Early-stage Parkinson's Disease Research Articles

18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease.

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.

Association of Total Bilirubin with Motor Signs in Early Parkinson's Disease in LRRK2 Variant Carriers.

Oxidative stress is considered a possible mechanism in Parkinson's disease (PD) progression. Bilirubin has been recognized as a powerful antioxidant that increases due to heme-oxygenase activity. We aimed to investigate the association of total bilirubin (TB) with motor signs and asymmetry in different stages of early PD. A case-control study was performed to investigate the differences in TB levels in PD patients and healthy controls (HC) both carrying LRRK2 variants. We compared TB levels in HC and Hoehn and Yahr (HY) I and II cohorts separately, followed by multiple linear regression analysis to evaluate the association between TB and motor dysfunction in each stage. We used Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (UPDRS) part III scores and asymmetry scores to address motor disability. Asymmetry scores were calculated from the corresponding UPDRS III tasks. TB was significantly increased in HY II compared to HC (P < 0.001). Positive correlations with TB were found for UPDRS III total score (ρ = 0.303, P = 0.034) and asymmetry score (ρ = 0.418, P = 0.003) in HY I. Multiple linear regression found a significant relationship between TB and asymmetry scores in HY I (R2 = 0.261, P = 0.037), but no relationship was achieved with UPDRS III total scores. Increased TB serves as an important diagnostic marker in earlier stages of PD. A significant relationship was found between TB and motor asymmetry in HY I patients. According to our findings, bilirubin mainly exhibits its protective effects in HY I population.

Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson's Disease.

Gait disturbance is a prototypical feature of Parkinson’s disease (PD), and the quantification of gait using wearable sensors is promising. This study aimed to identify gait impairment in the early and progressive stages of PD according to the Hoehn and Yahr (H–Y) scale. A total of 138 PD patients and 56 healthy controls (HCs) were included in our research. We collected gait parameters using the JiBuEn gait-analysis system. For spatiotemporal gait parameters and kinematic gait parameters, we observed significant differences in stride length (SL), gait velocity, the variability of SL, heel strike angle, and the range of motion (ROM) of the ankle, knee, and hip joints between HCs and PD patients in H–Y Ⅰ-Ⅱ. The changes worsened with the progression of PD. The differences in the asymmetry index of the SL and ROM of the hip were found between HCs and patients in H–Y Ⅳ. Additionally, these gait parameters were significantly associated with Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Questionnaire-39. This study demonstrated that gait impairment occurs in the early stage of PD and deteriorates with the progression of the disease. The gait parameters mentioned above may help to detect PD earlier and assess the progression of PD.

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats.

Background:Rodent Parkinson’s disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient.Objective:To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact.Method:We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr ≤1.5) exercising in non-contact boxing training for ≥3 months, ≥3x/week. In 4-month-old Pink1 knockout (KO) rats exercising in a progressively-increased treadmill speed regimen, we determined a specific treadmill speed that increased HR to an extent similar in human subjects.Results:After completing aerobic exercise for ∼30 min, PD subjects had increased HR∼35% above baseline (∼63% maximum HR). Motor and cognitive test results indicated the exercising subjects completed the timed up and go (TUG) and trail-making test (TMT-A) in significantly less time versus exercise-naïve PD subjects. In KO and age-matched wild-type (WT) rats, treadmill speeds of 8–10 m/min increased HR up to 25% above baseline (∼67% maximum HR), with no further increases up to 16 m/min. Exercised KO, but not WT, rats showed increased locomotor activity compared to an age-matched exercise-naïve cohort at 5 months old.Conclusion:These proof-of-concept results indicate HR is a cross-species translation parameter to evaluate aerobic exercise impact on specific motor or cognitive functions in human subjects and rat PD models. Moreover, a moderate intensity exercise regimen is within the physical abilities of early-stage PD patients and is therefore applicable for interrogating neurobiological mechanisms in rat PD models.

Adenosine A2A receptor availability in patients with early- and moderate-stage Parkinson’s disease

IntroductionAdenosine 2A (A2A) receptors co-localize with dopamine D2 receptors in striatopallidal medium spiny neurons of the indirect pathway. A2A receptor activation in the striatum or pallidum decreases D2 signaling. In contrast, A2A receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A2A receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A2A receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A2A receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias.MethodsBrain MRI and PET with [11C]TMSX radioligand, targeting A2A receptors, was performed in 9 patients with early- and 9 with moderate-stage PD without dyskinesia and in 6 healthy controls. Distribution volume ratios (DVR) were calculated to assess specific [11C]TMSX binding in caudate, putamen and pallidum.ResultsA2A receptor availability (DVR) was decreased in the bilateral caudate of early-stage PD patients when compared with healthy controls (P = 0.02). Conversely, DVR was increased bilaterally in the pallidum of moderate-stage PD patients compared to healthy controls (P = 0.03). Increased mean striatal DVR correlated with higher motor symptom severity (rho = 0.47, P = 0.02).ConclusionOur results imply regional and disease stage-dependent changes in A2A receptor signaling in PD pathophysiology and in response to dopaminergic medication.

Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease.

Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear. Here it is found that choline acetyltransferase (ChAT)‐positive neurons in the dorsal motor nucleus of the vagus nerve (DMV), are lost in PD transgenic mice. In response to the selective damaging of DMV neurons with mu p75‐SAP, a rapid reduction both in plasma total and active ghrelin levels is observed. While by contrast, chemogenetic activation of DMV cholinergic neurons can increase the plasma ghrelin levels. Impairment of cholinergic neurons is accompanied by GI disorders, including decreased stool wet weight, stool dry weight, small intestine advancing rate, and gastric emptying rate, while exogenous ghrelin treatment can partially ameliorate GI dysfunction of A53T α‐synuclein transgenic mice. Using pseudorabies virus retrograde trace method, the existence of a direct pathway from the stomach fundus to the DMV is shown. Taken together, the findings suggest that the reduction in plasma ghrelin levels in the early stages of PD may be the result of the lesion of cholinergic neurons in the DMV, thus linking neurodegeneration and GI dysfunction in PD.

Combination of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Provides Potential Biomarkers for Early-Stage Parkinson's Disease.

Purpose: This study aimed to detect changes in iron deposition and neural microstructure in the substantia nigra (SN), red nucleus (RN), and basal ganglia of Parkinson's disease (PD) patients at different stages using quantitative susceptibility mapping and diffusion kurtosis imaging to identify potential indicators of early-stage PD. Methods: We enrolled 20 early-stage and 15 late-stage PD patients, as well as 20 age- and sex-matched controls. All participants underwent quantitative susceptibility mapping and diffusion kurtosis imaging to determine magnetic susceptibility (MS), fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) in several brain regions. Results: Compared with the control group, MS and MK values in the SN were significantly increased in the early- and late-stage PD group, whereas MS values in the red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), FA value in the CN and GP, and MK value in the CN and putamen (PU) were significantly increased in the late-stage PD group. There were positive correlations between MS and MK values in the CN and MS and FA values in the GP. Furthermore, the combination of MS and MK values in the SN provided high accuracy for distinguishing early-stage PD patients from controls. Conclusions: This study identified MS and MK in the SN as potential indicators of early-stage PD.

Wearable Sensor-Based Chronic Condition Severity Assessment: An Adversarial Attention-Based Deep Multisource Multitask Learning Approach

Advancing the quality of healthcare for senior citizens with chronic conditions is of great social relevance. To better manage chronic conditions, objective, convenient, and inexpensive wearable sensor- based information systems (IS) have been increasingly used by researchers and practitioners. However, existing models often focus on a single aspect of chronic conditions and are often “black boxes” with limited interpretability. In this research, we adopt the computational design science paradigm and propose a novel adversarial attention-based deep multisource multitask learning (AADMML) framework. Drawing upon deep learning, multitask learning, multisource learning, attention mechanism, and adversarial learning, AADMML addresses limitations with existing wearable sensor-based chronic condition severity assessment methods. Choosing Parkinson’s disease (PD) as our test case because of its prevalence and societal significance, we conduct benchmark experiments to evaluate AADMML against state-of-the-art models on a large-scale dataset containing thousands of instances. We present three case studies to demonstrate the practical utility and economic benefits of AADMML and by applying it to detect early-stage PD. We discuss how our work is related to the IS knowledge base and its practical implications. This work can contribute to improved life quality for senior citizens and advance IS research in mobile health analytics.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12months after thalamotomy. We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Longitudinal corpus callosum microstructural decline in early-stage Parkinson’s disease in association with akinetic-rigid symptom severity

Previous diffusion tensor imaging (DTI) studies of Parkinson’s disease (PD) show reduced microstructural integrity of the corpus callosum (CC) relative to controls, although the characteristics of such callosal degradation remain poorly understood. Here, we utilized a longitudinal approach to identify microstructural decline in the entire volume of the CC and its functional subdivisions over 2 years and related the callosal changes to motor symptoms in early-stage PD. The study sample included 61 PD subjects (N = 61, aged 45–82, 38 M & 23 F, H&Y ≤ 2) from the Parkinson’s Progressive Markers Initiative database (PPMI). Whole-brain voxel-wise results revealed significant fractional anisotropy (FA) and mean diffusivity (MD) changes in the CC, especially in the genu and splenium. Using individually drawn CC regions of interest (ROI), our analysis further revealed that almost all subdivisions of the CC show significant decline in FA to certain extents over the two-year timeframe. Additionally, FA seemed lower in the right hemisphere of the CC at both time-points, and callosal FA decline was associated with FA and MD decline in widespread cortical and subcortical areas. Notably, multiple regression analysis revealed that across-subject akinetic-rigid severity was negatively associated with callosal FA at baseline and 24 months follow-up, and the effect was strongest in the anterior portion of the CC. These results suggest that callosal microstructure alterations in the anterior CC may serve as a viable biomarker for akinetic-rigid symptomology and disease progression, even in early PD.

Correlation of matrix metalloproteinase 3 and matrix metalloproteinase 9 levels with non-motor symptoms in patients with Parkinson's disease.

ObjectiveMatrix metalloproteinases (MMPs) are essential for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. MMPs have been widely studied in acute brain diseases. However, the relationship with Parkinson’s disease (PD) remains unclear. The purpose of this study was to evaluate the serum MMP3 and MMP9 levels of PD patients and analyze their correlation with non-motor symptoms.MethodsIn this cross-sectional study, we recruited 73 patients with idiopathic PD and 64 healthy volunteers. Serum MMP3 and MMP9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with PD were assessed for non-motor symptoms using the Non-motor Symptoms Scale (NMSS) and Parkinson’s disease sleep scale (PDSS) and Mini Mental State Examination (MMSE).ResultsSerum MMP3 levels were significantly decreased in PD patients, predominantly those with early-stage PD, compared with controls [12.56 (9.30, 17.44) vs. 15.37 (11.33, 24.41) ng/ml; P = 0.004], and the serum MMP9 levels of PD patients were significantly higher than those of healthy controls [522 (419, 729) vs. 329 (229, 473) ng/ml; P < 0.001]. MMP3 levels were positively correlated with the NMSS total score (r = 0.271, P = 0.020) and the single-item scores for item six, assessing the gastrointestinal tract (r = 0.333, P = 0.004), and there was an inverse correlation between serum MMP3 levels and PDSS score (r = –0.246, P = 0.036); meanwhile, MMP9 levels were positively correlated with the NMSS total score (r = 0.234, P = 0.047), and higher serum MMP9 levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [658 (504, 877) vs. 502 (397, 608) ng/ml, P = 0.008].ConclusionThe serum MMP3 level of PD patients (especially early-stage patients) was significantly lower than that of the healthy control group, and the MMP9 level was significantly higher than that of the healthy control group. MMP3 and MMP9 levels correlate with sleep disturbance and cognitive function in PD patients, respectively.

Classification of Parkinson’s disease and its stages using machine learning

As digital health technology becomes more pervasive, machine learning (ML) provides a robust way to analyze and interpret the myriad of collected features. The purpose of this preliminary work was to use ML classification to assess the benefits and relevance of neurocognitive features both tablet-based assessments and self-reported metrics, as they relate to Parkinson’s Disease (PD) and its stages [Hoehn and Yahr (H&Y) Stages 1–5]. Further, this work aims to compare perceived versus sensor-based neurocognitive abilities. In this study, 75 participants (n = 50 PD; n = 25 control) completed 14 tablet-based neurocognitive functional tests (e.g., motor, memory, speech, executive, and multifunction), functional movement assessments (e.g., Berg Balance Scale), and standardized health questionnaires (e.g., PDQ-39). Decision tree classification of sensor-based features allowed for the discrimination of PD from healthy controls with an accuracy of 92.6%, and early and advanced stages of PD with an accuracy of 73.7%; compared to the current gold standard tools [e.g., standardized health questionnaires (78.3% accuracy) and functional movement assessments (70% accuracy)]. Significant features were also identified using decision tree classification. Device magnitude of acceleration was significant in 12 of 14 tests (85.7%), regardless of test type. For classification between diagnosed and control populations, 17 motor (e.g., device magnitude of acceleration), 9 accuracy (e.g., number of correct/incorrect interactions), and 8 timing features (e.g., time to between interactions) were significant. For classification between early (H&Y Stages 1 and 2) and advanced (H&Y Stages 3, 4, and 5) stages of PD, 7 motor, 12 accuracy, and 14 timing features were significant. Finally, this work depicts that perceived functionality of individuals with PD differed from sensor-based functionalities. In early-stage PD was shown to be 21.6% lower than sensor-based scores with notable perceived deficits in memory and executive function. However, individuals in advanced stages had elevated perceptions (1.57x) for executive and behavioral functions compared to early-stage populations. Machine learning in digital health systems allows for a more comprehensive understanding of neurodegenerative diseases and their stages and may also depict new features that influence the ways digital health technology should be configured.

Comparison of 18 F-DOPA and 18 F-DTBZ for PET/CT Imaging of Idiopathic Parkinson Disease.

The aim of this study was to compare 2 imaging tracers, 18 F-DOPA and 18 F-DTBZ, for PET/CT imaging in idiopathic Parkinson disease (PD). We recruited 32 PD patients and 12 healthy controls in this study. All subjects underwent both 18 F-DOPA and 18 F-DTBZ PET/CT, and the results were interpreted by visual analysis and semiquantitative analysis (specific uptake ratios [SURs]). A 1-way analysis of variance was used to compare the clinical data and the SURs among the patients at different stages. Regression analysis was performed to analyze the correlation between the SURs and the clinical data. Among the PD patients, there were 7 patients in Hoehn and Yahr stage I, 14 patients in stage II, and 11 patients in stage III. Linear correlation was found in striatal SURs between the 2 tracers ( P < 0.05). In patients of early stages, the striatal SUR decrease percent of 2 tracers had no statistical difference (paired t test, P > 0.05). By initial visual analysis, all the patients were interpreted as positive with 18 F-DBTZ (6 unilaterally, 26 bilaterally), and 31 cases were regarded as positive with 18 F-DOPA (8 unilaterally, 23 bilaterally). After setting the upper limit of SUR images with the putamen SURs of healthy controls (SUR T ), all patients were interpreted as positive with both tracers ( 18 F-DTBZ: 5 unilaterally, 27 bilaterally; 18 F-DOPA: 4 unilaterally, 28 bilaterally). 18 F-DTBZ and 18 F-DOPA could reflect the same level of dopaminergic neuron degeneration for PD in early stages, and they have the consistent visual analysis results.

Brain Metabolic Correlates of Dopaminergic Denervation in Prodromal and Early Parkinson's Disease.

It remains unclear how brain metabolic activities transform in response to dopamine deficiency in the prodromal and early phases of Parkinson's disease (PD). To investigate the relationship between nigrostriatal dopaminergic denervation and brain glucose metabolism in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and early PD. This cohort study included 28 patients with polysomnography-confirmed iRBD, 24 patients with de novo PD with probable rapid eye movement sleep behavior disorder (denovo PD), and 28 healthy controls (HCs) who underwent two positron emission tomography scans with 18 F-fluorodeoxyglucose (all participants) and 18 F-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (except for one denovo PD patient and 15 HCs). We analyzed striatal and voxel-wise whole-brain glucose metabolism in relation to nigrostriatal dopaminergic integrity and comparatively investigated the whole-brain metabolic connectivity among the groups. We also assessed longitudinal metabolic changes against progressive dopaminergic denervation over 4 years in the iRBD group. From HCs to iRBD and finally to the denovo PD, dopaminergic integrity positively correlated with metabolic activity in the caudate, whereas a negative correlation was observed in the posterior putamen. In the iRBD group, there was a metabolic increase in the inferior orbitofrontal cortex against putaminal dopaminergic denervation at baseline, but negative correlations were newly observed in the superior orbitofrontal cortex and superior frontal gyrus at the 4-year follow-up. The denovo PD group showed negative correlations in the cerebellum and fusiform gyrus. Intra- and inter-regional metabolic connectivities in the parieto-occipital cortices were enhanced in the iRBD group compared with the denovo PD and HC groups. In the iRBD group, overall metabolic connectivity was strengthened along with enhanced basal ganglia-frontal connection by advancing dopaminergic denervation. Our findings suggest diverse trajectories of metabolic responses associated with dopaminergic denervation between individual brain areas in the prodromal and early PD stages. © 2022 International Parkinson and Movement Disorder Society.

Neurocognitive functioning of patients with early-stage Parkinson’s disease

Parkinson’s disease (PD) is a neurological disorder commonly associated with motor deficits. However, cognitive impairment is also common in patients with PD. Cognitive concerns in PD may affect multiple domains of neurocognition and vary across different stages of the disease. Extant research has focused mainly on cognitive deficits in middle to late stages of PD, whereas few studies have examined the unique cognitive profiles of patients with early-stage PD. This study addressed this gap in the published literature and examined neurocognitive functioning and functional capacity of patients with de novo PD, focusing on the unique pattern of cognitive deficits specific to the early stage of the disease. Results indicated that the pattern of cognitive deficits in patients with PD (n = 55; mean age = 72.93) was significantly different from healthy controls (n = 59; mean age = 71.88). Specifically, tasks related to executive functioning, attention, and verbal memory demonstrated the most pronounced deficits in patients with early-stage PD. Clinical implications of these findings are discussed.

Role of the gut-microbiota-metabolite axis in the rotenone model of early-stage Parkinson's Disease.

Gastrointestinal symptoms are common in the early-stage Parkinson's disease (PD), but its potential pathogenesis remains unclear. Therefore, in the present study, we used the 16S ribosomal RNA gene sequencing and gas chromatography coupled with mass spectrometry-based metabolomics to investigate the alterations of gut microbiome and serum amino acid levels in the early-stage PD mice model induced with rotenone. The results demonstrated that the microbial taxa at phylum, family and genus levels remarkably altered in rotenone-induced mice relative to vehicle-induced mice. The rotenone-induced mice had higher relative abundance of Flavobacteriaceae, Staphylococcaceae, and Prevotellaceae as well as lower relative abundance of Lachnospiraceae_UCG-001, Ruminiclostridium, and Prevotellaceae_NK3B31_group than vehicle-induced mice. The evaluation of serum amino acids revealed the alterations in several classes of amino acids, including L-proline, L-alanine, L-serine, L-asparagine, L-threonine, L-glutamine, L-methionine, and L-4-hydroxyproline. Notably, the altered serum amino acid levels were significantly associated with the abundance of gut microbiota, especially Ruminococcaceae and Ruminiclostridium. Our study explored the possible role of the gut-microbiota-metabolite axis in the early-stage PD and provided the possibility of prevention and treatment of PD by gut-microbiota-metabolite axis in the future.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson’s disease

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson’s disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test–retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society–Unified Parkinson's Disease Rating Scale items (rho: 0.12–0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Occupational Therapy for People with Early Parkinson's Disease: A Retrospective Program Evaluation.

Purpose Clinical practice guidelines establish that occupational therapy (OT) services are indicated for people with early Parkinson's disease (PD). However, OT is uncommon compared to other rehabilitation services. This study describes the development and evaluation of a proactive, consultative OT program for people with early PD as a part of an integrated care approach. Materials and Methods The program was developed by an occupational therapist adapting practice guidelines for people with early PD. Retrospective program evaluation occurred at an outpatient rehabilitation clinic. The consultative OT program for early PD includes a 90-minute evaluation with instruction in self-management techniques, individually tailored exercises, and follow-up recommendations. The program was evaluated with the RE-AIM framework. Postprogram semistructured interviews provided patient-reported program effectiveness and satisfaction. Results In 2018, 23 individuals used OT out of 77 people with early PD who attended the proactive rehabilitation program. Most individuals (n = 16, 69.6%) were within Hoehn and Yahr stages 1-2 and were seen within 3 years of PD diagnosis. Participants presented with deficits in hand strength (60.0 ± 23.4 pounds) and dexterity (right hand 30.0 ± 8.0 seconds) and reported complaints about basic and/or instrumental activities of daily living (n = 15, 65.2%). Semistructured interviews (n = 16) revealed that most individuals (75%) reported high satisfaction. Of the 10 who recalled a home exercise program, 60% reported continued adherence. Consultative OT was delivered with fidelity in 22/23 individuals (96%). After one year, only two occupational therapists at one clinic had adopted the program, and the program is maintained in the organization. Conclusion Occupational therapists reached people in the early stages of PD when a specific program was tailored to evaluate and target their specific needs. Motor activity deficits noted in individuals with early PD support future scaling and sustainability efforts of OT within this population. Quality improvement suggestions are discussed for future implementation and clinical trials.

Characterization of Early Stage Parkinson's Disease From Resting-State fMRI Data Using a Long Short-Term Memory Network.

Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.

Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.