Parkinson's Disease Severity Research Articles

Assessment of Parkinson's Disease Severity From Videos Using Deep Architectures.

Parkinson's disease (PD) diagnosis is based on clinical criteria, i.e., bradykinesia, rest tremor, rigidity, etc. Assessment of the severity of PD symptoms with clinical rating scales, however, is subject to inter-rater variability. In this paper, we propose a deep learning based automatic PD diagnosis method using videos to assist the diagnosis in clinical practices. We deploy a 3D Convolutional Neural Network (CNN) as the baseline approach for the PD severity classification and show the effectiveness. Due to the lack of data in clinical field, we explore the possibility of transfer learning from non-medical dataset and show that PD severity classification can benefit from it. To bridge the domain discrepancy between medical and non-medical datasets, we let the network focus more on the subtle temporal visual cues, i.e., the frequency of tremors, by designing a Temporal Self-Attention (TSA) mechanism. Seven tasks from the Movement Disorders Society - Unified PD rating scale (MDS-UPDRS) part III are investigated, which reveal the symptoms of bradykinesia and postural tremors. Furthermore, we propose a multi-domain learning method to predict the patient-level PD severity through task-assembling. We show the effectiveness of TSA and task-assembling method on our PD video dataset empirically. We achieve the best MCC of 0.55 on binary task-level and 0.39 on three-class patient-level classification.

Shuffling Improves the Acute and Carryover Effect of Subthalamic Coordinated Reset Deep Brain Stimulation.

Coordinated reset deep brain stimulation (CR DBS) in the subthalamic nucleus (STN) has been demonstrated effective for the treatment of the motor signs associated with Parkinson's disease (PD). A critical CR parameter is an order in which stimulation is delivered across contacts. The relative effect of alternating vs. not alternating this order, i.e., shuffling vs. non-shuffling, however, has not been evaluated in vivo. The objective of this study is to compare the effect of shuffled vs. non-shuffled STN CR DBS on Parkinsonian motor signs. Two Parkinsonian non-human primates were implanted with a DBS lead in the STN. The effects of STN CR DBS with and without shuffling were compared with the traditional isochronal DBS (tDBS) using a within-subject design. For each stimulation setting, DBS was delivered for 2 or 4 h/day for 5 consecutive days. The severity of PD was assessed using a modified clinical rating scale immediately before, during, and 1 h after DBS, as well as on days following the discontinuation of the 5 days of daily stimulation, i.e., carryover effect. Shuffled STN CR DBS produced greater acute and carryover improvements on Parkinsonian motor signs compared with non-shuffled CR. Moreover, this difference was more pronounced when more effective stimulation intensity and burst frequency settings were used. tDBS showed limited carryover effects. Given the significant effect of shuffling on the effectiveness of CR DBS, it will be critical for future studies to further define the relative role of different CR parameters for the clinical implementation of this novel stimulation paradigm.

Caring for a loved one with Parkinson's disease: the role of coping styles and relationship quality.

Informal carers play an essential role in the care of individuals with Parkinson's disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers' coping style, relationship quality, and carer burden. Cross-sectional. Thirty-nine PD patient carer dyads were included in the study. Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory. Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers' perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer's gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden. The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.

Novel machine learning-based hybrid strategy for severity assessment of Parkinson's disorders.

Parkinson's disease (PD) severity assessment in clinical settings largely depends on expertise level of clinicians which have inherent limitations and non-uniformity. Instrumented gait analysis plays a significant role in disease diagnosis and management. However, these are agonized from data dispersion due to demography, anthropometry, and self-selected walking speed of an individual. This research work aims to develop computationally efficient hybrid strategy using normalized features for PD severity evaluation. The relevance of each considered gait feature in demonstrating the outcomes is explained through feature importance and partial dependence plot (PDP) to build substantial insight for clinical needs. Gait, a biomarker, is used to access human mobility by utilizing vertical ground reaction force (VGRF) data of 72 healthy and 93 Parkinson's individuals. A multi-variate normalization approach identifies gait differences between PD and non-PD. The proposed hybrid model used is able to detect PD with accuracy of 99.39% and 99.9%, and its severity assessment based on MDS-UPDRS-III shows coefficient of determination (R2) as 97% and 98.7% using leave-one-out cross-validation (CV) and tenfold CV respectively. The significant features suitable for clinical implications are reported. Moreover, normalized gait parameters supplement capability to compare individuals with diverse physical properties, resulting in assistive system for evaluation of PD severity.

White matter damage in patients with mild cognitive impairment in Parkinson's disease.

This study investigates the correlation between white matter structural damage and cognitive impairment in patients with Parkinson's disease (PD) and mild cognitive impairment (MCI). A total of 40 patients with PD were divided into two groups, i.e., a mild cognitive impairment (PD-MCI) and a normal cognitive (PDN) group, and 20 healthy patients were enrolled as the control group. Changes in the white matter structure of patients with PD were evaluated using diffusion tensor imaging (DTI), and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) scale and Mini-Mental State Examination (MMSE). Finally, the correlations between the two groups were analyzed. The Unified Parkinson's Disease Rating Scale score was significantly higher in the PD-MCI than in the PDN group (P=0.008). The total MoCA and MMSE scores in the PD-MCI group were significantly lower than in the PDN and control groups (P<0.01). Patients in PDMCI group were tested by MMSE scale, and the abnormal score rate was 60.0%. Among them, 8 PD patients with normal MMSE total score were found to have mild cognitive impairment by MoCA evaluation. When compared with the PDN and control groups, the MoCA scores for visual space, which is assessed as part of the MoCA scale and generally represents bilateral parietal function; naming; memory; and attention were significantly lower in the PD-MCI group (P<0.001). When compared with the PDN group, the fractional anisotropy (FA) values for the right parietal and left occipital lobes were significantly lower in the PD-MCI group (P=0.005; P=0.018). The relationship between MoCA value and right parietal white matter and left occipital white matter was 0.555, 0.474, respectively. A Pearson's correlation test was conducted to compare the FA values and MoCA scores of the various brain areas in the PD-MCI group and revealed a significant positive correlation between the MoCA score and the white matter of the right parietal and left occipital lobes (P<0.01). Patients with PD experience early cognitive impairment, and the MoCA scale can be used for early screening. In addition, the DTI of white matter can highlight early white matter damage. In the current study, the damaged brain areas displayed by DTI were consistent with areas showing decreased MoCA scores and were positively correlated with the severity of PD.

A digital seed amplification assay for the quantitative diagnosis of Parkinson’s disease

The process of forming amyloid fibrils from misfolded proteins occurs through a nucleation-dependent polymerization reaction, which has also been studied in the context of neurodegenerative diseases, including Parkinson's disease (PD). PD severity is strongly correlated with the accumulation of intraneuronal α-synuclein aggregates, making pathological α-synuclein isoforms promising biomarkers for PD. α-synuclein aggregates can be detected using seed amplification assays (SAAs), however, these assays are not quantitative and suffer from a lack of reproducibility.

Serum NFL discriminates Parkinson disease from essential tremor and reflect motor and cognition severity

ObjectiveTo investigate the diagnostic value of serum neurofilament light chain (NFL) for discriminating Parkinson disease (PD) from Essential tremor (ET) and healthy controls, and to evaluate its correlation with some clinical features of PD patients.MethodsThis cross-sectional study measured NFL levels with electrochemiluminescence immunoassay in serum of 146 PD patients, 82 ET patients and 60 age-matched healthy controls. We used multivariate regression analyses to examine whether NFL contributes to PD biomarkers. Disease severity were assessed by Unified Parkinson’s Disease Rating Scale part III (UPDRS III), Hoehn & Yahr (H-Y) stage and Mini-Mental State Examination (MMSE).ResultsSerum NFL levels were significantly higher in PD than in ET and healthy controls (16.6 ± 3.5, 12.2 ± 2.4 and 11.8 ± 2.4 pg/mL, respectively, p < 0.001). In patients with PD, serum NFL were markedly increased in patients with advanced H-Y stage and patients with dementia (both p < 0.001). The correlation analysis revealed that serum NFL was positively associated with UPDRS III score (r = 0.79, p < 0.001) and H-Y stage (r = 0.86, p < 0.001), and negatively correlated with MMSE scores (r = − 0.70, p < 0.001). Further multivariate regression analyses showed that serum NFL was an independent contributor to motor symptom and cognition severity in PD patients (all p < 0.01).ConclusionsSerum NFL levels were markedly elevated may be a useful clinical biomarker for discriminating PD patients from ET and controls. Serum NFL may serve as a potential blood biomarker for motor and cognition severity of PD.

Dopaminergic neuronal death in the substantia nigra associates with change in serum levels of TNF-α and IL-1β; evidence from early experimental model of Parkinson’s disease

ABSTRACT Purpose Studies have shown that inflammation plays a key role in etiology of Parkinson’s disease (PD). However, human studies which have evaluated association between PD and serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) have reported conflicting results. In this study, serum and striatum levels of these cytokines were evaluated in 6-hydroxydopamine (6-OHDA) animal model of PD. Method The neurotoxin of 6-OHDA was injected into medial forebrain bundle of right hemisphere and behavioral tests were carried out to eight weeks thereafter to evaluate severity of PD and its progress. Blood was collected before the toxin and in second and eight weeks after that. Survival of dopaminergic (DAergic) neurons in substantia nigra was assessed by immunohistochemistry. TNF-α and IL-1β levels were determined using ELISA kits. Result Severity of behavioral symptoms was gradually increased in 6-OHDA-treated rats. They showed a decrease in serum TNF-α level in the eight week and increase in IL-1β both in the second and eight weeks. They were divided into two subgroups, symptomatic and asymptomatic with severe and moderate degrees in DAergic neuronal death. Significant decrease in serum TNF-α was only observed in the symptomatic subgroup but IL-1β increased in both subgroups. Also, striatal levels of both cytokines were higher in the lesioned hemisphere. Conclusion Increase in serum IL-1β level can reflect moderate degree of lesion in substantia nigra and thereby is used for prognosis of PD before its clinical symptoms are appeared. On the other hand, an increase in serum TNF-α is appeared in advanced stage of PD.

Neurodegenerative changes of retina in Parkinson disease

In Parkinson’s disease (PD), some structural changes in the retina have been shown using optical coherence tomography (OCT). Among them most attractive are atrophic changes in retinal nerve fi ber layer (RNFL). However, diagnostic signifi cance of the OCT method in PD remains debatable. Objective: to investigate a thickness of RNFL in Parkinson’s disease patients and to determine the signifi cance of the OCT method in the PD diagnostics. Materials and methods. In PD patients (n = 24) and in a control group (n = 20) OCT was used to study the thickness of RNFL — average, in quadrants and in 10 sectors. Results. In patients with PD thinning of RNFL in the inferior quadrant was revealed (p = 0.009). The sensitivity and specifi city of the method were 56% and 82%, respectively. The thickness of RNFL was not associated with parkinsonian symptoms asymmetry, duration and severity of the disease. In the control group and in PD patients, there was a relationship between the RNFL thickness and age. Conclusion. PD is characterized by atrophic changes in the retina in the form of thinning of RNFL in the inferior quadrant, which confi rms the systemic nature of neurodegenerative pathology in this disease going beyond the substantia nigra and brain tissue. At the same time, the thickness of RNFL showed limited diagnostic value for detecting PD cases.

Swimming disorders in Parkinson's disease

To evaluate swimming disorders in patients with Parkinson's disease (PD). During the pilot study, we examined 40 patients with PD, who were divided into two groups depending on the presence or absence of swimming disorders. The assessment on the Hoehn-Yahr scale in both groups ranged from 1 to 3. The severity of PD was assessed according to the unified Parkinson's disease scale of the International Society of Movement Disorders (MDS-UPDRS). The Montreal Cognitive Assessment Scale, the Hospital Scale of Anxiety and Depression, a new questionnaire of freezing when walking, a 6-minute walk test, the Eysenck Personality Questionnaire were administered. Of 40 patients with PD, 60% reported swimming disorders. No association was found between swimming disorders and the severity of motor symptoms of PD. At the same time, an increased level of anxiety was noted in the group of patients with swimming disorders. Further research is needed to study the mechanisms of the development of swimming disorders in PD.

COVID-19: The cynosure of rise of Parkinson's disease.

Parkinson's disease (PD) is one of the most common age-related disorders globally. The pathophysiological mechanisms and precipitating factors underlying PD manifestations, including genetic and environmental parameters, inflammation/stress and ageing, remain elusive. Speculations about whether the Coronavirus Disease 2019 (Covid-19) pandemic could be a pivotal factor in affecting the prevalence and severity of PD or triggering a wave of new-onset parkinsonism in both the near and distant future have recently become very popular, with researchers wondering if there is a changing trend in current parkinsonism cases. Could the current understanding of the Covid-19 pathophysiology provide clues for an impending rise of parkinsonism cases in the future? Are there any lessons to learn from previous pandemics? Our aim was to look into these questions and available current literature in order to investigate if Covid-19 could constitute a cardinal event affecting the parkinsonism landscape.

Long non-coding RNA ANRIL interacts with microRNA-34a and microRNA-125a, and they all correlate with disease risk and severity of Parkinson's disease.

This study aimed to investigate the correlation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) and its target microRNAs (microRNA-34a (miR-34a) and microRNA-125a (miR-125a)) with disease risk and severity of Parkinson's disease (PD). Seventy-eight PD patients and 78 age-/gender-matched controls were consecutively enrolled. Their peripheral blood mononuclear cell samples were collected and proposed for the reverse-transcription quantitative polymerase chain reaction to complete lncRNA ANRIL, miR-34a, and miR-125a measurements. LncRNA ANRIL was upregulated, while miR-34a and miR-125a were downregulated in PD patients compared to controls (all p<0.001). Further, they all showed certain values for PD risk identification by ROC curve analyses, among which lncRNA ANRIL showed the highest AUC (AUC: 0.879, 95% CI: 0.824-0.934). Furthermore, lncRNA ANRIL negatively correlated with miR-34a (p=0.016) and miR-125a (p=0.005) in PD patients, but not in controls. In addition, lncRNA ANRIL was observed to positively associate with UPDRS-I score (p=0.029), UPDRS-III score (p=0.006), and UPDRS-IV score (p=0.033), while negatively correlated with MMSE score (p=0.003). These associations were less distinct as to miR-34a and miR-125a. LncRNA ANRIL interacts with miR-34a and miR-125a in PD patients, and they all correlate with disease risk and severity of PD.

Cardiovascular Metrics Associated With Prevention of Aging-Related Parkinsonian Signs Following Exercise Intervention in Sedentary Older Rats.

Preservation of motor capabilities is vital to maintaining independent daily living throughout a person's lifespan and may mitigate aging-related parkinsonism, a progressive and prevalent motor impairment. Physically active lifestyles can mitigate aging-related motor impairment. However, the metrics of physical activity necessary for mitigating parkinsonian signs are not established. Consistent moderate intensity (~10 m/min) treadmill exercise can reverse aging-related parkinsonian signs by 20 weeks in a 2-week on, 2-week off, regimen in previously sedentary advanced middle-aged rats. In this study, we initiated treadmill exercise in sedentary 18-month-old male rats to address two questions: (1) if a rest period not longer than 1-week off exercise, with 15 exercise sessions per month, could attenuate parkinsonian signs within 2 months after exercise initiation, and the associated impact on heart rate (HR) and mean arterial pressure (MAP) and (2) if continuation of this regimen, up to 20 weeks, will be associated with continual prevention of parkinsonian signs. The intensity and frequency of treadmill exercise attenuated aging-related parkinsonian signs by 8 weeks and were maintained till 23 months old. The exercise regimen increased HR by 25% above baseline and gradually reduced pre-intervention MAP. Together, these studies indicate that a practicable frequency and intensity of exercise reduces parkinsonian sign severity commensurate with a modest increase in HR after exercise. These cardiovascular changes provide a baseline of metrics, easily measured in humans, for predictive validity that practicable exercise intensity and schedule can be initiated in previously sedentary older adults to delay the onset of aging-related parkinsonian signs.

Psychosis in Parkinson's disease in a Southeast Asian cohort: prevalence and clinical correlates.

Psychosis is a prominent neuropsychiatric symptom of Parkinson's disease (PD) and is associated with negative outcomes, such as poorer quality of life and greater rate of functional impairment. Early identification of patients with PD at risk of developing psychosis facilitates appropriate management to improve outcomes. However, this phenomenon has not been examined locally. This study aimed to examine the prevalence of PD-associated psychosis in the local setting, identify any associated risk factors, as well as characterise the cognitive trajectory of patients with PD with psychosis. A retrospective cohort of 336 patients with PD, who presented to the National Neuroscience Institute, Singapore, in 2006 and 2007 and attended follow-up visits through to 2013 was analysed. The data analysed included scores from clinician assessments of cognitive function, disease severity and presence of psychotic symptoms, conducted when clinically appropriate during patients' medical visits. Survival analysis and logistic and linear regression analysis were performed. Psychosis was diagnosed in 63 patients with PD, indicating a prevalence of 18.8% for PD-associated psychosis. Incidence of psychosis in PD was calculated to be 40 per 1,000 person-years. No significant association was found between demographic variables and the odds of developing psychosis in PD. Regression analyses found that the presence of psychosis significantly predicted greater cognitive decline and disease severity. Psychosis has a significant presence among the PD population in Singapore, possibly serving as an indicator of more rapid cognitive decline and progression of PD severity.

Reduced Immunosenescence of Peripheral Blood T Cells in Parkinson's Disease with CMV Infection Background.

Immunosenescence is a process of remodeling the immune system under the influence of chronic inflammation during aging. Parkinson’s disease (PD) is a common age-associated neurodegenerative disorder and is frequently accompanied by neuroinflammation. On the other hand, cytomegalovirus (CMV), one of the most spread infections in humans, may induce chronic inflammation which contributes to immunosenescence, differentiation and the inflation of T cells and NK cells. Currently, there is no clear understanding of immunosenescence severity in PD patients infected with CMV. In this study, we analyzed differentiation stages and immunosenescence characteristics of T cells and NK cells in 31 patients with mild and moderate PD severity, 33 age-matched and 30 young healthy donors. The PD patients were 100% CMV-seropositive compared to 76% age-matched and 73% young CMV-infected healthy donors. The proportion of effector memory T cells re-expressing CD45RA, CD57+CD56− T cells and CD57+CD56+ T cells was significantly reduced in PD patients compared with CMV-seropositive age-matched healthy individuals. The CD57+CD56− T cell proportion in PD patients was similar to that of CMV-seropositive young healthy donors. Thus, PD is characterized by reduced peripheral blood T cell immunosenescence, even against the background of CMV infection.

Sleep Disturbances and Associated Factors in Drug-Naïve Patients with Parkinson's Disease.

PurposeSleep disturbance is one of the common symptoms in Parkinson’s disease (PD). The study of sleep disturbance used to concentrate on treated PD. This study aimed to investigate the factors that are associated with the sleep quality of drug-naïve patients with PD.Patients and MethodsAll participants were interviewed using a standard questionnaire to collect basic information. PD severity, depression symptoms, anxiety symptoms, sleep quality, cognitive status, life quality, and the presence of rapid eye movement (REM) sleep behavior disorder (RBD) and minor hallucination were assessed using corresponding rating scales. The patients with a Pittsburgh Sleep Quality Index score ≤6 fell into the poor sleep group, and those with REM Sleep Behavior Disorder Screening Questionnaire score ≥5 were considered to have probable RBD.ResultsSeventy drug-naive patients with PD and 30 healthy controls matched for age, sex, and education were recruited. Up to 41.4% of the patients suffered from sleep disturbance, and 24.3% of the patients had RBD. Poor sleepers were more likely to have left-side predominant motor symptoms. Compared with good sleepers, poor sleepers, particularly female patients, had more burden in the aspect of anxiety and depression. RBD was associated with more nonmotor symptoms, poor sleep quality, bad performance in cognition orientation domain, anxiety, depression, presence of minor hallucination, and poor life quality.ConclusionSleep disturbances are common in drug-naïve PD and require wide attention. Motor symptom laterality and gender difference in mood are associated with sleep quality. Depression, anxiety, and RBD are highly related to sleep disturbance. RBD has many comorbidities, which can influence the cognitive function and life quality of the patients.

LOWER URINARY TRACT SYMPTOMS IN NIGERIAN MEN WITH PARKINSONS DISEASE

Introduction: Parkinsons disease (PD) is the commonest age related motoric neurodegenerative disease. It results from the destruction of dopaminergic cell in the substantial nigra in the midbrain. In addition to the typical motor Parkinsonism symptoms, non -motor manifestations affect multiple organs including the lower urinary tract and contribute to worsening the overall quality of life. The objective of this study is to highlight the bother from lower urinary tract symptoms in patients with PD and determine the relationship between the lower urinary symptoms and severity of PD. Materials and Methods: This is a descriptive cross-sectional study in patients with clinically diagnosed PD that were managed by the Neurology Unit, Neurology Unit, Department of Medicine University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria. They all filled the International Prostate Symptom Score and Quality of Life form. The severity of PD in each patient was assessed using Unified Parkinsons Disease Rating Scale (UPDRS). The data obtained was analyzed using SPSS Version 20. Results: There were 22 patients aged between 25-87years with a mean age of 59.36 ±15.58years. Nocturia (90.90%), frequency (59.10%) and urgency (59.10%) were the commonest LUTS, while straining was the least frequent (22.70 %). Majority had mild (59.09%)and moderate (27.27%) symptoms. There was a strong association between total IPSSand QoL scores that was statistically significant (p&lt;0.0001 r= +0.859). The degree of bother from LUTS, evaluated with the IPSS questionnaire was associated with worsening of PD symptoms assessed with UPDRS (p=0.012). There was a moderate positive correlation between the severity of PD and the degree of bother from LUTS in PD patients (r=+0.527) Conclusions: Irritative symptoms are very common in Parkinsons disease, with nocturia the commonest. There was a moderate positive correlation between the severity of PD and the degree of bother from LUTS. The IPSS questionnaire could be used in evaluating urinary dysfunction in PD patients in both genders.

Exercise Intolerance and Oxygen Desaturation in Patients with Parkinson's Disease: Triggers for Respiratory Rehabilitation?

The role that oxygen desaturation plays in exercise tolerance and its rehabilitative implications in patients with Parkinson’s disease (PD) are unclear. We aimed to test exercise tolerance and oxygen saturation levels both during exercise and at night in PD patients to better define their rehabilitative needs. In clinically stable PD patients, undergoing inpatient rehabilitation, and in “ON” phase, we prospectively assessed clinical data, sleepiness, comorbidities, PD severity (Hoehn&Yahr, HY), motor function (ADLs, UPDRSII and UPDRSIII, Barthel Index, Functional Independence Measure), balance, spirometry, respiratory muscles (MIP/MEP), peak cough expiratory flow (PCEF), continuous night oxygen monitoring, and meters at 6MWT. Of 55 patients analyzed (28 with moderate–severe PD, HY ≥ 2.5), 37% and 23% showed moderate–severe impairment on UPDRSII and UPDRSIII, respectively; 96% had reduced exercise tolerance and severe respiratory muscles impairment (MIP/MEP < 45% pred.); 21.8% showed desaturations during exercise; and 12.7% showed nocturnal desaturations. At multiple regression, low exercise tolerance and low mean nocturnal and exercise-induced saturation correlated with several respiratory and motor function and disability indices (all p < 0.03). Exercise tolerance, exercise-induced desaturations, and nocturnal desaturations were extremely frequent in PD patients and were worse in more severe PD patients. This suggests considering a combined role for motor and respiratory rehabilitation in these patients.

Neuro-Immunity and Gut Dysbiosis Drive Parkinson's Disease-Induced Pain.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1–2% of the population aged 65 and over. Additionally, non-motor symptoms such as pain and gastrointestinal dysregulation are also common in PD. These impairments might stem from a dysregulation within the gut-brain axis that alters immunity and the inflammatory state and subsequently drives neurodegeneration. There is increasing evidence linking gut dysbiosis to the severity of PD’s motor symptoms as well as to somatosensory hypersensitivities. Altogether, these interdependent features highlight the urgency of reviewing the links between the onset of PD’s non-motor symptoms and gut immunity and whether such interplays drive the progression of PD. This review will shed light on maladaptive neuro-immune crosstalk in the context of gut dysbiosis and will posit that such deleterious interplays lead to PD-induced pain hypersensitivity.

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.