PD Symptoms Research Articles

DBS in the treatment of Parkinson’s disease

Purpose of the Study: This review examines the role of Deep Brain Stimulation (DBS) as a therapeutic intervention for advanced PD, focusing on indications, patient selection criteria, and potential complications. Materials and Methods: A comprehensive literature review was conducted, analyzing 37 studies from the PubMed database (English-language, up to October 2024) that assess the efficacy, safety, and long-term outcomes of DBS in managing advanced PD symptoms. Basic results: DBS has proven effective in enhancing motor function and quality of life in advanced PD cases. Although generally safe, DBS can present risks, including infections, dyskinesia, and psychiatric side effects. Conclusions: DBS is well known and constantly improving technology. Appropriate patient selection is essential; DBS is generally reserved for patients meeting specific criteria, including a confirmed PD diagnosis, disease duration of more than four years, a positive response to levodopa, and the absence of severe cognitive or unmanaged psychiatric disorders. Emerging research on genetic factors may enhance patient selection in the future.

Functional neural substrates of Parkinson’s disease and potential underpinnings of acute responses to acupuncture stimulation

Parkinson’s disease is a heterogenous neurodegenerative disorder with a wide variety of motor and non-motor symptoms. This study used resting-state fMRI to identify the neural substrates of PD and explore the acute neural response to acupuncture stimulation in 74 participants (50 patients with PD and 24 healthy controls). All participants with PD were evaluated for the severity of symptoms using the Unified Parkinson’s Disease Rating Scale and Balance Master. The z-transformed fractional amplitude of low-frequency fluctuation analysis showed significant differences between the PD and healthy controls in the cerebellar regions, which are thought to play a crucial role in PD pathology. Subsequently, seed-based functional connectivity of the cerebellum with the frontal, parietal, and limbic regions was identified as a potential diagnostic marker for PD. In addition, spontaneous neural activity in the precentral gyrus and thalamus was significantly associated with the severity of PD symptoms. Neural activity in the precentral gyrus, precuneus, and superior temporal gyrus showed a significant correlation with Balance Master indicators. Finally, acupuncture stimulation at GB34 significantly reduced the activity of the occipital regions in patients with PD, but this effect was not observed in healthy controls. The mixed-effects analysis revealed an interaction effects between group and acupuncture stimulation, suggesting that the modulatory effects of acupuncture could differ depending on disease status. Therefore, this study suggests the neural substrates of PD and potential underpinnings of acute neural response to acupuncture stimulation.

T2 MRI visible Perivascular Spaces in Parkinson`s Disease: clinical significance and association with polysomnography measured sleep.

Poor sleep quality might contribute to the risk and progression of neurodegenerative disorders via deficient cerebral waste clearance functions during sleep. In this retrospective cross-sectional study, we explore the link between enlarged perivascular spaces (PVS), a putative marker of sleep-dependent glymphatic clearance, with sleep quality and motor symptoms in Parkinson`s disease (PD) patients. T2-weighted MRI images of 20 patients and 17 healthy control subjects were estimated visually for PVS in the basal ganglia (BG) and centrum semiovale (CSO). The patient group additionally underwent a single-night polysomnography. Readouts included polsyomnographic sleep features and slow-wave activity (SWA), a quantitative EEG marker of sleep depth. Associations between PVS counts, PD symptoms (MDS-UPDRS scores) and sleep parameters were evaluated using correlation and regression analyses. Intra- and inter-rater reproducibility was assessed with weighted Cohen`s kappa coefficient. BG and CSO PVS counts in both patients and controls did not differ significantly between groups. In patients, PVS in both brain regions were negatively associated with SWA (1-2Hz) (BG: r(15)=-0.58, padj=0.015 and CSO: r(15)=-0.6, padj=0.015). Basal ganglia PVS counts were positively associated with motor symptoms of daily living (IRR=1.05, CI [1.01, 1.09], p=0.007, padj=0.026) and antidepressant use (IRR=1.37, CI [1.05, 1.80], p=0.021, padj=0.043) after controlling for age. Centrum Semiovale PVS counts in patients were positively associated with a diagnosis of REM sleep behaviour disorder (IRR=1.39, CI [1.06 , 1.84]), p=0.018, padj=0.11). These results add evidence that sleep deterioration may play a role in impairing glymphatic clearance via altered perivascular function, potentially contributing to disease severity in PD patients.

Diagnostic and therapeutic challenges in PD-associated non-motor symptoms: the roles of neurologists and consultant physicians.

In addition to their motor symptoms, almost all Parkinson's disease patients report non-motor symptoms (NMS) and, in the later course of the disease, non-motor fluctuations as well. These NMS encompass e.g. neuropsychiatric, gastrointestinal, urogenital, cardiovascular symptoms and pain. For a long time, these symptoms received no or at best very little attention, but there is a growing trend towards their recognition and treatment. Despite this progress, significant gaps remain, particularly due to the sometimes-limited expertise among neurologists regarding these symptoms. The clinical need to consequently treat these NMS raises the question of whether Movement Disorder specialists should and can address them sufficiently or if additional consultant physicians have to be enrolled. Therefore, our objective is to establish benchmarking criteria to outline a potential way forward. Ideally, Movement Disorder specialists should take on greater responsibility when treating non-motor PD symptoms, integrating diagnostic and therapeutic pathways from other medical disciplines where feasible.

Patient Experience and Feasibility of a Remote Monitoring System in Parkinson's Disease.

Remote monitoring systems have the potential to measure symptoms and treatment effects in people with Parkinson's disease (PwP) in the home environment. However, information about user experience and long-term compliance of such systems in a large group of PwP with relatively severe PD symptoms is lacking. The aim was to gain insight into user experience and long-term compliance of a smartwatch (to be worn 24/7) and an online dashboard to report falls and receive feedback of data. We analyzed the data of the "Bringing Parkinson Care Back Home" study, a 1-year observational cohort study in 200 PwP with a fall history. User experience, compliance, and reasons for noncompliance were described. Multiple Cox regression models were used to identify determinants of 1-year compliance. We included 200 PwP (mean age: 69 years, 37% women), of whom 116 (58%) completed the 1-year study. The main reasons for dropping out of the study were technical problems (61 of 118 reasons). Median wear time of the smartwatch was 17.5 h/day. The online dashboard was used by 77% of participants to report falls. Smartphone possession, shorter disease duration, more severe motor symptoms, and less-severe freezing and balance problems, but not age and gender, were associated with a higher likelihood of 1-year compliance. The 1-year compliance with this specific smartwatch was moderate, and the user experience was generally good, except battery life and data transfer. Future studies can build on these findings by incorporating a smartwatch that is less prone to technical issues.

Manganese exposure leads to depressive-like behavior through disruption of the Gln–Glu–GABA metabolic cycle

There is a correlation between long-term manganese (Mn) exposure and the Parkinson's-like disease (PD), with depression as an early symptom of PD. However, the direct relationship between Mn exposure and depression, and the mechanisms involved, remain unclear. We found that Mn exposure led to depressive-like behavior and mild cognitive impairment in mice, with Mn primarily accumulating in the cornu ammonis 3 (CA3) area of the hippocampus. Mice displayed a reduction in neuronal dendritic spines and damage to astrocytes specifically in the CA3 area. Spatial metabolomics revealed that Mn downregulated glutamic acid decarboxylase 1 (GAD1) expression in astrocytes, disrupting the Glutamine-Glutamate-γ-aminobutyric acid (GlnGluGABA) metabolic cycle in the hippocampus, leading to neurotoxicity. We established an in vitro astrocyte Gad1 overexpression (OEX) model and found that the cultured medium from Gad1 OEX astrocytes reversed neuronal synaptic damage and the expression of gamma-aminobutyric acid (GABA) related receptors. Using the astrocyte Gad1 OEX mouse model, results showed that OEX of Gad1 ameliorated depressive-like behavior and cognitive dysfunction in mice. These findings provide new insight into the important role of GAD1 mediated GlnGluGABA metabolism disorder in Mn exposure induced depressive-like behavior. This study offers a novel sight to understanding abnormal emotional states following central nervous system damage induced by Mn exposure.

Mapping knowledge domain of acupuncture for Parkinson's disease: a bibliometric and visual analysis.

This study points to probing the inclination and mapping knowledge domain of acupuncture for Parkinson's disease through bibliometrics. A search was conducted on 1 February 2024 using the Web of Science to identify papers published on acupuncture for Parkinson's disease. The analysis included scientific research, countries, organizations, authors/cited authors, keywords, journals, and cited references. Bibliometric data were analyzed using VOSviewer software, CiteSpace, GraphPad Prism, and Scimago Graphica. The studies on acupuncture for Parkinson's disease were visualized as a network map according to the publication year. The cumulative publication trend on acupuncture for Parkinson's disease is increasing year by year. China is the leading contributor in this field. International collaboration is predominantly concentrated in Europe, while institutional collaboration is chiefly limited to Chinese universities specializing in traditional Chinese medicine. Park HJ is the most prolific author, with "Movement Disorders" being the journal with the most publications. "Brain Research" is identified as a key journal, reflecting a focus on neuroscience. Kim SN is the most cited author, while Eisenberg DM is a prominent author in this field. Research topics such as mouse models, systematic reviews, and non-motor symptoms are frequently explored, with messenger RNA of substantia nigra emerging as a notable keyword in this field. Choi YG's 2009 paper, published in the Neuroscience Letters journal, is a critical reference in this field. Key papers include Eisenberg DM's 1998 study on randomized trials of acupuncture for non-motor symptoms of PD, as well as research focusing on the neuroinflammatory regulatory mechanisms of acupuncture for PD. The bibliometric analysis offers an exhaustive generality of the advancement and worldwide trends in acupuncture treatments for Parkinson's disease, shedding light on potential avenues for prospective research.

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study.

If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS. We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias. Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

Diagnostic and Statistical Manual of Mental Disorders, fifth edition, personality disorders and the alternative model: Prediction of naturalistically observed behavior, interpersonal functioning, and psychiatric symptoms, 1 year later.

Traditional personality disorders (PDs; e.g., Diagnostic and Statistical Manual of Mental Disorders, fifth edition [DSM-5] Section II PDs), as well as dimensional traits (e.g., alternative model for PD [AMPD]), offer unique advantages in personality pathology assessment. However, very little is known about how these systems compare in predicting observable behavior. This study compares self-report ratings of PD symptoms (i.e., Structured Clinical Interview for DSM-IV PD) with self-reports of AMPD traits (i.e., Personality Inventory for DSM-5) in predicting clinical outcomes, 1 year later, via three different methods: (a) naturalistically observed psychosocial functioning (i.e., electronically activated recorder [EAR]), (b) informant-reported interpersonal functioning (i.e., Inventory of Interpersonal Problems-32), and (c) self-reported suicidality (SI), depression, anxiety, and substance use symptoms (i.e., Psychiatric Diagnostic Screening Questionnaire). Data were analyzed from 72 individuals in current or recent psychiatric treatment meeting diagnosis for at least one PD. Results showed that DSM Section II PD and AMPD ratings yielded meaningful and comparable predictions of naturalistically observed EAR variables and informant-rated interpersonal functioning. The AMPD appeared to offer slight advantages in the prediction of EAR-observed negative affect, hostile words, and informant-rated interpersonal functioning, with clearer advantages at the facet level. Overall, these results provide tentative evidence that both DSM Section II PD and AMPD systems show meaningful links with clinical outcomes measured via multiple methods 1 year later, but with clearer advantages for the AMPD at the facet level. Moreover, results show that the EAR is a viable method for capturing naturalistically observed clinically meaningful, in vivo behavior of individuals exhibiting maladaptive personality patterns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy of cognitive behavioral therapy for anxiety and depression in Parkinson’s disease patients: an updated systematic review and meta-analysis

BackgroundParkinson’s disease (PD) patients often experience non-motor symptoms like depression and anxiety, significantly impacting their quality of life. With the limited effectiveness of pharmacological treatments, effective non-pharmacological interventions are needed. This systematic review and meta-analysis aimed to evaluate the efficacy of cognitive-behavioral therapy (CBT) in reducing depression and anxiety symptoms in PD patients.MethodsRandomized controlled trials (RCTs) exploring CBT's effectiveness for depression and anxiety in PD patients were included. Studies published until April 2023 were identified from PubMed, Web of Science, and Scopus. Methodological quality was assessed using the Risk of Bias-2 (ROB-2) tool. Statistical analysis involved calculating the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) using Review Manager 5.4.1.ResultsThe systematic review included 12 studies involving 241 PD patients. CBT led to a substantial reduction in anxiety (SMD -0.95, 95% CI [-1.15 to -0.74], P < 0.00001) and depression (SMD -1.02, 95% CI [-1.39 to -0.65], P < 0.0001). Both traditional CBT and tele-CBT (administered over the phone or internet) were effective in treating depression and anxiety. Traditional CBT improved depression (SMD -1.16, 95% CI [-1.83 to -0.49], P < 0.00001), while tele-CBT showed comparable results (SMD -0.90, 95% CI [-1.31 to -0.48], P < 0.00001). For anxiety, both traditional CBT (SMD -0.94, 95% CI [-1.25 to -0.63], P < 0.00001) and tele-CBT (SMD -0.95, 95% CI [-1.22 to -0.67], P < 0.00001) significantly reduced symptoms.In conclusion, this systematic review and meta-analysis demonstrated the efficacy of CBT in reducing depression and anxiety in PD patients. Healthcare providers are encouraged to integrate CBT into their treatment protocols. However, additional high-quality studies with longer-term follow-up assessments are needed to further enhance understanding in this area.Prospero RegistrationCRD42023424758.

Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol

BackgroundParkinson’s disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD.Methods/Design: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction.DiscussionThis trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD.Trial registrationClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

Habenula volume change in Parkinson's disease: A 7T MRI study

ObjectiveParkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and early non-motor symptoms. The habenula is implicated in the pathophysiology of depression. This study investigates habenular volume in PD patients without clinical depression to show the changes in PD unrelated to depression. MethodsThe study used high-resolution 7 Tesla MRI data from the TRACK-PD study involving 104 PD patients and 44 healthy controls (HCs). The habenula was manually segmented, and volumes were measured, considering demographic data and depression scores via the Beck Depression Inventory (BDI). ResultsNo significant correlation was found between habenular volume and BDI scores in PD patients or HCs. However, the PD group exhibited a significantly larger mean and right habenular volume than HCs. Although PD patients showed higher BDI scores, indicating more subthreshold depression, these did not correlate with the habenular volume. ConclusionThe results suggest that while the habenula may be involved in the symptoms of PD, its role in depression within this cohort is unclear. The changes might be related to the role of the habenula in motor symptoms. This study provides a new perspective on the role of the habenula in PD, but future research could lead to a greater understanding of the neuroanatomical features of the habenula in PD.

Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5–45 Hz). Average peri‑stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13–45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Continuous and Unconstrained Tremor Monitoring in Parkinson's Disease Using Supervised Machine Learning and Wearable Sensors.

Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson's disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge. We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques. Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88. We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson's disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life.

The greater loss of ability to detect unpleasant smells may be related to the risk of more severe PD symptoms

The greater loss of ability to detect unpleasant smells may be related to the risk of more severe PD symptoms

Subthalamic nucleus but not entopeduncular nucleus deep brain stimulation enhances neurogenesis in the SVZ-olfactory bulb system of Parkinsonian rats.

Deep brain stimulation (DBS) is a highly effective treatment option in Parkinson's disease. However, the underlying mechanisms of action, particularly effects on neuronal plasticity, remain enigmatic. Adult neurogenesis in the subventricular zone-olfactory bulb (SVZ-OB) axis and in the dentate gyrus (DG) has been linked to various non-motor symptoms in PD, e.g., memory deficits and olfactory dysfunction. Since DBS affects several of these non-motor symptoms, we analyzed the effects of DBS in the subthalamic nucleus (STN) and the entopeduncular nucleus (EPN) on neurogenesis in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. In our study, we applied five weeks of continuous bilateral STN-DBS or EPN-DBS in 6-OHDA-lesioned rats with stable dopaminergic deficits compared to 6-OHDA-lesioned rats with corresponding sham stimulation. We injected two thymidine analogs to quantify newborn neurons early after DBS onset and three weeks later. Immunohistochemistry identified newborn cells co-labeled with NeuN, TH and GABA within the OB and DG. As a putative mechanism, we simulated the electric field distribution depending on the stimulation site to analyze direct electric effects on neural stem cell proliferation. STN-DBS persistently increased the number of newborn dopaminergic and GABAergic neurons in the OB but not in the DG, while EPN-DBS does not impact neurogenesis. These effects do not seem to be mediated via direct electric stimulation of neural stem/progenitor cells within the neurogenic niches. Our data support target-specific effects of STN-DBS on adult neurogenesis, a putative modulator of non-motor symptoms in Parkinson's disease.

Parkinson’s Detection Using Voice Features and Spiral Drawings

Parkinson's is a dynamic neurodegenerative disease that presents multiple symptoms that advance over time. Our project proposes an innovative Parkinson's discovery machine learning model that combines both voice examination and spiral drawings assessments to capture numerous angles of the disease's symptomatology. Our approach looks for developing a comprehensive Parkinson’s detection model over different stages and symptoms of the disease. By integrating voice analysis techniques to discern subtle changes in speech patterns and spiral drawing assessments to evaluate motor function, our method aims to provide a more holistic assessment of PD symptoms. By leveraging the complementary strengths of voice analysis and spiral drawing assessments, our proposed PD detection project aims to overcome the limitations of existing approaches and provide clinicians with a more comprehensive model for early detection, diagnosis and monitoring of Parkinson's Disease. Ultimately, this initiative strives to enhance patient outcomes, improve treatment efficacy, and advance our understanding of PD progression.

Systematic analysis of the relationship between intestinal microbiota and neurological disorders: emerging perspective in neurogastroenterology

By the complex gut-brain axis, the gut microbiota (GM) has a critical role in neurological function. The complex link between several neurological illnesses and the gut microbiota (GM) is examined in this comprehensive study. Strong evidence has been found, based on a review of the literature from 2019 to 2024, connecting GM dysbiosis to the etiology and development of conditions such as epilepsy, multiple sclerosis, Alzheimer's disease, autism spectrum disorder, stroke, and amyotrophic lateral sclerosis (ALS). In these cases, GM changes increase disease severity, interfere with immune responses, and worsen neuroinflammation. In particular, dysbiosis affects the prevalence of autoimmune encephalomyelitis in MS and adds to motor impairment and gastrointestinal symptoms in PD. Via pro-inflammatory microorganisms, dysregulated GM in AD exacerbates neurodegeneration. Moreover, the gut-brain axis influences emotion, behavior, and cognition, all of which are impacted by the development of ASD. In epilepsy, GM dysbiosis affects inflammatory responses and seizure frequency; in ALS, it leads to neuroinflammation and motor neuron degeneration. Notwithstanding noteworthy discoveries, the dearth of randomized controlled trials presents obstacles, requiring more mechanistic clarification and investigation of microbiota-targeted treatments for neurological disorders.

The Impact of Fatigue on Sleep and Other Non-Motor Symptoms in Parkinson's Disease.

case-control study in which 131 PD patients and 131 age- and sex-matched controls were enrolled. Main characteristics of fatigue, sleep, and other non-motor symptoms were assessed using specific validated questionnaires. According to the Chalder fatigue scale, fatigue is more prevalent in PD patients (38.16%) compared to healthy controls (26.71%). Fatigue was identified in 46.54% of the PD patients using the Parkinson's Fatigue Scale (PFS-16). PD patients with fatigue presented a worse motor status, more sleep disturbances (insomnia, daytime sleepiness), a broader spectrum of non-motor symptoms (pain, anxiety, urinary disturbances), worse cognitive performances, a lower level of happiness, and worse quality of life compared to PD patients without fatigue. Fatigue is a common symptom of PD and needs to be assessed, considering its consequences on quality of life. Sleep disturbances have a great influence over fatigue in PD patients.

The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.