerebellar peduncle and dentate nucleus, distinguishing it from other forms of parkinsonism. DTI was particularly effective in cases where conventional MRI results were inconclusive or normal, identifying early-stage PD and differentiating it from APS with greater accuracy. The study demonstrated a sensitivity of 95.8% and specificity of 93.8% for DTI in differentiating PD from APS compared to conventional MRI. Conclusion This study highlights DTI as a superior imaging modality for the early diagnosis and differentiation of parkinsonian disorders, particularly when conventional MRI results are inconclusive. DTI's ability to detect significant microstructural changes in specific brain regions, evidenced by FA value reductions, enhances diagnostic accuracy. Incorporating DTI into routine clinical practice is essential for accurate differentiation between PD and APS, facilitating better patient management.

Examining Agreement in Psychotic Symptom Assessment: Insights from Parkinson's Disease Dementia Dyads.

BACKGROUND: Psychosis and cognitive decline often co-occur in Parkinson's Disease (PD), which complicates assessment. OBJECTIVE: We measured agreement between patients with PD and dementia (PDD) and care partners (CPs) in their independent evaluation of PD-related psychotic symptoms. METHODS: We compared responses to a PD psychosis rating scale (SAPS-PD) in 21 dyads of patients with PDD and cognitively normal CPs. We assessed the concordance of responses using the intraclass correlation coefficient (ICC). Following the psychosis assessment, the clinician used all available information and adjudicated who provided the most reliable responses. RESULTS: Dyads demonstrated poor concordance in summary scores (ICC = 0.464). Six of the nine individual items had poor agreement. The clinician adjudicated the patient's response as the more reliable in 71.4% of cases. CONCLUSIONS: Although many psychotic symptoms are internal and not observable, in the context of PDD, both patient and CP inputs are valuable, but final adjudication favors patient responses.

Spiral volumetric optoacoustic tomography of reduced oxygen saturation in the spinal cord of M83 mouse model of Parkinson's disease.

PURPOSE: Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson's disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of the transgenic M83 murine model of PD overexpressing the mutated A53T alpha-synuclein form in comparison with non-transgenic littermates. METHODS: In vivo spiral volumetric optoacoustic tomography (SVOT) was performed to assess oxygen saturation (sO2) in the spinal cords of M83 mice and non-transgenic littermates. Ex vivo high-field T1-weighted (T1w) magnetic resonance imaging (MRI) at 9.4T was used to assess volumetric alterations in the spinal cord. 3D SVOT analysis and deep learning-based automatic segmentation of T1w MRI data for the mouse spinal cord were developed for quantification. Immunostaining for phosphorylated alpha-synuclein (pS129 α-syn), as well as vascular organization (CD31 and GLUT1), was performed after MRI scan. RESULTS: In vivo SVOT imaging revealed a lower sO2SVOT in the spinal cord of M83 mice compared to non-transgenic littermates at sub-100 µm spatial resolution. Ex vivo MRI-assisted by in-house developed deep learning-based automatic segmentation (validated by manual analysis) revealed no volumetric atrophy in the spinal cord of M83 mice compared to non-transgenic littermates at 50 µm spatial resolution. The vascular network was not impaired in the spinal cord of M83 mice in the presence of pS129 α-syn accumulation. CONCLUSION: We developed tools for deep-learning-based analysis for the segmentation of mouse spinal cord structural MRI data, and volumetric analysis of sO2SVOT data. We demonstrated non-invasive high-resolution imaging of reduced sO2SVOT in the absence of volumetric structural changes in the spinal cord of PD M83 mouse model.

Feasibility Study of Parkinson's Speech Disorder Evaluation With Pre-Trained Deep Learning Model for Speech-to-Text Analysis.

Objective: This study investigates the feasibility of employing a pre-trained deep learning wave-to-vec model for speech-to-text analysis in individuals with speech disorders arising from Parkinson's disease (PD). Methods: A publicly available dataset containing speech recordings including the Hoehn and Yahr (H&Y) staging, Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part I, UPDRS Part II scores, and gender information from both healthy controls (HC) and those diagnosed with PD was utilized. Employing the Wav2Vec model, a speech-to-text analysis method was implemented on PD patient data. Tasks conducted included word letter classification, word match probability assessment, and analysis of speech waveform characteristics as provided by the model's output. Results: For the dataset comprising 20 cases, among individuals with PD, the H&Y score averaged 2.50±0.67, the UPDRS II-part 5 score averaged 0.70±1.00, and the UPDRS III-part 18 score averaged 0.80±0.98. Additionally, the number of words derived from decoded text subsequent to speech recognition was evaluated, resulting in mean values of 299.10±16.79 and 259.80±93.39 for the HC and PD groups, respectively. Furthermore, the calculated degree of agreement for all syllables was based on the speech process. The accuracy for the reading sentences was observed to be 0.31 and 0.10, respectively. Conclusion: This study aimed to demonstrate the effectiveness of wave-to-vec in enhancing speech-to-text analysis for patients with speech disorders. The findings could pave the way for the development of clinical tools for improved diagnosis, evaluation, and communication support for this population.

Towards full remote programming for deep brain stimulation in Parkinson's disease: A case series.

People with Parkinson's disease (PwPD) who undergo deep brain stimulation (DBS) surgery could benefit from remote programming (RP), which has proven to be both effective and economical. However, there is limited research on PwPD with DBS implants who have completed all programming sessions exclusively through remote means (full remote programming, FRP). This case report documents the experiences of five PwPD who underwent FRP, with four demonstrating improvements in motor symptoms, quality of life, and medication reduction. A total of 22 postoperative programming sessions were conducted, all via RP. FRP integrates RP with online consultations. Our findings contribute preliminary evidence supporting the feasibility and safety of FRP in the postoperative care of PwPD with DBS implants.