Supplementing Best Care with Specialized Rehabilitation Treatment in Parkinson's Disease: A Retrospective Study by Different Expert Centers.

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson's disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson's Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson's Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.

Cognitive and Neuropsychiatric Features of COVID-19 Patients After Hospital Dismission: An Italian Sample.

Background and Aims: Recent studies suggest cognitive, emotional, and behavioral impairments occur in patients after SARS-CoV-2 infection. However, studies are limited to case reports or case series and, to our knowledge, few of them have control groups. This study aims to assess the prevalence of neuropsychological and neuropsychiatric impairment in patients after hospitalization. Methods: We enrolled 29 COVID+ patients (M/F: 17/12; age 58.41 ± 10.00 years; education 11.07 ± 3.77 years, 2 left handers) who needed hospitalization but no IC, about 20 days post-dismission, and 29 COVID- healthy matched controls. Neuropsychological and neuropsychiatric assessments were conducted via teleneuropsychology using the following tests: MMSE, CPM47, RAVLT, CDT, Digit-Span Forward/Backward, Verbal fluencies; BDI-II, STAI. People with previous reported cognitive impairment and neurological or psychiatric conditions were excluded. Clinical and demographics were collected. Comparison between groups was conducted using parametric or non-parametric tests according to data distribution (T-test, Mann Withney-U test; Chi-square goodness of fit). Within COVID+ group, we also evaluated the correlation between the cognitive and behavioral assessment scores and clinical variables collected. Results: Among COVID+, 62% had at least one pathological test (vs. 13% in COVID-; p = 0.000) and significantly worst performances than COVID- in RAVLT learning (42.55 ± 10.44 vs. 47.9 ± 8.29, p = 0.035), RAVLT recall (8.79 ± 3.13 vs. 10.38 ± 2.19, p = 0.03), and recognition (13.69 ± 1.47 vs. 14.52 ± 0.63, p = 0.07). STAI II was higher in COVID- (32.69 ± 7.66 vs. 39.14 ± 7.7, p = 0.002). Chi-square on dichotomous values (normal/pathological) showed a significant difference between groups in Digit backward test (pathological 7/29 COVID+ vs. 0/29 COVID-; p = 0.005). Conclusions: Patients COVID+ assessed by teleneuropsychology showed a vulnerability in some memory and executive functions (working memory, learning, delayed recall, and recognition). Intriguingly, anxiety was higher in the control group. Our findings therefore confirm the impact of COVID-19 on cognition even in patients who did not need IC. Follow-up is needed to evaluate the evolution of COVID-19-related cognitive deficit. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT05143320].

Optimization of cognitive assessment in Parkinsonisms by applying artificial intelligence to a comprehensive screening test.

The assessment of cognitive deficits is pivotal for diagnosis and management in patients with parkinsonisms. Low levels of correspondence are observed between evaluations assessed with screening cognitive tests in comparison with those assessed with in-depth neuropsychological batteries. A new tool, we named CoMDA (Cognition in Movement Disorders Assessment), was composed by merging Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). In total, 500 patients (400 with Parkinson's disease, 41 with vascular parkinsonism, 31 with progressive supranuclear palsy, and 28 with multiple system atrophy) underwent CoMDA (level 1-L1) and in-depth neuropsychological battery (level 2-L2). Machine learning was developed to classify the CoMDA score and obtain an accurate prediction of the cognitive profile along three different classes: normal cognition (NC), mild cognitive impairment (MCI), and impaired cognition (IC). The classification accuracy of CoMDA, assessed by ROC analysis, was compared with MMSE, MoCA, and FAB. The area under the curve (AUC) of CoMDA was significantly higher than that of MMSE, MoCA and FAB (p < 0.0001, p = 0.028 and p = 0.0007, respectively). Among 15 different algorithmic methods, the Quadratic Discriminant Analysis algorithm (CoMDA-ML) showed higher overall-metrics performance levels in predictive performance. Considering L2 as a 3-level continuous feature, CoMDA-ML produces accurate and generalizable classifications: micro-average ROC curve, AUC = 0.81; and AUC = 0.85 for NC, 0.67 for MCI, and 0.83 for IC. CoMDA and COMDA-ML are reliable and time-sparing tools, accurate in classifying cognitive profile in parkinsonisms.This study has been registered on ClinicalTrials.gov (NCT04858893).

How Cognition and Motivation "Freeze" the Motor Behavior in Parkinson's Disease.

OBJECTIVE: Freezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG. METHODS: Three hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis. RESULTS: FoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoG- patients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively). CONCLUSION: FoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitive-behavioral alterations related to the occurrence of FoG.

Efficacy of intensive multidisciplinary rehabilitation in Parkinson's disease: a randomised controlled study.

OBJECTIVE: To evaluate whether a 4-week multidisciplinary, aerobic, motor-cognitive and intensive rehabilitation treatment (MIRT) improves the quality of life (QoL) of patients with Parkinson's disease (PD), in the short-term and long-term period. METHODS: This is a prospective, parallel-group, single-centre, single-blind, randomised clinical trial (ClinicalTrials.gov NCT02756676). 186 patients with PD, assigned to experimental group, underwent MIRT; conversely, 48 patients, assigned to control group, did not receive rehabilitation. Parkinson's Disease Questionnaire-39 was assessed 2 (T0), 10 (T1) and 18 (T2, only experimental group) weeks after the enrolment. We compared T1 versus T0 scores within subjects and delta scores (T1-T0) between subjects. To investigate the long-term effects, we compared T2 and T0 scores in the experimental group. RESULTS: At T0, no between-group differences in the Global Index Score (GBI) were observed (experimental group: 43.6±21.4, controls: 41.6±22.9, P=0.50). At T1, we did not find significant changes in controls (delta score: 1.2±9.9, P=0.23), and we found an improvement in GBI in the experimental group (delta score: -8.3±18.0, P<0.0001), significant also between subjects (P<0.0001). Comparing T2 versus T0 in the experimental group, the GBI maintained a significant improvement (delta score: -4.8±17.5, P<0.0001). CONCLUSIONS: A rehabilitation treatment such as MIRT could improve QoL in patients with PD in the short-term and long-term period. Even though the single-blind design and the possible role of the placebo effect on the conclusive results must be considered as limitations of this study, the improvement in outcome measure, also maintained after a 3-month follow-up period, suggests the effectiveness of MIRT on the QoL. CLINICAL TRIAL REGISTRATION: NCT02756676: Pre-results.

Italian validation of the Belastungsfragebogen Parkinson kurzversion (BELA-P-k): a disease-specific questionnaire for evaluation of the subjective perception of quality of life in parkinson's disease.

BACKGROUND: Quality of life (QoL) is the sense of well-being perceived by people. The improvement of parkinsonian patient's QoL is a crucial goal for clinicians involved in rehabilitative care. In order to provide an appropriate endpoint for the assessment of the effectiveness of rehabilitation treatments on QoL of patients with Parkinson's Disease (PD), in this study we have first translated and then validated the Belastungsfragebogen Parkinson kurzversion (BELA-P-k). This tool allows evaluating separately two crucial aspects: i) the loss of personal autonomy in activities of daily life and ii) the psychological and psychosocial impact of the disease. METHODS: The BELA-P-k was translated from Dutch into Italian. Subsequently 202 PD patients filled out the questionnaire. Patients were also evaluated by using the Parkinson Disease Questionnaire -39 (PDQ39), the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). RESULTS: The internal consistency for total of two different scores Bothered by (Bb) and Need for Help (NfH) was excellent (p = 0.91) for both categories. The correlation between Bb and NfH categories was significant and strong, very-strong, ranging from 0.78 to 0.88 (all p < 0.0001). Finally, the value of Spearman r for the relationship between Bb and NfH items and PDQ 39 values were significant (p ≤ 0.003). CONCLUSIONS: In conclusion, we validated the BELA-P-k and demonstrated that it is an appropriate and potentially useful tool for assessing QoL in the management of PD. TRIALS REGISTRATION: This trial was retrospectively registered with ClinicalTrials.gov, NCT03073044.

A study on the inactivation of micro-organisms and enzymes by high pressure CO2.

This study addresses some microbial inactivation phenomena induced by high pressure CO2 over micro-organisms and enzymes. The activity of four selected enzymes was measured before and after treatment with CO2 under pressure in both buffer solutions and natural cellular environment (E. coli cells and tomato paste). Results are reported for acid phosphatase, alkaline phosphatase, ATPase, and pectinase at different conditions of temperature, CO2 pressure, and treatment time (32-40 degrees C, 85-150 bar, 30-70 min). The results obtained show that the high pressure CO2 treatment induces an inactivation of cellular enzymatic activity higher than the one caused on the same enzymes in solution. However, the measured activity difference is not caused by a damage at the enzymes molecular level but is a consequence of the permeabilization of the cellular envelopes which leads to a release of unmodified enzymes from the cells with simultaneous drop of enzymatic cellular activity. The reported data suggest that the bacterial cell death is probably due not to a selective effect of high pressure CO2 treatment but to simultaneous detrimental action of CO2 on cellular membrane and cell wall.