Postural Instability Gait Difficulty Score Research Articles

Disease Progression of Data-Driven Subtypes of Parkinson's Disease: 5-Year Longitudinal Study from the Early Parkinson's Disease Longitudinal Singapore (PALS) Cohort.

The detailed trajectory of data-driven subtypes in Parkinson's disease (PD) within Asian cohorts remains undisclosed. To evaluate the motor, non-motor symptom (NMS) progression among the data-driven PD clusters. In this 5-year longitudinal study, NMS scale (NMSS), Hospital Anxiety Depression Scale (HADS), and Epworth sleepiness scale (ESS) were carried out annually to monitor NMS progression. H& Y staging scale, MDS-UPDRS part III motor score, and postural instability gait difficulty (PIGD) score were assessed annually to evaluate disease severity and motor progression. Five cognitive standardized scores were used to assess detailed cognitive progression. Linear mixed model was performed to assess the annual progression rates of the longitudinal outcomes. Two hundred and six early PD patients, consisting of 43 patients in cluster A, 98 patients in cluster B and 65 subjects in cluster C. Cluster A (severe subtype) had significantly faster progression slope in NMSS Domain 3 (mood/apathy) score (p = 0.01), NMSS Domain 4 (perceptual problems) score (p = 0.02), NMSS Domain 7 (urinary) score (p = 0.03), and ESS Total Score (p = 0.04) than the other two clusters. Cluster A also progressed significantly in PIGD score (p = 0.04). For cognitive outcomes, cluster A deteriorated significantly in visuospatial domain (p = 0.002), while cluster C (mild subtype) deteriorated significantly in executive domain (p = 0.04). The severe cluster had significantly faster progression, particularly in mood and perceptual NMS domains, visuospatial cognitive performances, and postural instability gait scores. Our findings will be helpful for clinicians to stratify and pre-emptively manage PD patients by developing intervention strategies to counter the progression of these domains.

Reorganization of structural brain networks in Parkinson’s disease with postural instability/gait difficulty

The Postural Instability/Gait Difficulty (PIGD) subtype of Parkinson’s disease (PD) has a faster disease progression, a higher risk of cognitive and motor decline, yet the alterations of structural topological organization remain unknown.Diffusion Tensor Imaging (DTI) and 3D-TI scanning were conducted on 31 PD patients with PIGD (PD-PIGD), 30 PD patients without PIGD (PD-non-PIGD) and 35 Healthy Controls (HCs). Structural networks were constructed using DTI brain white matter fiber tractography. A graph theory approach was applied to characterize the topological properties of complex structural networks, and the relationships between significantly different network metrics and motor deficits were analyzed within the PD-PIGD group.PD-PIGD patients exhibited increased shortest path length compared with PD-non-PIGD and HCs (P < 0.05, respectively). Additionally, PD-PIGD patients exhibited decreased nodal properties, mainly in the cerebellar vermis, prefrontal cortex, paracentral lobule, and visual regions. Notably, the degree centrality of the cerebellar vermis was negatively correlated with the PIGD score (r = −0.390; P = 0.030) and Unified Parkinson’s Disease Rating Scale Part III score (r = −0.436; P = 0.014) in PD-PIGD patients. Furthermore, network-based statistical analysis revealed decreased structural connectivity between the prefrontal lobe, putamen, supplementary motor area, insula, and cingulate gyrus in PD-PIGD patients.Our findings demonstrated that PD-PIGD patients existed abnormal structural connectomes in the cerebellar vermis, frontal-parietal cortex and visual regions. These topological differences can provide a topological perspective for understanding the potential pathophysiological mechanisms of PIGD in PD.

Altered connectivity between frontal cortex and supplementary motor area in various types of Parkinson's disease.

Tremor-dominant (TD) and postural instability/gait difficulty (PIGD) are common subtypes of Parkinson's disease, each with distinct clinical manifestations and prognoses. The neural mechanisms underlying these subtypes remain unclear. This study aimed to investigate the altered connectivity of the frontal cortex and supplementary motor area (SMA) in different types of Parkinson's disease. Data of 173 participants, including 41 TD patients, 65 PIGD patients, and 67 healthy controls, were retrospectively analyzed. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical assessments. Differences in amplitude of low frequency fluctuation (ALFF), voxel-wise functional connectivity (FC), and functional network connectivity (FNC) among the three groups were compared, followed by partial correlation analysis. Compared to healthy controls, the left dorsolateral superior frontal gyrus (DLSFG) ALFF was significantly increased in both PIGD and TD patients. The FC between the left DLSFG and the left SMA, as well as between the left paracentral lobule and the right DLSFG, was significantly decreased. Similarly, the FNC between the visual network and the auditory network was reduced. Compared to TD patients, PIGD patients showed a significantly higher ALFF in the left DLSFG and a notably reduced FC between the left DLSFG and left SMA. Additionally, the FC of the left DLSFG-SMA was inversely correlated with the PIGD score exclusively in PIGD patients. The FNC of the visual-auditory network was inversely associated with the tremor score only in TD patients. Decreases in the left DLSFG-SMA connectivity may be a key feature of the PIGD subtype, while reduced VN-AUD connectivity may characterize the TD subtype.

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

IntroductionThe 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. MethodsSixty-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. ResultsThe 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. ConclusionThese 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.

Cholinergic basal forebrain system degeneration underlies postural instability/gait difficulty and attention impairment in Parkinson's disease.

The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system. A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free-water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses. Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006). Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive-motor interaction.

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson's disease.

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease. A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated. The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05). 11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes\xa0of Parkinson\u2019s disease in the MARK-PD study

The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson’s Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.

Predicting Axial Impairment in Parkinson's Disease through a Single Inertial Sensor.

Background: Current telemedicine approaches lack standardised procedures for the remote assessment of axial impairment in Parkinson’s disease (PD). Unobtrusive wearable sensors may be a feasible tool to provide clinicians with practical medical indices reflecting axial dysfunction in PD. This study aims to predict the postural instability/gait difficulty (PIGD) score in PD patients by monitoring gait through a single inertial measurement unit (IMU) and machine-learning algorithms. Methods: Thirty-one PD patients underwent a 7-m timed-up-and-go test while monitored through an IMU placed on the thigh, both under (ON) and not under (OFF) dopaminergic therapy. After pre-processing procedures and feature selection, a support vector regression model was implemented to predict PIGD scores and to investigate the impact of L-Dopa and freezing of gait (FOG) on regression models. Results: Specific time- and frequency-domain features correlated with PIGD scores. After optimizing the dimensionality reduction methods and the model parameters, regression algorithms demonstrated different performance in the PIGD prediction in patients OFF and ON therapy (r = 0.79 and 0.75 and RMSE = 0.19 and 0.20, respectively). Similarly, regression models showed different performances in the PIGD prediction, in patients with FOG, ON and OFF therapy (r = 0.71 and RMSE = 0.27; r = 0.83 and RMSE = 0.22, respectively) and in those without FOG, ON and OFF therapy (r = 0.85 and RMSE = 0.19; r = 0.79 and RMSE = 0.21, respectively). Conclusions: Optimized support vector regression models have high feasibility in predicting PIGD scores in PD. L-Dopa and FOG affect regression model performances. Overall, a single inertial sensor may help to remotely assess axial motor impairment in PD patients.

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.

CSF β-amyloid42 and risk of freezing of gait in early Parkinson disease.

To determine whether CSF biomarkers can be used as a predictor of freezing of gait (FOG) in Parkinson disease (PD) and to investigate the predictive value of clinical, dopamine transporter (DAT) imaging, and CSF parameters both separately and in combination. This study using the PPMI data included 393 patients with newly diagnosed PD without FOG at baseline. We evaluated CSF for β-amyloid 1-42 (Aβ42), α-synuclein, total tau, phosphorylated tau181, and the calculated ratio of Aβ42 to total tau at baseline. Demographic and clinical data and DAT imaging results were also investigated. Cox proportional-hazards regression analyses were performed to identify the factors predictive of FOG. From these results, we constructed a predictive model for the development of FOG. During a median follow-up of 4.0 years, only Aβ42 among the CSF biomarkers was associated with the development of FOG (hazard ratio 0.997, 95% confidence interval [CI] 0.996-0.999, p = 0.009). Postural instability gait difficulty (PIGD) score, caudate DAT uptake, and, to a lesser extent, male sex, Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score, and Montreal Cognitive Assessment score were also predictive of FOG. The combined model integrating the PIGD score, caudate DAT uptake, and CSF Aβ42 achieved a better discriminative ability (area under the curve 0.755, 95% CI 0.700-0.810) than any factor alone. We found CSF Aβ42 to be a predictor of FOG in patients with early PD. Furthermore, the development of FOG within 4 years after diagnosis of PD can be predicted with acceptable accuracy with our risk model.

Subcortical Volumes Differ in Parkinson's Disease Motor Subtypes: New Insights into the Pathophysiology of Disparate Symptoms.

Objectives: Patients with Parkinson’s disease (PD) can be classified, based on their motor symptoms into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry (VBM), however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aimed to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes.Methods: Automated volumetric magnetic resonance imaging (MRI) analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n = 30), in the TD subtype (n = 30), and in 28 healthy controls (HCs).Results: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse) PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better) dual tasking gait speed (r = 0.30, p < 0.002) and with a higher global cognitive score (r = 0.36, p < 0.0001). Lower putamen volume was correlated with a higher (worse) freezing of gait score (r = −0.28, p < 0.004), an episodic symptom which is common among the PIGD subtype. As expected, differences detected between HCs and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD.Conclusions: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions. These findings may, in the future, help to inform a personalized therapeutic approach.

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

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. 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. 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. 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.

Sexual dysfunction is associated with postural instability gait difficulty subtype of Parkinson's disease.

The pathophysiology of the postural instability gait difficulty (PIGD) subtype of Parkinson's disease (PD) is unclear. Information on the spectrum of non-motor symptoms (NMS) in PIGD phenotype is limited. Our objective is to compare the spectrum of NMS in PIGD subtype compared to non-PIGD subgroup in PD patients and to determine predictive factors that are associated with PIGD phenotype. A total of 432 PD patients comprising 158 PIGD and 274 non-PIGD patients were recruited. NMS burden (frequency and severity) was assessed using non-motor symptom scale (NMSS). In the univariable analysis, NMSS total score (P=0.0132), NMSS domain 3 (mood/apathy) score (P=0.0108), NMSS domain 5 (attention/memory) score (P=0.0048) and NMSS domain 8 (sexual function) score (P=0.0052) were significantly higher in the PIGD group than in the non-PIGD group. Using multivariable logistic regression, UPDRS tremor score, UPDRS PIGD score, H&Y staging score and NMSS domain 8 (sexual function) score were found to be significantly different in the PIGD group compared to the non-PIGD group. We disclosed for the first time that PIGD patients demonstrated a greater overall NMS burden and sexual dysfunction and was an independent predictor of PIGD phenotype. Early intervention of sexual dysfunction symptoms in PIGD patients may improve their clinical management.

Local brain activity in different motor subtypes of Parkinson's disease with fMRI

To explore the changes of local brain activity in motor subtypes of Parkinson's disease (PD) with functional magnetic resonance imaging (fMRI). A total of 60 idiopathic PD and 30 age- and gender-matched normal controls were examined with resting-state fMRI from January 2013 to March 2014. All subjects gave their written informed consent for the study. The amplitude of low-frequency fluctuation (ALFF) was calculated to measure local brain activity. The PD patients were divided into two groups of tremor dominant (TD) and postural instability/gait difficulty (PIGD) (n = 30 each). All subjects gave their written in formed consent for the study.One-way ANOVA and post-hoc t-test were performed to detect the differences of local brain activity between PD and normal subjects. And the correlations were examined between ALFF, scores and levodopa dose. Compared with normal subjects, the TD group showed increased activity in bilateral cerebellums (-37, -47, -38), thalamus (-18, -17,0), pons (-3, -23, -37) and left precentral gyrus (-41, -30, 46) versus decreased activity in bilateral frontal lobes (-13, 69, 6), temporal lobes (-42, 18, -21), left insula (-32, 22, 2) and left anterior cingulated (-7, 32, -5). The PIGD group showed increased activity in right postcentral gyrus (63, -18, 39) and decreased activity in bilateral putamens (-24, 12, 3), pre-supplementary motor area (10, 10, 58), frontal lobes (15, -15, 57), temporal lobes (-39, 18, -3) and left insula (-29, 20, 11). Compared with PIGD, the TD group showed increased activity in temporal lobes, but decreased activity in frontal lobes. Additionally, ALFF in bilateral cerebellums and frontal lobes was positively correlated with TD scores while ALFF in left precentral gyrus, bilateral putamens and temporal lobes negatively correlated with TD scores. ALFF in bilateral frontal lobes and left temporal lobe was positively correlated with PIGD scores.However, in right postcentral gyrus and bilateral putamens, ALFF was negatively correlated with PIGD scores. The levodopa dose was positively correlated with frontal lobes and temporal lobe in TD and cerebellums and inferior parietal lobule in PIGD. A specific pattern of intrinsic activity in TD and PIGD may provide insights into neurophysiological mechanisms of PD motor subtypes. The changes of brain activity in TD are caused by the interaction between cerebello-thalamo-cortical circuit and basal ganglia loop while the changes in PIGD result largely from damaged basal ganglia loop.

Cognitive function and other non-motor features in non-demented Parkinson's disease motor subtypes.

Among patients with Parkinson's disease (PD), a wide range of non-motor symptoms (NMS) are evident. We assessed markers of NMS and explored their behavioral correlates with the tremor-dominant (TD) and postural instability gait difficulty (PIGD) subtypes. 110 non-demented patients with PD were evaluated and stratified into the PIGD and TD subtypes and, using stricter criteria, into predominant subgroups: p-PIGD (n = 31) and p-TD (n = 32). Non-motor signs that were assessed included cognitive function (pen and paper and a computerized battery), autonomic function (NMSQest and SCOPA-AUT), mood, and sleep. Health-related quality of life was evaluated using the PDQ-39. The p-PIGD subgroup had a higher score on the NMSQest (p = 0.033) and a higher score (i.e., worse) on the PDQ-39 (p-PIGD: 26.28 ± 12.47; p-TD: 16.93 ± 12.22; p = 0.004), compared to the p-TD subgroup, while these measures did not differ in the larger PIGD and TD group. The p-PIGD subgroup used more sleep medications compared to the p-TD subgroup (1.0 ± 1.39 vs. 0.41 ± 0.94, p = 0.05, respectively). Most cognitive scores were similar in both subgroups; however, the visuospatial components of the Montreal Cognitive Assessment and the computerized catch game were significantly worse among the p-PIGD subgroup. Mild associations were found between certain non-motor symptoms, but not cognitive function, and the PIGD score. Non-demented patients from the PIGD subtype experience more non-motor symptoms and poorer quality of life compared to the TD subtype. These findings suggest that the clinical management of non-motor and motor symptoms in patients with PD may be enhanced by a personalized approach.

Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism.

Drug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent "unmasking" of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed. We performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent. Non-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5-500, p=0.03). A constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease.

Identifying axial and cognitive correlates in patients with Parkinson’s disease motor subtype using the instrumented Timed Up and Go

Parkinson's disease (PD) is clinically highly heterogeneous, often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD). To better understand these subtypes and to help stratify patients, we applied an objective marker, i.e., an instrumented version of the traditional "Timed Up and Go" test (iTUG). It is not known whether the iTUG is sensitive to PD motor phenotypes or what are its behavioral and cognitive correlates. Subjects performed the iTUG wearing a body-fixed sensor. Subcomponents were studied including walking, transitions and turning. Gait, balance and cognitive function and the associations between iTUG, behavioral and cognitive domains were assessed. We also compared two representative subtypes, with minimal symptom overlap, referred to here as predominant PIGD (p-PIGD) and predominant TD (p-TD). One hundred and six patients with PD performed the iTUG. Significant correlations were found between iTUG measures and the PIGD score, but not with TD score. Thirty p-PIGD and 31 p-TD patients were identified. Both groups were similar with respect to age and disease duration (p > 0.75). The p-PIGD patients took significantly longer to complete the iTUG (p = 0.026), used more steps (p = 0.031), albeit with similar step duration (p = 0.936). In the sit-to-stand transition, the p-PIGD patients exhibited lower anterior-posterior jerk (p = 0.04) and lower pitch range (p = 0.012). During the turn, the p-PIGD patients had a lower yaw amplitude (p < 0.038). Cognitive domains were correlated with iTUG measures in the p-PIGD patients, but not in the p-TD. These findings demonstrate that a single sensor can identify axial and cognitive correlates using subcomponents of the iTUG and reveals subtle alterations between the PD motor subtypes.

White Matter Hyperintensities in Parkinson’s Disease: Do They Explain the Disparity between the Postural Instability Gait Difficulty and Tremor Dominant Subtypes?

BackgroundBrain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson’s disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD.Methods110 patients with PD underwent a clinical evaluation and a 3T MRI exam. Based on the Unified Parkinson Disease Rating Scale, the patients were classified into motor sub-types, i.e., TD or PIGD, and scores reflecting PIGD and TD symptoms were computed. We compared white matter burden using three previously validated methods: one using a semi-quantitative visual rating scale in specific brain regions and two automated methods.ResultsOverall, MRI data were obtained in 104 patients. The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes, p = 0.678. The PIGD and the TD scores did not differ even when comparing patients with a relatively high burden of WMHs to patients with a relatively low burden. Across most of the brain regions, mild to moderate correlations between WMHs and age were found (r = 0.23 to 0.41; p<0.021). Conversely, no significant correlations were found between WMHs and the PIGD score or disease duration. In addition, depressive symptoms and cerebro-vascular risk factors were similar among the two subtypes.ConclusionsIn contrast to what has been reported previously among older adults, the present study could not demonstrate any association between WMHs and the PIGD or TD motor sub-types in patients with PD.

Diffusion Tensor Imaging of Vascular Parkinsonism

To investigate the white matter (WM) microstructure using diffusion tensor imaging in patients with vascular parkinsonism (VP) and specific fiber tract involvement with respect to clinical severity. Diffusion measures (fractional anisotropy and mean diffusivity) were calculated from diffusion tensor images of patients with VP and control subjects. We performed global-, voxel-, and tract-based analyses to compare WM microstructural properties between groups.We further correlated findings with Unified Parkinson's Disease Rating Scale scores and modified postural instability gait difficulty (PIGD) scores to identify most relevant tract involvement. Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Twelve patients with VP and 12 age-matched healthy controls without VP. In the VP group, the left thalamus, right frontal subcortical WM, and left anterior limb of the internal capsule had a significantly lower regional fractional anisotropy compared with the control group. The bilateral frontal subcortical WM showed a significantly higher regional mean diffusivity. The diffusion metrics in these regions were significantly correlated with the modified PIGD score part III, and the sum of modified PIGD scores parts II and III. Tract-based analysis showed a group difference in mean fractional anisotropy and mean diffusivity for multiple fiber bundles, but only diffusion measures of fiber tracts from the bilateral frontal lobe that pass through the anterior limb of internal capsule and tracts of the genu of the corpus callosum showed significant correlation with these scores. Disruption of the microstructural organization of frontal lobe WM is associated with the severity of VP. Our findings are in accordance with the frontal lobe disconnection hypothesis for gait problems and reinforce the paradigm that the involvement of fibers related to the prefrontal cortex is crucial for the core features of VP.

Cognitive impairment in Parkinson’s disease

Background:Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use...