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.

Detection of delirium in older patients-A point prevalence study in surgical and non-surgical hospital wards.

AIMS AND OBJECTIVES: To (i) determine the prevalence of delirium and identify delirium subtypes in surgical and non-surgical patients aged ≥65 years, (ii) determine whether certain precipitating factors affect the prevalence of delirium and (iii) review patients' medical records for description of delirium symptoms and the presence of International Classification of Diseases (ICD-10) coding for delirium in discharge summaries. METHODOLOGICAL DESIGN AND JUSTIFICATIONS: Despite being a robust predictor of morbidity and mortality in older adults, delirium might be inadequately recognised and under-reported in patients' medical records and discharge summaries. A point prevalence study (24-h) of patients ≥65 years from surgical and non-surgical wards was therefore conducted in a tertiary university hospital. ETHICAL ISSUES AND APPROVAL: The study was approved by the Data Protection Officer at the university hospital (2018/3454). RESEARCH METHODS, INSTRUMENTS AND/OR INTERVENTIONS: Patients were assessed for delirium with 4AT and delirium subtypes with the Delirium Motor Subtype Scale. Information about room transfers, need and use of sensory aids and medical equipment was collected onsite. Patients' medical records were reviewed for description of delirium symptoms and of ICD-10 codes. RESULTS: Overall, 123 patients were screened (52% female). Delirium was identified in 27% of them. Prevalence was associated with advanced age (≥85 years). The uncharacterised delirium subtype was most common (36%), followed by hypoactive (30%), hyperactive (24%) and mixed (9%). There were significant associations between positive screening tests and the need and use of sensory aids. Delirium symptoms were described in 58% of the patients who tested positive for delirium and the ICD-10 code for delirium was registered in 12% of these patients' discharge summaries. CONCLUSIONS: The high prevalence of delirium and limited use of discharge codes highlight the need to improve the identification of delirium in hospital settings and at discharge. Increased awareness and detection of delirium in hospital settings are vital to improve patient care.

Bispectral EEG (BSEEG) Algorithm Captures High Mortality Risk Among 1,077 Patients: Its Relationship to Delirium Motor Subtype.

OBJECTIVE: Delirium is dangerous and a predictor of poor patient outcomes. We have previously reported the utility of the bispectral EEG (BSEEG) with a novel algorithm for the detection of delirium and prediction of patient outcomes including mortality. The present study employed a normalized BSEEG (nBSEEG) score to integrate the previous cohorts to combine their data to investigate the prediction of patient outcomes. We also aimed to test if the BSEEG method can be applicable regardless of age, and independent of delirium motor subtypes. METHODS: We calculated nBSEEG score from raw BSEEG data in each cohort and classified patients into BSEEG-positive and BSEEG-negative groups. We used log-rank test and Cox proportional hazards models to predict 90-day and 1-year outcomes for the BSEEG-positive and -negative groups in all subjects and motor subgroups. RESULTS: A total of 1,077 subjects, the BSEEG-positive group showed significantly higher 90-day (hazard ratio 1.33 [95% CI 1.16-1.52] and 1-year (hazard ratio 1.22 [95% CI 1.06-1.40] mortality rates than the negative group after adjustment for covariates such as age, sex, CCI, and delirium status. Among patients with different motor subtypes of delirium, the hypoactive group showed significantly higher 90-day (hazard ratio 1.41 [95% CI 1.12-1.76] and 1-year mortality rates (hazard ratio 1.32 [95% CI 1.05-1.67], which remained significant after adjustment for the same covariates. CONCLUSION: We found that the BSEEG method is capable of capturing patients at high mortality risk.

Disease Progression in Multiple System Atrophy-Novel Modeling Framework and Predictive Factors.

BACKGROUND: Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course. OBJECTIVES: The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease. METHODS: The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated. RESULTS: The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression. CONCLUSIONS: The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Distribution of delirium motor subtypes in the intensive care unit: a systematic scoping review.

BACKGROUND: Delirium is the most common cerebral dysfunction in the intensive care unit (ICU) and can be subdivided into a hypoactive, hyperactive, or mixed motor subtype based on the clinical manifestation. The aim of this review was to describe the distribution, pharmacological interventions, and outcomes of delirium motor subtypes in ICU patients. METHODS: This systematic scoping review was performed according to the PRISMA-ScR and Cochrane guidelines. We performed a systematic search in six major databases to identify relevant studies. A meta-regression analysis was performed where pooled estimates with 95% confidence intervals were computed by a random effect model. RESULTS: We included 131 studies comprising 13,902 delirious patients. There was a large between-study heterogeneity among studies, including differences in study design, setting, population, and outcome reporting. Hypoactive delirium was the most prevalent delirium motor subtype (50.3% [95% CI 46.0-54.7]), followed by mixed delirium (27.7% [95% CI 24.1-31.3]) and hyperactive delirium (22.7% [95% CI 19.0-26.5]). When comparing the delirium motor subtypes, patients with mixed delirium experienced the longest delirium duration, ICU and hospital length of stay, the highest ICU and hospital mortality, and more frequently received administration of specific agents (antipsychotics, α2-agonists, benzodiazepines, and propofol) during ICU stay. In studies with high average age for delirious patients (> 65 years), patients were more likely to experience hypoactive delirium. CONCLUSIONS: Hypoactive delirium was the most prevalent motor subtype in critically ill patients. Mixed delirium had the worst outcomes in terms of delirium duration, length of stay, and mortality, and received more pharmacological interventions compared to other delirium motor subtypes. Few studies contributed to secondary outcomes; hence, these results should be interpreted with care. The large between-study heterogeneity suggests that a more standardized methodology in delirium research is warranted.

Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson's disease.

Purpose: This study is to investigate the relationship between thyroid function and Parkinson's disease (PD).Materials and Methods: Totally 77 PD patients were included, who were divided into tremor-dominant-type (TDT), akinetic-rigid-type (ART) and mixed-type (MXT) subgroups. Parkinsonism severity and stage was assessed by modified H-Y stage. Thyroid-stimulating hormone (TSH), fT3 and fT4 levels were detected to analyze thyroid function. Parameters of thyroid homeostasis, including thyroid's secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD) and Jostel's TSH index and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated and compared.Results: Thyroid hormone levels in PD patients were lower than normal controls. Patients with TDT/MXT had significantly higher fT4 level than those with ART. TSH levels were 1.73 ± 0.93 and 2.06 ± 1.04 ulU/ml for patients with TDT/MXT and ART, respectively. The patients in the TDT/MXT group had significantly lower SPINA-GD while significantly higher SPINA-GT than ART group. The fT3 level was significantly higher in early group than advanced group. TSH index in the early group was significantly higher than the advanced group. The fT4 level was negatively correlated with UPDRS motor score. Univariate and multivariable logistic regression analysis indicated that fT4 was positively correlated with PD motor subtype, which disappeared after adjusting for confounding factors. The fT3 level was negatively correlated with PD disease severity, even after adjusting for confounding factors. In female PD patients, fT4 level in TDT/MXT group was significantly higher than ART group. Male PD patients had higher fT4 levels in early patients than advanced patients. Percentage of patients exhibiting ART was decreased significantly in higher fT4 level subgroups. With the increase of TSH index and TTSI, the proportion of advanced PD patients gradually decreased. The proportion of PD patients with TDT/MXT motor subtype gradually increased with the quartiles of SPINA-GT.Conclusion: Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with PD.

Motor subtypes and other risk factors associated with drooling in Parkinson's disease patients.

OBJECTIVE: To explore the relationship between motor subtypes and drooling, and other risk factors associated with drooling in a large cohort of Chinese patients with Parkinson's disease (PD). METHODS: A total of 586 PD patients were enrolled in this study. Unified Parkinson's disease rating scale (UPDRS) and Hoehn & Yahr stage (H & Y stage) scale, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression-24 item (HRSD), and Mini-Mental State Examination (MMSE) were applied to all subjects. Salivary subscores of UPDRS part II were used to evaluate drooling. Constipation was diagnosed using the Rome III criteria. RESULTS: The prevalence of drooling in this cohort is 54.6% (320/586). Non-TD subtype PD patients tend to have higher daily levodopa-equivalent dose (LED), H & Y stage, UPDRS I, UPDRS II, and UPDRS III scores, HRSD score and ESS score, a higher percentage of levodopa treatment, drooling, dyskinesia, and constipation. After adjusting for confounders, non-TD subtype, male sex, UPDRS III score, ESS and PSQI scores, and constipation were still associated with drooling, with corresponding Odds ratios and 95% confidence intervals (95% CIs) were 1.865 (95% CI, 1.137-3.060), 1. 951 (95% CI, 1.326-2.869), 1.024 (95% CI, 1.002-1.046), 1.064 (95% CI, 1.024-1.105), 1.058 (95% CI, 1.000-1.119), and 1.603 (95% CI, 1.092-2.353), respectively. CONCLUSION: Drooling is common, even in mild-to-moderate PD patients. PD patients with non-TD subtype are at a higher risk of drooling. Male sex, motor severity, excessive daytime sleepiness, poor nighttime sleep, and constipation are also associated with drooling in patients with PD.

The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease.

INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms. METHODS: Patients with PD hospitalized in Neurology Department, Medical College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age) and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype. For homogeneity of the group patients with GBA mutation were excluded from the analysis. RESULTS: The ASN level did not differ between patients and HV (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes. There was inverse correlation between ASN and HY in PIGD subtype. CONCLUSIONS: Plasma ASN level is not valuable marker of the disease. It does not differ in subtypes of the disease. There is relation between plasma ASN level and the severity of the disease in PIGD subtype.

Parkinson Disease: The Relationship Between Non-motor Symptoms and Motor Phenotype.

BACKGROUND: Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothesized that the PIGD phenotype would be more likely to develop NMS, and that the non-dopamine-responsive axial signs would correlate with NMS severity. METHODS: We conducted a retrospective cross-sectional chart review to assess the relationship between NMS and PD motor phenotypes. PD patients were administered the NMS Questionnaire, the UPDRS-III, and the Mini-Mental State Examination score. The relationship between NMS burden and PD subtypes was examined using linear regression models. The prevalence of each NMS among difference PD motor subtypes was analyzed using chi-square test. RESULTS: PD patients with more advanced disease based on their UPDRS-III had higher NMS Questionnaire scores. The axial component of UPDRS-III correlated with higher NMS. There was no correlation between NMS and tremor scores. There was a significant correlation between PIGD score and higher NMS burden. PIGD group had higher prevalence in most NMS domains when compared with tremor dominant and indeterminate groups independent of disease duration and severity. CONCLUSIONS: NMS profile and severity vary according to motor phenotype. We conclude that in the PD population, patients with a PIGD phenotype who have more axial involvement, associated with advanced disease and poor motor response, have a higher risk for a higher NMS burden.

Resting-state functional connectivity of the occipital cortex in different subtypes of Parkinson's disease.

AIMS: To examine whether functional connectivity (FC) of the occipital gyrus differs between patients with Parkinson's disease (PD) motor subtypes and healthy controls (HCs). METHODS: We enrolled 30 PD patients exhibiting tremor dominance (TD), 43 PD patients with postural instability and gait disturbance (PIGD), and 42 HCs. The occipital gyrus was partitioned into six areas of interest, as seed points, via the Anatomical Automatic Labeling template to compare the FC of the three groups and analyze the relationship of FC with clinical scales. RESULTS: Compared with the PIGD group, the TD group showed increased FC between the left superior occipital gyrus (SOG.L) and right median cingulate and paracingulate gyri (DCG.R)/right paracentral lobule/bilateral inferior parietal, but supramarginal and angular gyri; the left middle occipital gyrus (MOG.L) and left posterior cingulate gyrus (PCG.L); the MOG.R and SOG.L/right calcarine fissure and surrounding cortex/DCG.R/PCG.L/right cuneus; the left inferior occipital gyrus (IOG.L) and right caudate nucleus; and the IOG.R and PCG.L. CONCLUSION: Differentiated FC between the occipital gyrus and other brain areas within the PD motor subtypes, which may serve as neural markers to distinguish between patients with TD and PIGD PD.

Causal associations between Helicobacter Pylori infection and the risk and symptoms of Parkinson's disease: a Mendelian randomization study.

Background: Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. Objective: To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). Methods: We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Results: Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; ß = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Conclusions: Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Structural and Functional Alterations of Motor-Thalamus in Different Motor Subtype of Parkinson's Disease: An Individual Study.

RATIONALE AND OBJECTIVES: This study aimed to investigate the structural and functional alterations occurring within bilateral premotor thalamus (mPMtha) in motor subtypes of Parkinson's disease (PD). MATERIALS AND METHODS: Sixty-one individuals with instability and gait difficulty (PIGD) subtype, 60 individuals with tremor-dominant (TD) subtype and 66 healthy controls (HCs) participated in the study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D T1-weighted (3DT1) scans. Functional connectivity (FC) analysis and Voxel-based morphometry (VBM) analysis were performed to evaluate the function and volume of mPMtha. Additionally, correlations between motor performance and FC values, volumes were examined separately. Support vector machine (SVM) model based on FC values and thalamic volumes was conducted to assist in the clinical diagnosis of PD motor subtype. RESULTS: Compared to HCs and PIGD, TD subtype showed increased FC between the bilateral mPMtha and left middle occipital gyrus, left inferior parietal lobule (IPL). While PIGD subtype demonstrated decreased FC between right mPMtha and precentral gyrus (PreCG), supramarginal, IPL and superior parietal lobule. FC of bilateral mPMtha with the identified regions were significantly correlated with motor performance scores in PD patients. The SVM classification based on FC values demonstrated a high level of efficiency (AUC=0.874). The volumes of the bilateral mPMtha were indifferent among three groups. CONCLUSION: We noted distinct FC alterations of mPMtha in TD and PIGD subtypes, and these changes were correlated with motor performance. Furthermore, the machine learning based on statistically significant FC might be served as an alternative approach for automatically classifying PD motor subtypes individually.

Distribution pattern of iron deposition in the basal ganglia of different motor subtypes of Parkinson's disease.

OBJECTIVE: The quantitative susceptibility mapping (QSM) technique was used to analyze the distribution pattern of iron deposition in the basal ganglia region of patients with motor subtypes of Parkinson's disease (PD) and to explore the difference in iron content in the basal ganglia region of PD motor subtypes on the major motor symptomatic side. METHODS: The study included 76 patients with PD and 37 healthy controls (HC). Patients with PD were divided into two groups: postural instability/gait disorder (PIGD)(n = 48), and tremor dominance (TD)(n = 28). We classified patients with PD according to the side of the major motor symptoms as left PIGD (n = 23), left TD (n = 14), right PIGD (n = 25), and right TD (n = 14). All subjects underwent brain magnetic resonance scanning to obtain QSM and susceptibility values in the corresponding regions of interest (ROI). RESULTS: (1) Compared with the HC, the bilateral SN in the PD-PIGD and TD group showed greater susceptibility values. The susceptibility values in the left CN, bilateral PUT were also greater in the PD-PIGD group than the HC. (2) Compared with the TD, the left PUT susceptibility values were greater in the PIGD group, especially in patients whose major symptomatic side were on the right limb. (3) Correlation analysis showed that in the PD group, bilateral SN was positively correlated with the unified Parkinson's disease rating scale III part scores of the Movement Disorder Society (MDS-UPDRS III) and the Hoehn-Yahr stage. Bilateral dentate nucleus (DN) susceptibility values were significantly positively correlated with TD scores, and left PUT susceptibility values were positively correlated with PIGD scores. The left SN within the PIGD group was positively correlated with the PIGD score. CONCLUSION: There were different iron deposition patterns in the basal ganglia between the PD-PIGD and TD groups. There also seems to be a difference in iron deposition in PD motor subtypes on different major motor symptom sides.

Association of Plasma and Electroencephalography Markers With Motor Subtypes of Parkinson's Disease.

Objective: The aim of this study was to investigate the correlations of plasma neurodegenerative proteins and electroencephalography (EEG) dynamic functional network (DFN) parameters with disease progression in early Parkinson's disease (PD) with different motor subtypes, including tremor-dominant (TD) and postural instability and gait disorder (PIGD). Methods: In our study, 33 patients with PD (21 TD and 12 PIGD) and 33 healthy controls (HCs) were enrolled. Plasma neurofilament light chain (NfL), α-synuclein (α-syn), total-tau (t-tau), ß-amyloid 42 (Aß42), and ß-amyloid 40 (Aß40) levels were measured using an ultrasensitive single-molecule array (Simoa) immunoassay. All the patients with PD underwent EEG quantified by DFN analysis. The motor and non-motor performances were evaluated by a series of clinical assessments. Subsequently, a correlation analysis of plasma biomarkers and EEG measures with clinical scales was conducted. Results: In the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aß42/40 level was significantly related to a decrease in Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) in the PIGD group. In terms of the correlation between EEG characteristic parameters and clinical outcomes, trapping time (TT) delta was positively correlated with MDS-UPDRS III and MoCA scores in the TD group, especially in the prefrontal and frontal regions. For other non-motor symptoms, there were significant direct associations of k PLI theta with HAMD and HAMA, especially in the prefrontal region, and k PLI gamma was particularly correlated with Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores in the prefrontal, frontal, and parietal regions in the TD group. Furthermore, there was a significant positive correlation between plasma t-tau and k PLI , and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group. Conclusion: These results provide evidence that plasma neurodegenerative proteins and EEG measures have great potential in predicting the disease progression of PD subtypes, especially for the TD subtype. A combination of these two kinds of markers may have a superposition effect on monitoring and estimating the prognosis of PD subtypes and deserves further research in larger, follow-up PD cohorts.

Delirium and Anxiety Outcomes Related to Visiting Policy Changes in the Intensive Care Unit During the COVID-19 Pandemic.

Objective: To evaluate the effect of intensive care unit (ICU) visit on the incidence of delirium, delirium subtype, and anxiety level in ICU patients. Methods: Trained psychiatrists and nurses evaluated ICU patients for delirium, delirium subtypes, and anxiety. Propensity score matching (PSM) was used to retrospectively analyze the data. Then, we compared the differences in the incidence of delirium, delirium subtypes, and anxiety level before and after the ICU visit ban. Logistic regression was conducted to identify the risk factors for delirium subtypes and high anxiety levels. Results: After PSM, there was no statistically significant difference in the incidence of delirium between the non-visiting and restrictive visiting groups (non-visiting 27.4% versus restrictive visiting 30.9%, p = 0.162). The proportion of hyperactive and mixed subtypes was higher in the non-visiting than in the restrictive visiting group (non-visiting 35.3 and 30.1% versus restrictive visiting 27.7 and 20.1%, p = 0.002). The anxiety level was higher in the non-visiting than in the restrictive visiting group (state-trait anxiety inventory score: non-visiting 53.46 ± 4.58 versus restrictive visiting 52.22 ± 6.50, p = 0.009). Patients who stayed in the ICU during the visit ban were more likely to have hyperactive (p = 0.005) and mixed subtype (p = 0.001) than those who did not. Moreover, patients who stayed in the ICU during the visit ban were more likely to experience high anxiety levels than those who did not (p < 0.001). Conclusion: Prohibition of ICU visits during COVID-19 pandemic did not affect the incidence of delirium during COVID-19 but could change the delirium subtype and raise anxiety level. Moreover, visiting prohibition was a risk factor for non-hypoactive delirium subtype and high anxiety levels. Therefore, ICU visits are important in dealing with delirium subtypes and anxiety in ICU patients.

Potential Usefulness of Blood Urea Nitrogen to Creatinine Ratio in the Prediction and Early Detection of Delirium Motor Subtype in the Intensive Care Unit.

Prediction and early detection of delirium can improve patient outcomes. A high blood urea nitrogen to creatinine ratio (BCR), which reflects dehydration, has been reported as a risk factor for delirium. Additionally, BCR represents skeletal muscle loss in intensive care unit (ICU) patients, which can have critical implications for clinical outcomes. We investigated whether BCR could be used to predict the occurrence and motor subtype of delirium in ICU patients through a retrospective cohort study that included 7167 patients (50 years or older) admitted to the ICU. Patients were assessed daily using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for ICU and categorized according to the delirium subtype. Participants were split into 10 groups according to BCR at ICU admission and the prevalence of each delirium subtype was compared. Multivariable logistic regression was then used for analysis. A higher BCR at ICU admission was associated with the development of hypoactive delirium. Moreover, BCR > 24.9 was associated with higher rates of hypoactive delirium. Our findings showed that a high BCR at ICU admission was associated with the development of hypoactive delirium, which suggested that BCR could be a potential biomarker for hypoactive delirium in ICU patients.

Prediction of Quality of Life in Patients With Parkinson's Disease With and Without Excessive Daytime Sleepiness: A Longitudinal Study.

Objective: There is a lack of longitudinal studies that directly compare the quality of life (QoL) and investigate the impact of clinical factors on QoL across different excessive daytime sleepiness (EDS) statuses in Parkinson's disease (PD); therefore, we aimed to compare QoL and reveal the potential heterogeneous predictors of QoL between patients with PD with and without EDS. Methods: We collected clinical data among 306 patients with PD over 2 years. EDS was assessed by the Epworth Sleepiness Scale and QoL was measured with the 39-item Parkinson's Disease Questionnaire. Results: We found that at both baseline and follow-up, patients with PD with EDS had poorer QoL and suffered more non-motor symptoms including depression and clinical probable rapid eye movement sleep behavior disorder (cpRBD). The generalized linear mixed model analysis indicated that the major predictors of QoL in PD with EDS were the akinetic-rigid type, disease duration, and total levodopa equivalent dose, while in PD without EDS, the primary determinants of QoL were Hoehn and Yahr, Mini-Mental State Examination (MMSE), and cpRBD. Conclusion: Patients with PD with EDS presented with poorer QoL. Besides, the baseline predictors of future QoL differed between patients with PD with and without EDS. These findings remind clinicians to target specific clinical factors when attempting to improve QoL among patients with PD.

Impact of motor subtype on non-motor symptoms and fall-related features in patients with early Parkinson's disease.

AIM: Clinical implications for motor phenotypes of Parkinson's disease (PD) remain to be further elucidated, particularly at the early stages of the disease. We aimed to compare the non-motor and fall-related features between tremor-dominant (TD) and postural instability-gait difficulty (PIGD) subtypes in patients with early PD. METHODS: PD was categorized into TD, intermediate and PIGD types, according to the literature. Not only motor symptoms, but also non-motor symptoms for global cognition, depression, anxiety, fatigue and dysautonomia, were measured in detail. In addition, fall-related features, including a previous history of falls, fear of fall measurement and gait freezing were assessed. RESULTS: In patients with early PD (disease duration no more than 5 years), 35 patients with TD-type PD and 31 patients with PIGD-type PD were finally evaluated for the study. Compared with the TD group, the PIGD group showed higher fatigue, gastrointestinal dysfunction and fall-related parameter scores. Moreover, the PIGD scores were significantly correlated with all of those symptoms. CONCLUSIONS: Our findings suggest that PIGD is significantly linked to fatigue, gastrointestinal dysfunction and fall-related features during the early stages of PD. Geriatr Gerontol Int 2021; 21: 416-420.

The inconsistency and instability of Parkinson's disease motor subtypes.

INTRODUCTION: Tremor-dominant (TD), indeterminate/mixed (ID/M) and postural instability gait difficulty/akinetic-rigid (PIGD/AR) are commonly used subtypes to categorize Parkinson's disease (PD) patients based on their most prominent motor signs. Three different algorithms to determine these motor subtypes are used. Here, we examined if PD subtypes are consistent among algorithms and if subtype stability over time depends on the applied algorithm. METHODS: Using a large longitudinal PD database, we applied 3 published algorithms of PD motor subtype classification in two sets of analyses: 1) cross-sectional analysis in 1185 patients, determining the prevalence of subtypes in 5-year intervals of disease duration; 2) longitudinal analysis of 178 patients, comparing subtypes of individual patients at baseline (within 5 years of diagnosis) and at follow-up ≥ 5 years after baseline. RESULTS: Cross-sectionally, prevalence of subtypes varied widely among the 3 algorithms: 5-32% TD, 9-31% ID/M, and 59-75% PIGD/AR. For all 3 algorithms, cross-sectional analysis showed a marked decline of TD prevalence with disease duration and a corresponding increase in PIGD/AR prevalence, driven by increasing gait/balance scores over time. Longitudinally, only 15-36% of baseline TD patients were still categorized as TD at 6.2 ± 1.0 years of follow-up. In 15-39% of baseline TD patients, the subtype changed to ID/M, and 46-50% changed to PIGD/AR. This shift was observed using all 3 algorithms. CONCLUSION: PD motor subtypes determined by different established algorithms are inconsistent and unstable over time. Lack of subtype fidelity should be considered when interpreting biomarker-subtype correlation and highlights the need for better definition of PD subtypes.