Hoehn-Yahr Research Articles

High-Frequency Repetitive Magnetic Stimulation at the Sacrum Alleviates Chronic Constipation in Parkinson's Patients.

This study was to investigate the therapeutic effect of high-frequency repetitive magnetic stimulation (HF-rMS) at the sacrum for chronic constipation in Parkinson's patients (PD). Eventually 48 PD patients were enrolled from July 2019 to October 2020, and randomly divided into the HF-rMS group (the intervention group, n = 24) and the sham HF-rMS group (the control group, n = 24). The intervention group received HF-rMS at the sacrum, whereas the control group received ineffective magnetic stimulation. We performed clinical evaluation before and after HF-rMS treatment, including constipation score scale (KESS questionnaire), Unified Parkinson's Disease Rating Scale (UPDRS-III exercise examination), Hoehn-Yahr (H-Y) stage of motor function; simple mental status scale (MMSE), anxiety/depression table (HAD-A/HAD-D), the activity of daily living (ADL), and quality of life scale for patients with constipation (PAC-QOL) to evaluate symptoms and satisfaction of PD patients with chronic constipation. There was no significant difference in the clinical characteristics between the two groups. As compared to the control group, the HF-rMS group displayed a larger change (pre and posttreatment) in the KESS scores of PD patients with chronic constipation, suggesting a significant improvement. Moreover, HF-rMS significantly promoted the mood, activity of daily living, and quality of life of PD patients when comparing the alteration of HAD-A/HAD-D scores, ADL scores, and PAC-QOL scores between the two groups. Finally, there was no significant difference in the change of the UPDRS III score and the MMSE score between the two groups. HF-rMS at the sacrum can improve chronic constipation in PD patients.

Serum levels of p-tau181 in patients with Parkinson’s disease

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease. Evidence has shown that phosphorylated tau-181 (p-tau181) is involved in the pathological process of PD. The goal of this study was to investigate the changes of serum phosphorylated Microtubule-associated protein tau at threonine-181 in patients with Parkinson's disease and it's correlation with disease severity, cognitive impairment and prognosis. Methods: A total of 40 patients with primary Parkinson's disease who were hospitalized or outpatient in the First Affiliated Hospital of Chongqing Medical University from July 2021 to February 2022 were selected as the study subjects. Patients with secondary Parkinson's disease, Parkinson's syndrome, stroke, Alzheimer's disease, craniocerebral surgery or trauma, severe systemic or infectious diseases, local or systemic infectious diseases, motor neurone disease or other central nervous system diseases were excluded. In addition, 35 healthy subjects with similar age and gender matching were selected as the healthy control group. Age, gender, course of disease, Hoehn-Yahr (H-Y) scale, Unified Parkinson's Disease Scale (UPDRS), and MoCA score were recorded in the Parkinson's disease group. According to the H-Y scale, PD group was divided into PD patients in the advanced stage (H-Y≤2.5, n=16) and PD patients in the advanced stage (H-Y>2.5, n=24). Six months after blood sample collection, we assessed the H-Y rating and UPDRS score in the Parkinson's group again by telephone follow-up. Those with decreased or unchanged H-Y rating or total UPDRS score were divided into good prognosis group (n=25), and those with increased H-Y rating or total UPDRS score were divided into poor prognosis group (n=14). The serum p-tau181 concentration of all subjects was detected and compared by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the correlation between serum p-tau181 level and UPDRS score, MoCA score and prognosis of Parkinson's disease patients was analyzed. Results: Compared with HC, serum p-tau181 concentration in PD patients were higher, but not statistically significant (1.01[0.28-2.63]vs 0.53[0.04-3.72]ug/mL, P=0.55, P>0.05). There was no significant difference in p-tau181 concentration between PD patients in early stage and PD patients in advanced stage (P=0.80 P>0.05), and no significant difference in p-tau181 level between PD patients with cognitive impairment, PD patients with normal cognition and HC patients (P=0.63, p>0.05). P-tau181 was not significantly correlated with disease duration (r=-0.14, P=0.37, P>0.05), UPDRS score (r=0.02, P=0.89, P>0.05), and MoCA score (r= 0.16, P=0.32, P > 0.05). There was no significant difference in serum P-tau181 expression between good prognosis group and poor prognosis group (P=0.74, P > 0.05). Conclusions: Serum expression of p-tau181 increased in PD patients, but no statistical difference was observed, and no clear correlation was found between p-tau181 and disease severity and cognitive impairment. Serum p-tau181 level in PD patients has no significant prognostic significance.

Deep brain stimulation improves central nervous system inflammation in Parkinson's disease: Evidence and perspectives.

In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD. We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed. RANTES (p < 0.001) and TNF-α (p=0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs =0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1 =0.644, p=0.033 and rs2 =0.620, p=0.042) were observed in matched patients. No correlation was observed for TNF-α levels. The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

The Relationship between Visual-Evoked Potential and Optic Coherence Tomography and Clinical Findings in Parkinson Patients.

In Parkinson's disease (PD), dopamine deficiency is present not only in the nigrostriatal pathway but also in the retinal and visual pathways. Optic coherence tomography (OCT) can be used as morphological evidence of visual influence from early nonmotor symptoms. The aim of this study was to investigate the relationship of OCT and visual evoked potentials (VEPs) of eyes with the severity of clinical findings and ocular findings in PD. A group of 42 patients diagnosed with idiopathic PD and a control group of 29 people between the ages of 45-85 were included in our study. VEP was recorded in the patient and control groups. OCT measurement was made with the Optovue spectral-domain device. Foveal thickness and macular volume were measured in the foveal region and in the parafoveal and perifoveal regions in the temporal, superior, nasal, and inferior quadrants. RNFL (retinal nerve fiber layer) was measured in temporal, superior, nasal, and inferior quadrants. Ganglion cell complex (GCC) was evaluated in the superior and inferior quadrants. Using the UPDRS clinical scale, the relationship between measurements and the differences between the control group and the patient group were evaluated. Among the OCT values in our study, foveal, parafoveal, perifoveal thickness, macular volume, RNFL, and GCC measurements were performed for the right and left eyes, and no difference was found between the patient group and the control group. There was no difference in VEP amplitude and latency values between the patient and control groups. The relationships between UPDRS and modified Hoehn Yahr staging and OCT and VEP measurements in the patient revealed no correlation. Studies on whether OCT measurements can functionally be a marker or which segments are more valuable for disease progression in patients with PD are needed. Visual dysfunction in PD cannot be attributed only to retinal pathology; however, the retina may provide monitoring of the status of dopaminergic neurodegeneration and axonal loss in PD.

Using of MRI-guided focused ultrasound treatment for Parkinson’s disease tremor. Clinical case and literature review

MRI-guided high-intensity focused ultrasound (MRgFUS) is a new emerging and promising procedure applied in a wide range of clinical fi elds in modern medicine. This innovative treatment method follows is an important step towards the ideal surgery of the future: non-invasive, targeted, safe, controlled, eff ective and ambulatory. Randomized studies show high effi cacy in the treatment of tremor for Parkinson disease and essential tremor. Safety is also having similar profi le with other surgical procedures and has a mostly transient character of complications. Such advantages as a non-invasive treatment, controlled eff ect and the safety profi le of the procedure made it popular in the treatment of movement disorders. This article demonstrates a clinical case of the fi rst using of MRgFUS for the treatment of Parkinson’s disease tremor at the Federal Center for Brain Research and Neurotechnologies of the Federal Medical and Biological Agency of Russia in Moscow. The 54-year-old patient with Parkinson disease, 2 Hoehn–Yahr, admitted to our hospital. Severe tremor of right upper extremity impaired his life. Neurosurgical procedure was considered due to medication failed. Patient underwent focused ultrasound thalamotomy with totally tremor relief. No additional neurological impairment was noted, only bradykinesia and rigidity were improved. Patient discharged on 3rd day after the procedure.Conclusions. MRgFUS is an innovative surgical procedure. Advantages of these methods such as non-invasive manner, controlled, safety allowed to be priority procedure for patients with unilateral tremor.

Application value of multiparametric MRI for evaluating iron deposition in the substantia nigra in Parkinson's disease.

This study aimed to investigate the application value of multi-parametric magnetic resonance imaging (MRI) in the diagnosis of iron deposition in the substantia nigra dense zone in Parkinson's disease (PD) and to evaluate the diagnostic value of the correlation among multi-parametric imaging indicators, clinical stage, and disease duration. Thirty-six patients with clinically confirmed PD and 36 healthy controls were enrolled. The disease course was recorded, and PD severity was graded using the Hoehn-Yahr (H-Y) scale. All subjects underwent magnetic sensitivity weighted imaging (SWI), neuromelanin magnetic resonance imaging (NM-MRI), and a T2*mapping sequence. Based on the fusion of the NM-MRI and SWI amplitude maps, phase maps, and T2*MAPPING value maps, NM-MRI was used to delineate the dense zone of the substantia nigra, which was divided into three sub-regions: upper, middle, and lower. In this way, the amplitude, phase, and R2* values of each sub-region and the average value of the sum of the three sub-regions were obtained simultaneously in the SWI amplitude, phase, and T2*MAPPING maps. The multi-parameter imaging indices were compared between the two groups, and the correlation between them and clinical indices was evaluated in the PD group. The upper (amplitude, phase value, R2* value), middle, and lower (amplitude) right substantia nigra compact zones were significantly different between the PD and control groups. The upper (phase value, R2* value) and middle (amplitude) areas of the left substantia nigra compact zone were also significantly different between the two groups (all P < 0.05). The mean values (amplitude, phase value, R2* value) of the right substantia nigra densification zone and the mean values (phase value) of the left substantia nigra densification zone were also significantly different (all P < 0.05). Amplitudes in the middle and lower parts of the right substantia nigra dense zone were negatively correlated with the H-Y grade (middle: r = -0.475, P = 0.003; lower: r = -0.331, P = 0.049). Amplitudes of the middle and lower parts of the dense zone of the left substantia nigra were negatively correlated with the H-Y grade (middle: r = -0.342, P = 0.041; lower: r = -0.399, P = 0.016). The average amplitude of the right substantia nigra compact zone was negatively correlated with the H-Y grade (r = -0.367, P = 0.027). The average R2* value of the compact zone of the left substantia nigra was positively correlated with the H-Y grade (r = 0.345, P = 0.040). Multiparametric MRI sequence examination has application value in the evaluation of iron deposition in the dense zone of the substantia nigra in PD. Combined with NM-MRI, fusion analysis is beneficial for accurately locating the substantia nigra compact zone and quantitatively analyzing the iron deposition in different sub-regions. Quantitative iron deposition in the middle and lower parts of the substantia nigra dense zone may become an imaging biological indicator for early diagnosis, severity evaluation, and follow-up evaluation of PD and is thus conducive for clinical diagnosis and treatment evaluation.

Clinical significance of serum lncRNA H19, GAS5, HAR1B and linc01783 levels in Parkinson's disease.

<p>Long noncoding RNAs (lncRNAs) are highly expressed in the brain and alterations in their levels have been shown in many neurodegenerative disorders. Evidence has shown that lncRNAs play role in the onset and progression of Parkinson&rsquo;s disease (PD) and it can be used as a potential therapeutic target. Our purpose was to detect whether the serum levels of four candidate lncRNAs H19, GAS5, HAR1B and LINC01783 are related with the clinical findings and treatment of PD or not.&nbsp;</p>. <p>83 patients and 50 healthy controls were included in this study. We assessed how severe the disease is, by using Hoehn Yahr (HY) staging and Unified PD rating scale (UPDRS). Venous blood samples were taken from the participants. Serum samples were centrifuged and stored at -80&deg;C until analysis. Expression levels of these lncRNAs were analyzed by a real-time PCR instrument after RNA isolation and complementary DNA synthesis in the laboratory.</p>. <p>There was no significant difference between PD patients and healthy controls in these lncRNAs&rsquo; serum levels. Just as sociodemographic characteristics, also onset type and right or left predominance of the disease, its duration and treatment did not differ in lncRNA levels. Solely, there was a significant negative correlation between GAS5 and HY and UPDRS scores. Patients with family history of PD had significantly higher levels of LINC01783.</p>. <p>Serum lncRNA GAS5 level may be a possible biomarker for disease severity in PD patients.&nbsp;</p>.

Peripheral Inflammatory Markers TNF-α and CCL2 Revisited: Association with Parkinson’s Disease Severity

One of the major mediators of neuroinflammation in PD is tumour necrosis factor alpha (TNF-α), which, similar to other cytokines, is produced by activated microglia and astrocytes. Although TNF-α can be neuroprotective in the brain, long-term neuroinflammation and TNF release can be harmful, having a neurotoxic role that leads to death of oligodendrocytes, astrocytes, and neurons and, therefore, is associated with neurodegeneration. Apart from cytokines, a wide family of molecules with homologous structures, namely chemokines, play a key role in neuro-inflammation by drawing cytotoxic T-lymphocytes and activating microglia. The objective of the current study was to examine the levels of the serum TNF-α and CCL2 (Chemokine (C-C motif) ligand 2), also known as MCP-1 (Monocyte Chemoattractant Protein-1), in PD patients compared with healthy controls. We also investigated the associations between the serum levels of these two inflammatory mediators and a number of clinical symptoms, in particular, disease severity and cognition. Such an assessment may point to their prognostic value and provide some treatment hints. PD patients with advanced stage on the Hoehn-Yahr scale showed an increase in TNF-α levels compared with PD patients with stages 1 and 2 (p = 0.01). Additionally, the UPDRS score was significantly associated with TNF-α levels. CCL2 levels, however, showed no significant associations.

Persistent intolerable abdominal pain in patients with Parkinson’s disease

ObjectivesIn Parkinson’s disease (PD), pain is common, increases motor disability, and makes daily life unpleasant. Few patients reportedly have a low prevalence of abdominal pain. The pathophysiology of such abdominal pain has not been confirmed. We clinically studied patients with PD and persistent intolerable abdominal pain to determine the pathophysiology and effective therapy. Materials and MethodsWe obtained detailed clinical information from medical records, including the disease course before and after the onset of abdominal pain. The maximal thickness of the rectus muscle at the L4 and L5 corpus vertebral level of the abdomen on axial computed tomography was calculated, and the relative muscle thickness ratio was calculated by dividing the maximal thickness by the distance from the fascia between the bilateral rectus muscles of the abdomen and the dorsal part of the corpus vertebrae. ResultsIn six patients with PD (three men, age range 71–85 years), the Hoehn–Yahr stage, disease duration, and daily levodopa equivalent dose were 3.1 ± 0.7, 107 ± 44 months, and 636.7 ± 451.4 mg/day, respectively. The pain occurred daily and often during the night and was not related to the timing of food intake. The pain in two patients was related to wearing-off. One patient showed constant hypertonic activity in the rectus abdominis on surface electromyography. The rectus abdominis showed that the maximal thickness and relative muscle thickness ratio of patients with abdominal pain were significantly higher than those of patients without pain. Therapeutic usefulness of antiparkinsonian medications was short and limited. ConclusionsAlthough intolerable abdominal pain is likely to be infrequent, it alleviates the quality of life of patients with PD. The pathophysiology seems to vary, and our observations found wearing-off of related pain and muscle contraction, suggesting dystonia. Among persistent abdominal pain, organic abnormalities, such as the precursor state of megacolon, may be lurking.

Association between prediabetes and cognitive function in Parkinson's disease.

It remains largely unknown whether prediabetes is related to cognitive impairment in Parkinson's disease (PD). This study aimed to assess the association between prediabetes and cognitive function in PD patients. In this cross-sectional study, 262 PD patients (age, 69.8±10.3 years; Hoehn-Yahr stage, 2.3±0.8) were classified into diabetes (glycated hemoglobin [HbA1c] ≥6.5% or previously diagnosed, n=76), prediabetes (5.7%-6.4%, n=90), or diabetes free (≤5.6%, n=96) groups. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. Both the diabetes and prediabetes groups had significantly lower MoCA scores (17.0±6.6 and 18.0±6.1, respectively) than the diabetes free group (20.0±5.7), even after adjusting for potential confounders (p=.002 and p=.008, respectively). In the combined group of prediabetes and diabetes free patients, higher HbA1c levels significantly correlated with lower MoCA scores (p=.031). There was a significant interaction of diabetes status with age, but not with the duration of PD, on cognitive function. In addition to diabetes, prediabetes may negatively affect cognitive function in PD patients. Further prospective longitudinal studies are necessary to clarify the impact of prediabetes on the cognitive trajectory of these patients.

Electroconvulsive therapy improves psychotic symptoms in patients with dementia with Lewy bodies.

The aim of this study was to examine the efficacy and safety of electroconvulsive therapy (ECT) for psychotic symptoms of dementia with Lewy bodies (DLB), and also to determine its use as an adaptive criterion. Eight patients aged 66-83years old (mean 75.4±5.9years) diagnosed with probable DLB based on the criteria for DLB and who received ECT between September 2013 and December 2019 at Aichi Medical University were enrolled. The efficacy and safety of ECT were retrospectively examined. Psychotic symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS), while parkinsonism was evaluated based on Hoehn-Yahr (HY) stage, with both scores analyzed and comparedstatistically between before and after ECT. Additionally, a follow-up survey after undergoing ECT was performed. Two incidents occurred during ECT sessions, arrhythmia in one patient and respiratory arrest in another, both of whom quickly recovered. Following ECT, a significant improvement in BPRS score was noted (p<0.018, Wilcoxon signed rank test), whereas no significant difference was seen in regard to HY stage (p=0.059). Follow-up survey findings obtained after ECT (mean observation period 15.9±16.7months), showed that all eight patients were alive and none had a relapse of psychotic symptoms. The present results suggest that ECT for patients with mild to moderate DLB and drug therapy-resistant psychotic symptoms is safe, well tolerated and effective. We consider it worth considering as a DLB therapeutic option.

People with mild Parkinson's disease have impaired force production in upper limb muscles: A cross-sectional study.

There has been little examination of force production of the upper limb in people with Parkinson's disease (PD), despite its impact on activities of daily living and clear evidence that force production is significantly reduced in lower limb muscle groups. The aim of this study was to determine the force production of the major muscle groups of the upper limb in people with PD during the "on" phase after medication, compared with aged-matched neurologically-normal controls. A cross-sectional study was carried out. Thirty people with mild PD (Hoehn Yahr mean 1.1) and 24 age-matched neurologically-normal controls. Maximum isometric force production of the shoulder flexors, extensors, abductors, adductors, internal rotators and external rotators, elbow flexors and extensors, wrist flexors and extensors and hand grip using dynamometry. There was a significant impairment in force production in all upper limb muscle groups, compared with control participants, except in the wrist flexors. On average the deficit in force production was 22%, despite people with PD having mild disease, being physically active and being measured during the "on" phase of medication. The most severely affected muscle groups were the upper limb extensors. People with PD have a significant deficit in force production of the upper limb muscle groups compared with age-matched neurologically normal controls. Regular assessment of strength of the upper limb should be considered by clinicians and strengthening interventions could be implemented if a deficit is identified.

Assessment of progression of Parkinson’s disease using magnetic resonance morphometry

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world, however, structural changes in the brain at different stages and the associated pathophysiological mechanisms remain unclear.Objective: to study MR-morphometric changes in the cerebral cortex in the early and advanced stages of PD in comparison with the control group.Material and methods. 88 patients with PD were examined (II stage of the disease — 42 people, III stage — 46 people according to the Hoehn–Yahr scale). The control group consisted of 35 people who did not differ in sex and age with initial manifestations of cerebrovascular insufficiency. All groups included in the study underwent a neurological examination, as well as magnetic resonance imaging of the brain on a Philips Achieva 3.0T apparatus, followed by post-processing processing of the T1 gradient echo images obtained using FreeSurfer 6.0 software.Results. In patients with stage II PD, compared with the control group, a significant decrease in the thickness of the cortex was found in the gyrus of the precuneus (p = 0.014) of the lateral part of the superior temporal gyrus, inferior frontal gyrus, postcentral sulcus, superior temporal sulcus, which progressed during the transition to the third the stage of the disease and can serve as a marker of the progression of the neurodegenerative process.Conclusion. A morphometric study of the cerebral cortex in PD makes it possible to clarify some links in the pathogenesis of the formation, including dopamine-independent symptoms of the disease.

Soluble LRP-1 in Parkinson’s disease: clues for paradoxical effects

Background: Low density lipoprotein receptor-related protein-1 (LRP-1) is highly expressed in the central nervous system and plays a role in neurodegenerative disorders. The available data on this subject-matter seem to support the presence of a correlation between LRP-1 levels and abnormal aggregation of a plurality of proteins, including tau, amyloid, and α‑synuclein. Understanding the molecular mechanisms underlying Parkinson’s disease (PD) is critical for development of new therapies. Aim: To investigate serum soluble LRP-1 (sLRP-1) concentrations in patients with PD and explored their potential role as a biomarker in diagnosis and prognosis of disease. Methods: Based on well-defined inclusion and exclusion criteria, we have included 133 PD patients and 45 healthy controls. The clinical severity was assessed using Hoehn Yahr and Unified PD Rating Scale (UPDRS). Following a fasting period, venous blood samples were taken, and centrifuged. Serum samples were stored until analysis. sLRP-1 was measured by ELISA assay. Results: The median of serum sLRP-1 levels was higher in PD patients compared to that in healthy controls, but without reaching a statistical significance. There was a positive, but statistically insignificant, correlation between sLRP-1 levels and duration of disease. sLRP-1 levels had a significant correlation with UPDRS Parts I and IV. Patients with hypertension showed lower levels of sLRP-1. Conclusion: The present study suggests that serum sLRP-1 concentrations are associated with the factors influencing prognosis of PD and disease severity. Further studies are needed to definitively determine whether or not sLRP-1 can be utilized as a diagnostic and prognostic biomarker for 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.

Neuroprotective Effects of Intermittent Theta Burst Stimulation in Parkinson's Disease (NET-PD): A Study Protocol for a Delayed-Start Randomized Double-Blind Sham-Controlled Trial.

Background: As a typical high-disability neurodegenerative disease, Parkinson’s disease (PD) progresses variably, and patients who are clinically insensitive to dopaminergic therapy and whose symptoms fail to improve are commonly observed. As a result, achieving early neuron protection is critical. Methods/Design: The NET-PD study is a 2-year prospective single-center, double-blind, multi-arm, delayed-start, sham-controlled clinical trial assessing the long-term neuroprotective effect of intermittent theta burst stimulation (iTBS) in PD patients. Patients diagnosed with PD, aged 50–80, Hoehn–Yahr stage ≤4, and who maintain medication stability during the study will be enrolled. Clinical assessment and multi-modal markers are used to clarify the clinical improvement and dynamic neuronal changes in PD patients. With a standard deviation of 2, a test level of 0.05, a dropout rate of 10%, and a degree of certainty of 0.9, 60 PD patients are required for this study. Results: The NET-PD project was funded in March 2022, data collection began in July 2022, and is currently in the recruitment phase with two PD patients already enrolled. Data collection is expected to be completed in June 2024. The results are expected for publication in December 2024. Discussion: Previous research has demonstrated a rudimentary method for assessing and delaying PD progression in clinical medication trials. The NET-PD study adopts a rigorous methodology and specific disease-modifying designs to demonstrate the neuroprotective effect of iTBS on PD and investigate the potential mechanism of iTBS in regulating brain and motor functions. We hope to provide supposition for the subsequent exploration of diverse neuroprotection methods.

Modulation of cortical resting state functional connectivity during a visuospatial attention task in Parkinson's disease.

Visual dysfunction is a recognized early symptom of Parkinson's disease (PD) that partly scales motor symptoms, yet its background is heterogeneous. With additional deficits in visuospatial attention, the two systems are hard to disentangle and it is not known whether impaired functional connectivity in the visual cortex is translative in nature or disrupted attentional modulation also contributes. In this study, we investigate functional connectivity modulation during a visuospatial attention task in patients with PD. In total, 15 PD and 16 age-matched healthy controls performed a visuospatial attention task while undergoing fMRI, in addition to a resting-state fMRI scan. Tensorial independent component analysis was used to investigate task-related network activity patterns. Independently, an atlas-based connectivity modulation analysis was performed using the task potency method. Spearman's rank correlation was calculated between task-related network expression, connectivity modulation, and clinical characteristics. Task-related networks including mostly visual, parietal, and prefrontal cortices were expressed to a significantly lesser degree in patients with PD (p < 0.027). Resting-state functional connectivity did not differ between the healthy and diseased cohorts. Connectivity between the precuneus and ventromedial prefrontal cortex was modulated to a higher degree in patients with PD (p < 0.004), while connections between the posterior parietal cortex and primary visual cortex, and also the superior frontal gyrus and opercular cortex were modulated to a lesser degree (p < 0.001 and p < 0.011). Task-related network expression and superior frontal gyrus–opercular cortex connectivity modulation were significantly associated with UPDRSIII motor scores and the Hoehn–Yahr stages (R = −0.72, p < 0.006 and R = −0.90, p < 0.001; R = −0.68, p < 0.01 and R = −0.71, p < 0.007). Task-related networks function differently in patients with PD in association with motor symptoms, whereas impaired modulation of visual and default-mode network connectivity was not correlated with motor function.

IN-HOME-PD: The effects of longitudinal telehealth-enhanced interdisciplinary home visits on care and quality of life for homebound individuals with Parkinson's disease

IntroductionHomebound individuals with advanced Parkinson's disease (PD) are underrepresented in research and care. We tested the impact of interdisciplinary, telehealth-enhanced home visits (IN-HOME-PD) on patient quality of life (QoL) compared with usual care. MethodsNonrandomized controlled trial of quarterly, structured, telehealth-enhanced interdisciplinary home visits focused on symptom management, home safety, medication reconciliation, and psychosocial needs (ClinicalTrials.gov NCT03189459). We enrolled homebound participants with advanced PD (Hoehn & Yahr (HY) stage ≥3). Usual care participants had ≥2 visits in the Parkinson's Outcomes Project (POP) registry. We compared within- and between-group one-year change in QoL using the Parkinson's Disease Questionnaire. ResultsSixty-five individuals enrolled in IN-HOME-PD (32.3% women; mean age 78.9 (SD 7.6) years; 74.6% white; 78.5% HY ≥ 4) compared with 319 POP controls, with differences in age, race, and PD severity (37.9% women; mean age 70.1 (7.8) years; 96.2% white; 15.1% HY ≥ 4). Longitudinally, the intervention group's QoL remained unchanged (within-group p = 0.74, Cohen's d = 0.05) while QoL decreased over time in POP controls (p < 0.001, Cohen's d = 0.27). The difference favored the intervention (between-group p = 0.04). POP participants declined in 7/8 dimensions while IN-HOME-PD participants' bodily discomfort improved and hospice use and death at home—markers of goal-concordant care—far exceeded national data. ConclusionsTelehealth-enhanced home visits can stabilize and may improve the predicted QoL decline in advanced PD via continuity of care and facilitating goal-concordant care, particularly among diverse populations. Extrapolating features of this model may improve continuity of care and outcomes in advanced PD.

COGNITIVE DYSFUNCTION IN PARKINSON DISEASE

Parkinson’s disease is the second most common progressive neurodegenerative disorder mainly in middle-elderly population. Particular attention is paid to the evaluation and correction of cognitive disorders among non-motor manifestations of the disease. The purpose of this scientific study was to study the features of clinical deficiency in Parkinson's disease. The study included 36 patients who underwent clinical and neurological assessment, as well as neuropsychological testing according to the MOCA and Hoehn Yahr scales. Thus, according to the results of the study, a direct correlation was found between the severity of the disease and the degree of cognitive impairment.

Diagnostic value of striatal 18F-FP-DTBZ PET in Parkinson's disease.

Background18F-FP-DTBZ has been proven as a biomarker for quantifying the concentration of presynaptic vesicular monoamine transporter 2 (VMAT2). However, its clinical application is still limited.ObjectivesTo evaluate the difference in dopaminergic integrity between patients with Parkinson’s disease (PD) and healthy controls (HC) using 18F-FP-DTBZ PET in vivo and to determine the diagnostic value of standardized uptake value ratios (SUVRs) using the Receiver Operating Characteristic (ROC) curve.MethodsA total of 34 PD and 31 HC participants were enrolled in the PET/MR derivation cohort, while 89 PD and 18 HC participants were recruited in the PET/CT validation cohort. The Hoehn–Yahr Scale and the third part of the MDS-Unified Parkinson’s Disease Rating Scale (MDSUPDRS-III) were used to evaluate the disease staging and severity. All assessments and PET scanning were performed in drug-off states. The striatum was segmented into five subregions as follows: caudate, anterior dorsal putamen (ADP), anterior ventral putamen (AVP), posterior dorsal putamen (PDP), and posterior ventral putamen (PVP) using automatic pipeline built with the PMOD software (version 4.105). The SUVRs of the targeted subregions were calculated using the bilateral occipital cortex as the reference region.ResultsRegarding the diagnostic value, ROC curve and blind validation showed that the contralateral PDP (SUVR = 3.43) had the best diagnostic accuracy (AUC = 0.973; P < 0.05), with a sensitivity of 97.1% (95% CI: 82.9–99.8%), specificity of 100% (95% CI: 86.3–100%), positive predictive value (PPV) of 100% (95% CI: 87.0–100%), negative predictive value (NPV) of 96.9% (95% CI: 82.0–99.8%), and an accuracy of 98.5% for the diagnosis of PD in the derivation cohort. Blind validation of 18F-FP-DTBZ PET imaging diagnosis was done using the PET/CT cohort, where participants with a SUVR of the PDP <3.43 were defined as PD. Kappa test showed a consistency of 0.933 (P < 0.05) between clinical diagnosis and imaging diagnosis, with a sensitivity of 98.9% (95% CI: 93.0–99.9%), specificity of 94.4% (95% CI: 70.6–99.7%), PPV of 98.9% (95% CI: 93.0–99.9%), NPV of 94.4% (95% CI: 70.6–99.7%), and a diagnostic accuracy of 98.1%.ConclusionsOur results showed that an SUVR threshold of 3.43 in the PDP could effectively distinguish patients with PD from HC.