Tremor Dominant Group Research Articles

TMS-evoked potentials unveil occipital network involvement in patients diagnosed with Parkinson’s disease within 5 years of inclusion

Distinguishing Parkinson’s disease (PD) subgroups may be achieved by observing network responses to external stimuli. We compared TMS-evoked potential (TEP) measures from stimulation of bilateral motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (V1) between 62 PD patients (age: 69.9 ± 7.5) and 76 healthy controls (age: 69.2 ± 4.3) using a TMS–EEG protocol. TEP measures were analyzed using two-way ANCOVA adjusted for MOCA. PD patients were divided into tremor dominant (TD), non-tremor dominant (NTD) and rapid disease progression (RDP) subgroups. PD patients showed lower wide-waveform adherence (wWFA) (p = 0.025) and interhemispheric connectivity (IHCCONN) (p < 0.001) compared to healthy controls. Lower occipital IHCCONN correlated with advanced disease stage (r = −0.37, p = 0.0039). The RDP and NTD groups showed lower wWFA in response to occipital stimulation than the TD group (p = 0.005). Occipital TEP measures identified RDP patients with 85% accuracy. These findings demonstrate occipital network involvement in early PD stages, suggesting that TEP measures offer insights into altered networks in PD subgroups.

Comorbidity of white matter lesions in parkinson's disease: a study on risk factors and phenotypic differences.

Comorbidity of white matter lesions (WMLs) in idiopathic Parkinson's disease (PD) is becoming increasingly common. To analyze the risk factors and phenotypic differences for the occurrence and severity of WMLs in patients with PD. A total of 123 PD patients underwent clinical, laboratory, and magnetic resonance imaging (MRI) evaluations. PD patients with WMLs were found to have a higher association with age, Modified Hoehn & Yahr stage (H-Y stage), and hypertension. There was a certain correlation between the severity of WMLs and PD phenotypes. 89% of PD patients had periventricular hyperintensities (PVH). Additionally, the score of the modified version of the Scheltens visual rating scale of PVH in the postural instability gait difficulty (PIGD) phenotype of PD was significantly higher than that in the tremor-dominant (TD) phenotype. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in the PIGD group were significantly lower than those in the TD group. Furthermore, compared with the TD group, the serum homocysteine level was significantly higher in the PIGD group. Age, H-Y stage, and hypertension are independent risk factors for WMLs in PD, and the severity of WMLs is related to the phenotype of PD patients. Our study found that PVH is the most common occurrence of WMLs in Parkinson's disease, and the burden of PVH is significantly higher in the PIGD phenotype compared to the TD phenotype of PD. Additionally, the PIGD phenotype is associated with more severe cognitive decline and elevated homocysteine levels.

Shear wave elastography characteristics of the gastrocnemius muscle in postural instability gait disorder vs tremor dominant Parkinson's disease patients.

This study explored the characteristics of muscle stiffness of lower gastrocnemius in resting and exercise states in patients with postural instability gait difficulty (PIGD) and tremor dominant (TD) Parkinson's disease patients using shear wave elastography (SWE). 75 PD patients from the Department of Parkinson's Disease Center in the Hospital from September 2021 to December 2022 were prospectively included, including 44 patients with PIGD and 31 with TD. In the same period, 40 healthy subjects matching gender and age were included as the control group. SWE was used to detect Young's modulus of both sides (right and left, R- and L-) of the lateral head of the gastrocnemius in resting (YM1) and exerciser states (YM2) in all participants and the absolute difference Young's modulus between resting and exercise state (ΔYM) was calculated. R-YM2 and R-ΔYM were the highest in the normal controls, followed by the TD group, and lowest in the PIGD group. There were no differences in L-YM2 and L-ΔYM between the PIGD group and the TD group (all p > 0.05), but they were lower than those in the normal control group (all p < 0.05). In addition, R-YM2 and R-ΔYM were negatively correlated with disease duration and UPDRS III scores in the PIGD group (all p < 0.05). R-ΔYM has the highest value in the differential diagnosis of PIGD and TD patients. The area under the receiver operating characteristic curve (ROC) curve is 0.812 (95%CI, 0.730-0.893), and the diagnostic threshold is 120.5 Kpa with a sensitivity of 63.6%, a specificity of 90.1%, a positive predictive of 80%, and a negative predictive value of 80%. Shear wave elastography is a sensitive ultrasound method for evaluating muscle strength in patients with PIGD and TD. It also provides a new biological indicator to distinguish between different phenotypes of patients with PD.

A comparison of quantitative parameters of axial posture and spinal mobility between motor subtypes of Parkinson's disease.

<p>Parkinson&rsquo;s disease (PD) is a heterogeneous neurodegenerative disorder characterized by contradictory clinical outcomes among its several subtypes. The disease can manifest with a tremor-dominant (TD) or a non-tremor-dominant (NTD) phenotype. Although the TD subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of axial symptoms. For this reason, in this study it was aimed to make a quantitative comparison of axial posture and spinal mobility between PD with TD and NTD.&nbsp;</p>. <p>This case-control study was conducted on 94 patients with diagnosed PD. A group diagnosis approach was used in the study, such that the diagnosis of each patient was confirmed, and they were assig-ned to TD and NTD groups by a neurologist expert on movement disorders. Of the patients with PD, 61 were in the TD group, and 33 were in the NTD group. Spinal mouse was used to measure spinal posture and spinal mobility in both sagittal and frontal planes.&nbsp;</p>. <p>Two groups of 61 patients (25 male + 36 female) with TD-PD (mean age: 64.49&plusmn;10.37 years) and 33 patients (20 male +13 female) with NTD-PD (mean age: 63.45&plusmn;9.11 years) were enrolled in the study. There were no significant differences bet&shy;ween the patients with TD and NTD in terms of sagittal and frontal postures (p&gt;0.05). In addition to this, anterior trunk tilt was found to significantly increase as the disease stage advanced in both groups. While the greatest anterior trunk tilt change in the TD-PD group was observed in the 3rd stage, NTD-PD group was in the 2.5th stage. Aside from this, the out&shy;comes of the spinal mobility measurements in the frontal and sagittal planes were similar between the groups (p&gt;0.05).</p>. <p>It is widely acknowledged that many clinical aspects of the TD and NTD forms of PD differ; however, in our study, it was observed that there may be no difference in the axial symptoms of the patients with PD in terms of classification according to tremor dominance.</p>.

Plasma GFAP as a prognostic biomarker of motor subtype in early Parkinson’s disease

Parkinson’s disease (PD) is a heterogeneous movement disorder with different motor subtypes including tremor dominant (TD), indeterminate and postural instability, and gait disturbance (PIGD) motor subtypes. Plasma glial fibrillary acidic protein (GFAP) was elevated in PD patients and may be regarded as a biomarker for motor and cognitive progression. Here we explore if there was an association between plasma GFAP and different motor subtypes and whether baseline plasma GFAP level can predict motor subtype conversion. Patients with PD classified as TD, PIGD or indeterminate subtypes underwent neurological evaluation at baseline and 2 years follow-up. Plasma GFAP in PD patients and controls were measured using an ultrasensitive single molecule array. The study enrolled 184 PD patients and 95 control subjects. Plasma GFAP levels were significantly higher in the PIGD group compared to the TD group at 2-year follow-up. Finally, 45% of TD patients at baseline had a subtype shift and 85% of PIGD patients at baseline remained as PIGD subtypes at 2 years follow-up. Baseline plasma GFAP levels were significantly higher in TD patients converted to PIGD than non-converters in the baseline TD group. Higher baseline plasma GFAP levels were significantly associated with the TD motor subtype conversion (OR = 1.283, P = 0.033) and lower baseline plasma GFAP levels in PIGD patients were likely to shift to TD and indeterminate subtype (OR = 0.551, P = 0.021) after adjusting for confounders. Plasma GFAP may serve as a clinical utility biomarker in differentiating motor subtypes and predicting baseline motor subtypes conversion in PD patients.

The Analysis of relation to brain iron deposition of Parkinson’s Disease using Quantitative Susceptibility Mapping

Objectives: This study aimed to investigate the levels of brain iron deposition in Parkinson's disease (PD) patients using Quantitative Susceptibility Mapping (QSM) and to determine whether distinctions compared to the general population exist. Furthermore, we examined potential variations in iron deposition among different PD subtypes.Methods: Structural brain imaging was conducted on 75 participants at Gangdong Kyung Hee University Hospital between August 2017 and May 2020. PD patients were categorized into Tremor Dominant (TD) and Postural Instability and Gait Difficulty (PIGD) subtypes. Voxel-based morphometry and QSM were employed to compare voxel-wise magnetic susceptibility across the entire brain between Normal Controls (NC) and PD groups. Subsequently, QSM values were compared between TD and PIGD groups.Results: QSM values were compared among 46 PD patients and 23 normal controls, as well as between TD (n=22) and PIGD (n=24) groups. Voxel-based QSM analysis revealed no significant differences between groups. Similarly, ROI-based QSM analysis showed no significant distinctions.Conclusions: No significant variations were observed between the PD patient group, NC group, or PD subtypes. This study systematically compared QSM values across a broad range of brain regions potentially linked to PD pathology. Additionally, the subdivision of the PD group into TD and PIGD subtypes for QSM-based iron deposition analysis represents a meaningful and innovative approach.

Application of sensory nerve quantitative tests to analyze the subtypes of motor disorders in Parkinson's disease.

This study investigated the sensory nerve function in people with different subtypes of Parkinson's disease (PD), which included the tremor-dominant (TD) group (n = 30), postural instability and gait disorder (PIGD) group (n = 33), and healthy-controls (HC) group (n = 33). Sural nerve's current perception threshold (CPT) and pain tolerance threshold (PTT) in both feet were measured at different frequencies. Results were evaluated using the mini-mental state examination (MMSE), Hoehn Yahr scale (H-Y) , and 3-meter timed-up-and-go-test (TUGT). The MMSE scores of the TD and HC groups were higher than those of the PIGD group (TD < HC). The 3-meter TUGT scores of the PIGD group were higher than theTD and HC groups (TD > HC). The PIGD patients experienced a significantly shorter disease duration and higher H-Y score than the TD patients ( P < 0.05). The values of 2 KHz CPT of left-side (CPTL), 2KHz CPT of right-side (CPTR), and 5 Hz CPTR in the PIGD group were significantly higher compared to the TD and HC groups ( P < 0.05, Bonferroni correction). Additionally, the values of 250 Hz CPTL, 5 Hz CPTL, 250 Hz CPTR, 2 kHz PTT of left-side (PTTL), 250 Hz PTTL, and 5 Hz PTTL in the PIGD group were significantly elevated relative to the TD group ( P < 0.05, Bonferroni correction). Distinctive current threshold perception and PTT of the sural nerve can be observed in patients with varying PD subtypes, and sensory nerve conduction threshold electrical diagnostic testing can detect these discrepancies in sensory nerve function.

Auto-Classification of Parkinson's Disease with Different Motor Subtypes Using Arterial Spin Labelling MRI Based on Machine Learning.

The purpose of this study was to automatically classify different motor subtypes of Parkinson's disease (PD) on arterial spin labelling magnetic resonance imaging (ASL-MRI) data using support vector machine (SVM). This study included 38 subjects: 21 PD patients and 17 normal controls (NCs). Based on the Unified Parkinson's Disease Rating Scale (UPDRS) subscores, patients were divided into the tremor-dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype. The subjects were in a resting state during the acquisition of ASL-MRI data. The automated anatomical atlas 3 (AAL3) template was registered to obtain an ASL image of the same size and shape. We obtained the voxel values of 170 brain regions by considering the location coordinates of these regions and then normalized the data. The length of the feature vector depended on the number of voxel values in each brain region. Three binary classification models were utilized for classifying subjects' data, and we applied SVM to classify voxels in the brain regions. The left subgenual anterior cingulate cortex (ACC_sub_L) was clearly distinguished in both NCs and PD patients using SVM, and we obtained satisfactory diagnostic rates (accuracy = 92.31%, specificity = 96.97%, sensitivity = 84.21%, and AUCmax = 0.9585). For the right supramarginal gyrus (SupraMarginal_R), SVM distinguished the TD group from the other groups with satisfactory diagnostic rates (accuracy = 84.21%, sensitivity = 63.64%, specificity = 92.59%, and AUCmax = 0.9192). For the right intralaminar of thalamus (Thal_IL_R), SVM distinguished the PIGD group from the other groups with satisfactory diagnostic rates (accuracy = 89.47%, sensitivity = 70.00%, specificity = 6.43%, and AUCmax = 0.9464). These results are consistent with the changes in blood perfusion related to PD subtypes. In addition, the sensitive brain regions of the TD group and PIGD group involve the brain regions where the cerebellothalamocortical (CTC) and the striatal thalamocortical (STC) loops are located. Therefore, it is suggested that the blood perfusion patterns of the two loops may be different. These characteristic brain regions could become potential imaging markers of cerebral blood flow to distinguish TD from PIGD. Meanwhile, our findings provide an imaging basis for personalised treatment, thereby optimising clinical diagnostic and treatment approaches.

Distinct changes in global brain synchronization in different motor subtypes of Parkinson's disease.

This study investigated alterations in degree centrality (DC) in different motor subtypes of Parkinson's disease (PD) and analyzed its clinical significance during disease occurrence. A total of 146 subjects were recruited in the study, including 90 patients with PD [51 and 39 with tremor dominant (TD) and akinetic-rigid dominant (ARD) disease, respectively] and 56 healthy controls (HCs). The resting-state functional magnetic resonance imaging data of all the subjects were obtained by 3.0 T magnetic resonance scans. The DC values, an indicator of whole brain synchronization, were calculated and compared among the TD, ARD, and HC groups. Disparities in DC values among the three groups were evaluated by analysis of variance and post hoc two-sample t-tests. Correlation between brain regions with DC differences and clinical variables were performed using partial correlation analysis after controlling for age, gender, and disease duration. Compared to the HCs, both TD and ARD groups demonstrated increased DC values bilaterally in the cerebellum; DC values were decreased in the left putamen and paracentral lobule in the TD group and in the left anterior cingulate gyrus and right supplementary motor area in the ARD group. Compared to the ARD group, the TD group showed decreased DC values in bilateral cerebellar hemispheres and increased DC values in the left anterior cingulate gyrus and right supplementary motor area. The DC of the whole brain showed inconsistencies and shared neural bases among patients with the two subtypes of PD. The differences between brain regions with abnormal DC values may be closely related to different clinical presentations of the two motor subtypes. Our findings provide new insights into the clinical heterogeneity of PD with respect to different motor subtypes.

Do motor subtypes of Parkinson’s disease impact the learning of motor tasks?

BACKGROUND:Previous studies have demonstrated that people with Parkinson's disease (PD) can acquire postural control skills even with the degeneration of motor areas responsible for consolidation of the representation regarding the learned motor skill in long-term memory. However, these findings have not considered the PD motor subtypes – tremor-dominant (TD), and postural instability and gait difficulty (PIGD). Although there is considerable heterogeneity in motor and non-motor symptoms between TD and PIGD, no study has addressed the effect of the PD subtype on learning postural control skills. AIM:We investigated the influence of PD motor subtypes on the learning of tasks with different postural control demands. METHOD:Fourteen individuals with PD (7 TD, 7 PIGD) practiced four motor tasks with high postural and cognitive demands. Participants completed 13 one-hour sessions (2x/week for 7 weeks). We considered the first and last practice sessions, pre-test and post-test, respectively. Also, we conducted one-week and one-month retention tests to assess performance persistence (motor learning). We assessed motor performance through the scores achieved on each motor task. RESULTS:Both groups demonstrated improvement in performance during the acquisition phase. However, the TD group outperformed the PIGD group in all motor tasks, despite both groups showing improvement in motor performance when comparing the results of pre-test with the post-test, and the improved performance was maintained in retention tests. The performance differences between groups are dissipated during consolidation, and they did not directly affect motor learning. INTERPRETATION: The TD and PIGD motor subtypes learned postural control tasks with different motor and cognitive demands.

Sudomotor deficits in Parkinson's disease with special reference to motor subtypes

IntroductionParkinson’s disease which shows clinically heterogeneous motor derangement may also accompany various autonomic disorders, but results of previous research on incidence and degree of each autonomic dysfunction have been inconsistent. As for sudomotor dysfunction, some investigators emphasize hypo- or anhidrois, whereas others stress hyperhidrosis. Subjects and methodsTo elucidate sudomotor dysfunctions in Parkinson’s disease (PD) with respect to subtypes, 225 clinically probable patients PD patients were stratified by motor phenotype (tremor-dominant group: 33; mixed group: 105; and akinesia-rigidity group: 87) and subjected to thermal and acetylcholine-induced (focal) sweating tests. Thermal sweating was qualitatively assessed with a modified version of Minor’s colorimetric methods. Thermoregulatory and acetylcholine-induced focal sweat rates were measured with capacitance hydrometers. ResultsThermoregulatory sweating was almost normal without anhidrotic area in 29.8% of PD patients, slightly defective in 38.7%, with anhidrotic area across <1/4 of the body surface, moderately defective in 22.2% with anhidrotic area across approximately 1/2 of the body surface, and extremely defective in 9.3% with anhidrotic area across more than 3/4 of the body surface. Patchy sweating was observed in 104 patients, implicating involvement of the hypothalamo-spinal and/or preganglionic systems in the disease process. Hyperhidrosis was seen in 15% of patients. Tremor-dominant group showed least impairment. ConclusionThis study suggests that PD is associated with various patterns and degree of sudomotor abnormalities, and that sudomotor sympathetic deficits may be related with the pathophysiology of akinesia and rigidity rather than that of resting tremor.

Altered Cerebral Vasoreactivity on Transcranial Color-Coded Sonography Related to Akinetic-Rigid Phenotype of Parkinson's Disease: Interim Analysis of a Cross-Sectional Study.

A correlation between worse functional outcomes in Parkinson's disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), on PD patients with different phenotypes of the disease and with risk factors for CVD. Idiopathic PD patients (n = 51) were divided into motor subtypes: Akinetic-rigid (AR) (n = 27) and Tremor-dominant (TD) (n = 24) and into two groups regarding vascular risk factors: when ≥2 were present (PDvasc) (n = 18) and <2 (PDnvasc) (n = 33). In a parallel analysis, the Fazekas scale on brain magnetic resonance imaging (MRI) was applied to a sample to assess the degree of leukoaraiosis. TCCS examinations were prospectively performed obtaining middle cerebral artery Mean Flow Velocities (Vm), Resistance Index (RI), and Pulsatility Index (PI). The Breath-Holding Index (BHI) was calculated to assess cerebrovascular reactivity (cVR). Standardized functional scales were administered (UPDRS III and Hoehn&Yahr). The phenotype groups were similar in age, disease duration and demographic parameters, but there were significantly higher H&Y scores than TD group. cVR was impaired in 66.7% of AR vs. 37.5% of TD. AR group exhibited lower BHI (0.53 ± 0.31 vs. 0.91 ± 0.62; p = 0.000), lower Vm after apnea (44.3 ± 9.0 cm/s vs. 53.4 ± 11.4 cm/s; p = 0.003), higher PI (0.91 ± 0.26 vs. 0.76 ± 0.12; p = 0.000) and RI (0.58 ± 0.11 vs. 0.52 ± 0.06; p = 0.021). PDvasc group showed higher PI (0.98 vs. 0.76; p = 0.001) and higher frequency of altered cVR (72.2% vs. 42.2%; p = 0.004). There was a significant predominance of higher values on Fazekas scale in the PDvasc group. We found no difference between the Fazekas scale when comparing motor subtypes groups but there was a trend toward higher scores in the AR phenotype. TCCS, a cost-effective method, displayed impaired cVR in Parkinsonian patients with risk factors for CVD with higher degree of MRI leukoaraiosis. PD patients with the AR disease phenotype also presented impaired cVR on TCCS and greater functional impairment, although with just a trend to higher scores on MRI Fazekas.

The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.

Updated Parkinson's disease motor subtypes classification and correlation to cerebrospinal homovanillic acid and 5-hydroxyindoleacetic acid levels

IntroductionMotor classifications of Parkinson's Disease (PD) have been widely used. This paper aims to update a subtype classification using the MDS-UPDRS-III and determine if cerebrospinal neurotransmitter profiles (HVA and 5-HIAA) differ between these subtypes in a cohort from the Parkinson's Progression Marker Initiative (PPMI). MethodsUPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a formula derived from UPDRS, and a new ratio was developed for subtyping patients with the MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping was correlated to neurotransmitter levels.Data were analyzed using receiver operating characteristic models and ANOVA. ResultsCompared to previous UPDRS classifications, the new MDS-UPDRS TD/AR ratios produced significant areas under the curve (AUC) for each subtype. The optimal sensitivity and specificity cutoff scores were ≥0.82 for TD, ≤0.71 for AR, and >0.71 and <0.82 for Mixed. Analysis of variance showed that the AR group had significantly lower HVA and 5-HIAA levels than the TD and HC groups. A logistic model using neurotransmitter levels and MDS-UPDRS-III could predict the subtype classification. ConclusionsThis MDS-UPDRS motor classification system provides a method to transition from the original UPDRS to the new MDS-UPDRS. It is a reliable and quantifiable subtyping tool for monitoring disease progression. The TD subtype is associated with lower motor scores and higher HVA levels, while the AR subtype is associated with higher motor scores and lower 5-HIAA levels.

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

ObjectiveThe 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).MethodsIn 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), β-amyloid 42 (Aβ42), and β-amyloid 40 (Aβ40) 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.ResultsIn the TD group, plasma NfL exhibited a significant association with MDS-UPDRS III and Montreal Cognitive Assessment (MoCA). A higher Aβ42/40 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 kPLI theta with HAMD and HAMA, especially in the prefrontal region, and kPLI 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 kPLI, and pairwise correlations were found among plasma NfL, theta TT, and MoCA scores in the TD group.ConclusionThese 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.

Olfactory dysfunction is associated with motor function only in tremor-dominant Parkinson's disease.

The prevalence of olfactory impairment in patients with Parkinson's disease (PD) is 50-90%, and therefore, olfactory dysfunction is one of the most prevalent non-motor symptoms (NMSs) in patients with PD. Numerous studies have evaluated the association between motor and non-motor symptoms and olfactory dysfunction in PD. In this study, we investigated the relationship between olfactory dysfunction, which is measured using the UPSIT test, with other motor and non-motor symptoms separately in three motor subtypes of PD, including tremor dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate and healthy subjects. We recruited 487 early-stage PD patients (43 PIGD, 406 TD, and 38 indeterminate) and healthy controls (HCs) (n = 197) from the Parkinson Progression Markers Initiative (PPMI). All participants completed motor and non-motor tests at baseline visit and after 4years of follow-up. Subjects underwent common PD scaling tests. Olfactory dysfunction was significantly correlated with declined motor functions only in the TD subtype. Also, significant correlations were noticed between olfactory dysfunction and speed-attention processing and executive function in the HCs as well. Finally, no significant or meaningful association was observed in the PIGD and indeterminate subtype. Anosmia and hyposmia subjects in the TD group had the worse motor and non-motor scores compared to normosmia subjects after 4years. Olfactory dysfunction was significantly correlated with declined motor functions in the TD subtype. This is indicating that olfactory dysfunction may be an early motor and non-motor biomarker only in the TD subtype. However, it is possible that the involvement of olfactory function in other subtypes is not strong enough to make it a useful marker of diseases progression.

24-hour ambulatory blood pressure alterations in patients with Parkinson's disease.

ObjectsAbnormal blood pressure (BP) regulation is a feature of autonomic dysfunction in Parkinson's disease (PD) patients. The present study was to analyze the BP alterations by 24‐h ambulatory BP monitoring in PD patients with different disease stages and subtypes.Methods32 consecutive patients PD patients and 43 control patients in our hospital from 2017 to 2020 were included. The circadian BP rhythm was divided into three types according to the 24‐h ambulatory BP monitoring. Dipping was defined as an average systolic BP (SBP) reduction during night‐time of 10%–19%. Reverse dipping was defined as an average increase in night‐time SBP values. The differences of the circadian BP rhythm and BP variability (BPV) were analyzed between PD group and the control group, the early PD group and the advanced PD group, as well as the tremor‐dominant group and the nontremor‐dominant group.ResultsThere was statistical difference in circadian BP rhythm between PD group and control group (p < .05). There were statistical differences in circadian BP rhythm between the early PD group and the advanced PD group (p < .05). The mean values of night‐time SBP and diastolic BP (DBP) in the advanced PD group were higher than those in the control group and the early PD group (p < .05). The DBP CV in the advanced PD group was higher than that in the control group and the early PD group (p < .05). There was no significant difference of circadian BP rhythm, mean BP, and BPV between the tremor‐dominant and the nontremor‐dominant PD group after matching the disease duration.ConclusionsReverse dipping was more common in PD patients in this study, especially in the advanced PD patients. 24‐h ambulatory BP monitoring is an important method to evaluate the BP alterations in PD patients. Clinicians should be alert to reverse dipping in PD patients and intervene to prevent serious clinical events.

Levodopa Challenge Test Predicts STN-DBS Outcomes in Various Parkinson's Disease Motor Subtypes: A More Accurate Judgment.

Background The relationship between the levodopa challenge test (LDCT) and postoperative subthalamic nucleus-deep brain stimulation (STN-DBS) benefits is controversial in patients with Parkinson's disease (PD). We aim to evaluate the value of total levodopa response (TLR) and symptom levodopa response (SLR) in predicting postoperative improvement in different PD motor subtypes. Methods Studies were split into a training set (147 patients) and a validation set (304 patients). We retrospectively collected data from 147 patients who received the Unified Parkinson's Disease Rating Scale- (UPDRS-) III and the Parkinson's Disease Questionnaire- (PDQ-) 39 evaluation. Patients were classified into tremor-dominant (TD), akinetic-rigid-dominant (AR), and mixed (MX) groups. Clinically important difference (CID) was employed to dichotomize DBS effects. For patients in each subtype group from the training set, we used the correlation and receiver operator characteristic (ROC) curve analyses to explore the strength of their relations. Areas under the curve (AUCs) were calculated and compared through the DeLong test. Results developed from the training set were applied into the validation set to predict postoperative improvement in different PD motor subtypes. Results In the validation cohort, TLR significantly correlated with postoperative motor (p < 0.001) and quality of life (QOL) (p < 0.001) improvement in the MX group. The AUC between TLR and UPDRS-III (TU) is 0.800. The AUC between TLR and PDQ-39 (TP) is 0.770. An associated criterion in both TU and TP is around 50%. In the AR group, strong correlation was only found in SLR and PDQ-39 (SP) (p < 0.001). And the AUC of SP is significantly larger than that in TLR and PDQ-39 (TP) (p = 0.034). An associated criterion in SP is around 37%. No significant correlation was found in the TD group. Conclusions We provide a more accurate judgment for LDCT. TLR strongly correlated with postoperative UPDRS-III and PDQ-39 improvement in MX patients. A TLR > 50% may indicate a higher possibility of clinically meaningful benefits from STN-DBS comparing to medication only. SLR can well predict QOL improvement in AR patients. Similarly, a SLR > 37% may indicate a higher possibility of clinically significant benefits from STN-DBS. LDCT provides limited information for TD patients.

Assessment of Force Production in Parkinson's Disease Subtypes.

Muscle weakness is a secondary motor symptom of Parkinson’s disease (PD), especially in the subtype characterized by postural instability and gait difficulty (PIGD). Since the PIGD subtype also presents worse bradykinesia, we hypothesized that it also shows a decreased rate of force development, which is linked to an increased risk of falling in PD. Therefore, we investigated the effects of PD and PD subtypes on a force production profile and correlated the force production outcomes with clinical symptoms for each PD subtype. We assessed three groups of participants: 14 healthy older adults (OA), 10 people with PD composing the PIGD group, and 14 people with PD composing the tremor-dominant group. Three knee extension maximum voluntary isometric contractions were performed in a leg extension machine equipped with a load cell to assess the force production. The outcome measures were: peak force and rate of force development (RFD) at 50 ms (RFD50), 100 ms (RFD100), and 200 ms (RFD200). We observed lower peak force, RFD50, RFD100, and RFD200 in people with PD, regardless of subtypes, compared with the OA group (p < 0.05 for all comparisons). Together, our results indicated that PD affects the capacity to produce maximal and rapid force. Therefore, future interventions should consider rehabilitation programs for people with PD based on muscle power and fast-force production, and consequently reduce the likelihood of people with PD falling from balance-related events, such as from an unsuccessful attempt to avoid a tripping hazard or a poor and slower stepping response.

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

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. 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. 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. 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.