Dose-response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson's disease: a prospective, observational, cohort study.

Background: Exercise has been proposed as the "Universal Prescription for Parkinson's Disease"; however, the specificity of exercise dose in terms of frequency, intensity, duration, and type to be prescribed remains to be elucidated. The 2018 US updated guidelines and WHO Guidelines on Physical Activity and Sedentary Behavior recommend older adults (> 65+ years) to achieve weekly minimal activity levels, indicating the intensity of aerobic exercise as the metabolic equivalent of task and duration as minutes/week (150-300 min/week at a moderate intensity of 3-5.9 MET- or 75-150 min/week of a vigorous intensity of ≥6 MET). Translating these recommendations to PD patients, the study aimed to assess the dose-response effects of standardized volume of structured exercise, measured as METs-minutes/week (weekly energy expenditure) of two different rehabilitation settings to quantify the change in neurotrophic factors. The exercise-induced benefits between the two rehabilitation settings will be evaluated based on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life, and cortical activity and brain connectivity. Methods: METEX-PD is a pilot, prospective, observational, cohort study. The study will enroll consecutively thirty (N = 30) participants with mild-to-moderate Parkinson's disease diagnosis to be assigned to a non-intensive or intensive rehabilitation group. The non-intensive rehabilitation group will achieve a range of 180-270 METs-min/week (90 min/week of low-intensity aerobic exercise, 2-3 METs), while the intensive rehabilitation group will exercise at 1350-1980 METs-min/week (225 min/week of high-intensity aerobic exercise, 6-8.8 METs). The METEX-PD trial will last 12 weeks, including 4 weeks of aerobic training program and two follow-ups. Assessments will be performed at baseline (T0), at the end of the exercise program (T1-end of the program), and 4- and 8 weeks after the end of the training program (FU-1 and FU-2). The primary outcome is the change from baseline in peripheral blood BDNF levels. Secondary outcomes are differences in peripheral biomarkers, functional-motor assessments, clinical-functional evaluations, and brain imaging. Conclusion: METEX-PD trial will enable us to estimate the change in BDNF levels and other peripheral biomarkers under precise exercise-induced energy expenditure. The primary results of the METEX-PD study will allow the development of a larger multicenter randomized controlled trial to investigate the molecular pathways inducing the change in selected neurotrophic factors, such as BDNF, IGF-1, or irisin, and the downstream mechanisms of neuroplasticity in PD patients.

The Effects of Multidisciplinary Intensive Rehabilitation on Cognitive and Executive Functions in Parkinson's Disease: A Clinical Database Analysis.

Background/Objectives: This study is based on data collected from a medical health record review to assess whether multidisciplinary intensive rehabilitation treatment in Parkinson's disease (PD) patients can improve global cognitive functioning and executive functions. Methods: The data related to PD patients were extrapolated from a clinical database called "NeuroRehab". A total of 104 PD patients (51 males; 53 females) performed 6 weeks of multidisciplinary intensive rehabilitation treatment in clinical practice from January 2019 to May 2023. This training program was characterized by three daily sessions of 60 min of activities (muscle relaxation and stretching exercises, moderate physical aerobic exercise, and occupational therapy). The patients were classified and stratified according to disease severity (according to the Hoehn and Yahr scale), postural instability and gait difficulty (PIGD) or tremor-dominant (TD) subtypes, disease duration (DD), and the presence of dyskinesias. The effect of multidisciplinary intensive rehabilitation treatment on cognitive and executive functions was evaluated through the administration of cognitive tests, such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). All the parameters were evaluated at the baseline (T0) and at the end of the rehabilitation program (T1). Results: The multidisciplinary intensive rehabilitation treatment significantly improved cognitive performance. The MMSE, MoCA, and FAB test scores after the rehabilitation program (T1) were significantly higher compared to the scores obtained at the baseline (T0). Moreover, further analyses on subgroups of the patients who scored below the cut-off in the MMSE showed that at least 50% of patients overcame the cut-off score. Interestingly, the same analyses performed for the MoCA and FAB revealed a higher rate of improvement in cognitive functions, with normal scores in both tests after 6 weeks of multidisciplinary intensive rehabilitation treatment. Conclusions: This study revealed the potential effects of a 6-week multidisciplinary rehabilitation program in improving cognitive status in a PD inpatient cohort.

Advanced Parkinson's disease treatment patterns in Italy: an observational study interim analysis.

BACKGROUND: Oral levodopa remains the mainstay of treatment for Parkinson's disease (PD). However, as PD progresses, response to treatment may fluctuate. Managing fluctuations can be demanding for clinicians and patients. There is a paucity of real-world studies reporting on PD management in patients with fluctuations in treatment response, especially in patients with advanced stages of PD. The multicentre, observational Parkinson's Disease Fluctuations treatment PAthway (PD-FPA) study describes the real-life management of response fluctuations in Italian patients with advanced PD. PATIENTS AND METHODS: PD-FPA had a retrospective and prospective phase; herein, retrospective results are presented. Ten Italian centres enrolled patients with a PD diagnosis from 10-15 years prior to study entry (T0) and who had ≥2-year history of fluctuations. Data on patient demographics, medical history, PD stage, fluctuation characteristics, symptoms, and prescribed treatments were collected at T0 and retrospectively (2 years prior to T0) via patient chart review/interview. RESULTS: Overall, 296 patients (60% male, mean age 68 years, 84% with Hoehn and Yahr scores 2-3) were enrolled. At T0, most patients (99.3%) were on oral levodopa therapy. All patients used dopaminergic medications; adjunctive medications included dopamine agonists (56%) and monoamine oxidase B (60%) and catechol-O-methyltransferase enzyme inhibitors (41%). At T0, 51% of patients had changed therapy, with response fluctuations being the most common reason (74%); wearing-off was the most common fluctuation (83%). CONCLUSION: This interim analysis of PD-FPA suggests that adequate levodopa dosing and adjunctive medications can stabilize advanced PD and provide patients with a good quality of life.

Patients with Parkinson's disease (PD) often exhibit fluctuations in their response to oral levodopa; however, real-world studies on the management of these fluctuations are lacking. This planned interim analysis of the real-world, multicentre, observational PD Fluctuations treatment Pathway (PD-FPA) study found that adequate levodopa dosing and adjunctive medications can stabilize Italian patients with advanced PD and improve their quality of life.

Real-world use of Safinamide in motor fluctuating Parkinson's disease patients in Italy.

INTRODUCTION: Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. METHODS: We performed a sub-analysis of the Italian cohort of the SYNAPSES study, a multi-country, multi-center, retrospective-prospective cohort observational study, designed to investigate the use of safinamide in routine clinical practice. Patients received for the first time a treatment with safinamide and were followed up for 12 months. The analysis was conducted on the overall population and in subgroups of interest: i) patients > 75 years, ii) patients with relevant comorbidities and iii) patients affected by psychiatric symptoms. RESULTS: Italy enrolled 616/1610 patients in 52 centers, accounting for 38% of the entire SYNAPSES cohort. Of the patients enrolled, 86.0% were evaluable at 12 months, with 23.3% being > 75 years, 42.4% with psychiatric conditions and 67.7% with relevant comorbidities. Safinamide was effective on motor symptoms and fluctuations as measured through the Unified PD rating scale III and IV scores, and on the total score, without safety issues in none of the subgroups considered. CONCLUSION: The SYNAPSES data related to Italian patients confirms the good safety profile of safinamide even in special groups of patients. Motor fluctuations and motor impairment improved at the follow-up suggesting the significant role of safinamide in managing motor symptoms in PD patients.

Poor reactivity of posterior electroencephalographic alpha rhythms during the eyes open condition in patients with dementia due to Parkinson's disease.

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.

Physical activity and neurotrophic factors as potential drivers of neuroplasticity in Parkinson's Disease: A systematic review and meta-analysis.

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by motor and non-motor symptoms, that still lacks of a disease-modifying treatment. Consistent evidence proved the benefits of physical therapy on motor and non-motor symptoms in PD patients, leading the scientific community to propose physical activity as disease-modifying therapy for PD and suggesting the involvement of neurotrophic factors (NFs) as key mediators of neuroplasticity. However, the lack of standardized exercise training and methodological flaws of clinical trials have limited the evidence demonstrating the exercise-induced changes in serum and plasma neurotrophic factors concentration. A systematic search, covering 20 years of research in this field and including randomized and non-randomized controlled trials (RCTs and non-RCTs), which reported changes in serum and plasma NFs after a specific intervention, were reviewed. Pooled effect sizes (p-ESs) and 95% confidence intervals (95%CIs) were calculated using a random effects model with R software. A total of 18 articles, of which exercise programs of interventions were codified in terms of type, intensity and duration adopting a standardisation methodology, were included in the systematic review. Six papers, describing the effect of different training programs on BDNF and IGF-1 levels, were included and independently analysed in two meta-analyses. Quantitative analysis for BDNF indicated a statistically significant improvement in serum concentration of PD patients (MD: 5.99 ng/mL; 95%IC: 0.15 -11.83; I2 = 77%) performing physical activity compared with control conditions in RCTs. Preliminary evidence supported the hypothesis that a moderate intensity aerobic exercise (MIAE) would be necessary to induce the changes in NFs. However, sensitivity analysis of meta-analysis and the few studies included in subgroup analysis did not support these results. Alongside, meta-analysis followed by sensitivity analysis revealed a potential change in serum IGF-1 (MD: 33.47 ng/mL; 95%IC: 8.09-58.85) in PD patients performing physical activity with respect controls in RCT studies. Considering the limited evidence to support or refute the increase in NFs levels in PD patients performing physical activity, there is a need to develop a rigorous controlled randomized trial, with standardization for loading intensity of physical activity, greater sample size, and a correct stratification of PD patients to establish a well-defined correlation between physical activity and NFs levels.

Therapeutic education for empowerment and engagement in patients with Parkinson's disease: A non-pharmacological, interventional, multicentric, randomized controlled trial.

Background: In 1997 the European Parkinson's Disease Associations launched the Charter for People with Parkinson's disease that stated the right of patients to be informed and trained on the disease, its course, and treatments available. To date, few data analyzed the effectiveness of education program on motor and non-motor symptoms of PD. Objective: The aim of this study was to evaluate the efficacy of an education program as it was a pharmacological treatment, thus choosing as the primary endpoint the change in daily OFF hours, the most widely used outcome in pharmaceutical clinical trials on PD patients with motor fluctuations. Secondary outcomes were change in motor and non-motor symptoms, quality of life and social functioning. The long-term efficacy of the education therapy was also evaluated by analyzing data collected at 12- and 24-weeks follow-up outpatient visits. Methods: One hundred and twenty advanced patients and their caregivers were assigned to the intervention or control group in a single-blind, multicentric, prospective, randomized study evaluating an education program structured in individual and group sessions over a 6-weeks period.At the end of study, the intervention group showed a significant reduction in daily OFF hours compared to control patients (-1.07 ± 0.78 vs. 0.09 ± 0.35, p < 0.0001) and a significant improvement was also reported in most secondary outcomes. Patients retained significant medication adherence and daily OFF hours reduction at 12- and 24-weeks follow-up. Conclusion: The results obtained demonstrated that education programs may translate in a notable improvement in motor fluctuations and non-motor symptoms in advanced PD patients.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04378127.

A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease.

A randomized thorough QT study was conducted to assess the effects of apomorphine sublingual film (SL-APO) on corrected QT interval (QTc) and other cardiac conduction parameters in patients with Parkinson's disease (PD) and "OFF" episodes. Patients were titrated to an SL-APO dose that resulted in FULL "ON," followed by up to two additional doses (maximum 60 mg), then randomized at the highest tolerated dose to a treatment sequence of SL-APO, placebo, and moxifloxacin (400 mg, positive control) in a three-way crossover design. Changes from baseline in time-matched, placebo-adjusted Fridericia-corrected QTc interval (ΔΔQTcF) and Bazett-corrected QTc interval (ΔΔQTcB) were analyzed from postdose electrocardiograms. Forty patients were randomized and received single doses of study treatments. Upper limits of 90% confidence intervals (CIs) for ΔΔQTcF of SL-APO were below the 10-millisecond regulatory threshold at all prespecified timepoints, demonstrating no clinically significant effect on QTcF. Lower limits of 90% CIs for ΔΔQTcF of moxifloxacin exceeded the 5-millisecond regulatory threshold at all timepoints up to 3 hours, confirming assay sensitivity. SL-APO had no clinically meaningful effects on QTcB, PR/QRS intervals, heart rate, or electrocardiogram-derived morphology (EudraCT identifier: 2016-001762-29; ClinicalTrials.gov identifier: NCT03187301).

Reactivity of posterior cortical electroencephalographic alpha rhythms during eyes opening in cognitively intact older adults and patients with dementia due to Alzheimer's and Lewy body diseases.

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients.

Dose optimization of apomorphine sublingual film for treating "OFF" episodes in Parkinson's disease.

INTRODUCTION: Apomorphine sublingual film is approved for the "on-demand" treatment of "OFF" episodes in Parkinson's disease (PD). Patients must undergo dose titration to determine their most effective and tolerable dose. We assessed whether higher doses than those that provide an initial "ON" response could yield more effective treatment. METHODS: Patients with PD were assessed in the "OFF" state and the apomorphine sublingual film dose was titrated to a level that provided a tolerable "ON" response. The dose was then increased by up to two dose levels, if tolerated. A comparison in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III scores was made following administration of the dose that provided the initial "ON" response and following the higher dose. Treatment-emergent adverse events were also reported. RESULTS: Thirty-five patients were titrated to higher apomorphine sublingual film doses than those that provided an initial "ON" response. A mean improvement in MDS-UPDRS Part III score was observed compared with the initial dose of 5.6 points (P = 0.034), 4.4 points (P = 0.009), and 3.7 points (P = 0.018) at 30, 60, and 90 min postdose, respectively. Adverse events were mild or moderate and resolved with dose reduction without concomitant treatment. CONCLUSION: Higher doses of apomorphine sublingual film than those initially perceived to provide an "ON" response can be tolerated and provide additional improvement in motor function in many patients.

Sensor Network for Analyzing Upper Body Strategies in Parkinson's Disease versus Normative Kinematic Patterns.

In rehabilitation, the upper limb function is generally assessed using clinical scales and functional motor tests. Although the Box and Block Test (BBT) is commonly used for its simplicity and ease of execution, it does not provide a quantitative measure of movement quality. This study proposes the integration of an ecological Inertial Measurement Units (IMUs) system for analysis of the upper body kinematics during the execution of a targeted version of BBT, by able-bodied persons with subjects with Parkinson's disease (PD). Joint angle parameters (mean angle and range of execution) and hand trajectory kinematic indices (mean velocity, mean acceleration, and dimensionless jerk) were calculated from the data acquired by a network of seven IMUs. The sensors were applied on the trunk, head, and upper limb in order to characterize the motor strategy used during the execution of BBT. Statistics revealed significant differences (p < 0.05) between the two groups, showing compensatory strategies in subjects with PD. The proposed IMU-based targeted BBT protocol allows to assess the upper limb function during manual dexterity tasks and could be used in the future for assessing the efficacy of rehabilitative treatments.

Plant isoquinoline alkaloids as potential neurodrugs: A comparative study of the effects of benzo[c]phenanthridine and berberine-based compounds on ß-amyloid aggregation.

Herein we present a comparative study of the effects of isoquinoline alkaloids belonging to benzo[c]phenanthridine and berberine families on ß-amyloid aggregation. Results obtained using a Thioflavine T (ThT) fluorescence assay and circular dichroism (CD) spectroscopy suggested that the benzo[c]phenanthridine nucleus, present in both sanguinarine and chelerythrine molecules, was directly involved in an inhibitory effect of Aß1-42 aggregation. Conversely, coralyne, that contains the isomeric berberine nucleus, significantly increased propensity for Aß1-42 to aggregate. Surface Plasmon Resonance (SPR) experiments provided quantitative estimation of these interactions: coralyne bound to Aß1-42 with an affinity (KD = 11.6 µM) higher than benzo[c]phenanthridines. Molecular docking studies confirmed that all three compounds are able to recognize Aß1-42 in different aggregation forms suggesting their effective capacity to modulate the Aß1-42 self-recognition mechanism. Molecular dynamics simulations indicated that coralyne increased the ß-content of Aß1-42, in early stages of aggregation, consistent with fluorescence-based promotion of the Aß1-42 self-recognition mechanism by this alkaloid. At the same time, sanguinarine induced Aß1-42 helical conformation corroborating its ability to delay aggregation as experimentally proved in vitro. The investigated compounds were shown to interfere with aggregation of Aß1-42 demonstrating their potential as starting leads for the development of therapeutic strategies in neurodegenerative diseases.

Effect of family history, occupation and diet on the risk of Parkinson disease: A case-control study.

BACKGROUND: The aetiology of Parkinson's disease (PD) is still very controversial, with a peculiar lack of established risk factors or protective behavior. METHODS: We carried out a case-control study of 634 idiopathic PD patients admitted from 2011 to 2015 to two hospitals located in central Italy and 532 controls matched by hospital, gender and age (± 5 years). The study questionnaire included questions on host factors, family history, residence, occupation and lifestyle. Odds ratios (ORs) for PD and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for actual and potential confounders. RESULTS: A lower OR was observed in females (0.74; 95%CI:0.58-0.96), while older age classes showed a constantly increased risk for PD (p<0.005) starting from the class 65-69 years. Subjects who reported a first degree relative affected by PD showed a borderline increase which was more evident in those enrolled in the urban center of Rome (OR = 1.65; 95%CI: 1.09-2.50). Significant reduction of the risk was associated to current smoking (OR = 0.48; 95%CI: 0.24-0.54), and to vegetables consumption (p<0.03), while borderline increases were associated to meat and cold cut consumption. Occupational activities classified according to ISCO-08 categories did not show increased risk, while higher ORs' were found for pilots and physicians. CONCLUSIONS: The results from this study confirmed the higher risk of PD in males and in elderly, and the inverse association with smoking habit. The possible etiological role of familial clustering, dietary habit, and some job tasks is suggested.

Abnormalities of resting-state EEG in patients with prodromal and overt dementia with Lewy bodies: Relation to clinical symptoms.

OBJECTIVE: Here we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms. METHODS: We extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer's disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources. RESULTS: As compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB "controls", the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005). CONCLUSIONS: Relevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients. SIGNIFICANCE: Those features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies.

Magnetic resonance parkinsonism indices and interpeduncular angle in idiopathic normal pressure hydrocephalus and progressive supranuclear palsy.

PURPOSE: The clinical presentation of idiopathic normal pressure hydrocephalus (iNPH) may overlap with progressive supranuclear palsy (PSP). The Magnetic Resonance Parkinsonism Index (MRPI), MRPI 2.0, and the interpeduncular angle (IPA) have been investigated to differentiate PSP from healthy controls (HC) and other parkinsonisms. We aimed to assess equivalences and differences in MRPI, MRPI 2.0, and IPA in iNPH, PSP, and HC groups. METHODS: We retrospectively recruited 99 subjects (30 iNPH, 32 PSP, 37 HC) from two institutions. MRI exams, acquired on either 1.5 T or 3 T scanners, included 3D T1-weighted images to measure MRPI, MRPI 2.0, and IPA. Inter- and intra-rater reliability was investigated with the intra-class correlation coefficient (ICC), and the two one-sided t tests (TOST) procedure was used to assess these markers in iNPH, PSP, and HC. RESULTS: For all the three measures, intra-rater and inter-rater ICC were excellent (range = 0.91-0.93). In the comparison of iNPH and PSP with HC, differences for MRPI and MRPI 2.0 (p < 0.01 in all cases) and no equivalence (p = 1.00 in all cases) were found at TOST. iNPH and PSP MRPI showed no difference (p = 0.06) and no equivalence (p = 0.08). MRPI 2.0 was not equivalent (p = 0.06) and not different (p = 0.09) in the same two populations. PSP and HC IPA proved equivalent (p < 0.01) while iNPH IPA was different (p < 0.01) and not equivalent (p = 0.96 and 0.82) from both PSP and HC. CONCLUSION: MRPI and MRPI 2.0 significantly overlap in iNPH and PSP, with risk of misdiagnosis, and for this reason may not be helpful in the differential diagnosis.

Abnormal cortical neural synchronization mechanisms in quiet wakefulness are related to motor deficits, cognitive symptoms, and visual hallucinations in Parkinson's disease patients: an electroencephalographic study.

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N = 136) and Alzheimer's disease patients (AD, N = 85), and healthy older participants (Nold, N = 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness.

A novel summary kinematic index for postural characterization in subjects with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological disorder characterized, among other symptoms, by a significant modified posture. Although a detailed assessment of postural abnormalities can be performed using quantitative movement analysis, the output of such procedure might be not suitable for a routine clinical use due to its intrinsic complexity. However, synthetic measures may facilitate the interpretation of kinematic data for physicians and thus make such tools fully exploitable in daily practice. AIM: According to these considerations, the aim of the present study is to propose a new summary index, the Postural Profile Score (PPS, together with its constituent variables: Postural Variable Scores [PVSs]), which can characterize the postural kinematic biomechanical profile of an individual; this approach was then applied to a cohort of individuals with PD. DESIGN: Controlled observational study. SETTING: Movement Analysis Laboratory of Hospital. POPULATION: Forty-five individuals with PD in mild to severe disability stage, of mean age 65.9 (SD 8.3) years and 21 healthy control age-matched (CG) were tested using an optoelectronic system during bipedal quiet standing. METHODS: Twelve joint angles of trunk and of lower limbs, considered representative of the whole-body posture according to Davis protocol, were acquired and the root mean square (RMS) difference between them and those of the unaffected participants (PVSs) were computed. Then, the PPS was calculated as a combination of the selected PVSs. The existence of possible differences between people with PD and controls for PPS and PVSs was assessed using MANOVA test. UPDRS III score was also considered in order to assess existence of correlation between synthetic indexes and Clinical scales values. RESULTS: Significant differences in PPS were detected between PD and CG (8.59° vs. 6.11°, P<0.001) and in some of the considered PVS (Trunk Sagittal, Trunk Frontal, Trunk Transversal, Hip flexion-extension, Hip abdo-adduction and Knee flexion-extension). Significant positive correlations were found between Clinical scales Vs trunk and ankle orientation. CONCLUSIONS: PPS could represent a reliable summary index of global postural abnormalities in people with PD, and in particular some PVSs appear more suitable to describe the deviation from a physiologic postural pattern. The results demonstrate that the posture in the patient with PD is modified compared to the control group. In particular, the trunk is the body district which mainly characterizes the alteration of the posture as documented by its PVSs values and their correlation with clinical evaluation scales. In conclusion, this study evidences the interest to measure the position of the trunk in order to characterize the postural kinematic position in individuals with PD. CLINICAL REHABILITATION IMPACT: PPS could be a useful tool for the characterization of postural phenotype in subjects with Parkinson's disease and could provide indications for specific rehabilitation protocols.

Clinical effects of robot-assisted gait training and treadmill training for Parkinson's disease. A randomized controlled trial.

BACKGROUND: Although gait disorders strongly contribute to perceived disability in people with Parkinson's disease, clinical trials have failed to identify which task-oriented gait training method can provide the best benefit. Freezing of gait remains one of the least investigated and most troublesome symptoms. OBJECTIVE: We aimed to compare the effects of robot-assisted gait training and treadmill training on endurance and gait capacity in people with Parkinson disease; the secondary aim was to compare the effect of the treatments in people with freezing and/or severe gait disability and assess changes in overall disease-related disability and quality of life. METHODS: Outpatients with Parkinson disease (Hoehn and Yahr stage≥2) were randomly assigned to receive 20 sessions of 45-min gait training assisted by an end-effector robotic device (G-EO System) or treadmill training. Outcome assessments were the 6-min walk test, Timed Up and Go test, Freezing of Gait Questionnaire, Unified Parkinson's Disease Rating Scales and Parkinson's Disease Quality of Life Questionnaire-39 administered before (T0) and after treatment (T1). RESULTS: We included 96 individuals with Parkinson disease: 48 with robot-assisted gait training and 48 treadmill training. Both groups showed significant improvement in all outcomes. As compared with baseline, with robot-assisted gait training and treadmill training, endurance and gait capacity were enhanced by 18% and 12%, respectively, and motor symptoms and quality of life were improved by 17% and 15%. The maximum advantage was observed with the Freezing of Gait Questionnaire score, which decreased by 20% after either treatment. On post-hoc analysis, dependent walkers benefited more than independent walkers from any gait training, whereas freezers gained more from robot-assisted than treadmill training in terms of freezing reduction. CONCLUSIONS: Repetitive intensive gait training is an effective treatment for people with Parkinson disease and can increase endurance and gait velocity, especially for those with severe walking disability. Advantages are greater with robot-assisted gait training than treadmill training for individuals with freezing of gait - related disability.

Abnormalities of functional cortical source connectivity of resting-state electroencephalographic alpha rhythms are similar in patients with mild cognitive impairment due to Alzheimer's and Lewy body diseases.

Previous evidence has shown different resting-state eyes-closed electroencephalographic delta (<4 Hz) and alpha (8-10.5 Hz) source connectivity in subjects with dementia due to Alzheimer's (ADD) and Lewy body (DLB) diseases. The present study tested if the same differences may be observed in the prodromal stages of mild cognitive impairment (MCI). Here, clinical and resting-state eyes-closed electroencephalographic data in age-, gender-, and education-matched 30 ADMCI, 23 DLBMCI, and 30 healthy elderly (Nold) subjects were available in our international archive. Mini-Mental State Evaluation (MMSE) score was matched in the ADMCI and DLBMCI groups. The eLORETA freeware estimated delta and alpha source connectivity by the tool called lagged linear connectivity (LLC). Area under receiver operating characteristic curve (AUROCC) indexed the classification accuracy among individuals. Results showed that widespread interhemispheric and intrahemispheric LLC solutions in alpha sources were abnormally lower in both MCI groups compared with the Nold group, but with no differences were found between the 2 MCI groups. AUROCCs of LLC solutions in alpha sources exhibited significant accuracies (0.72-0.75) in the discrimination of Nold versus ADMCI-DLBMCI individuals, but not between the 2 MCI groups. These findings disclose similar abnormalities in ADMCI and DLBMCI patients as revealed by alpha source connectivity. It can be speculated that source connectivity mostly reflects common cholinergic impairment in prodromal state of both AD and DLB, before a substantial dopaminergic derangement in the dementia stage of DLB.