Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.

BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI). METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses. RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests. CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.

Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms. METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA. RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations. CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.

Validation of the Italian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) in an Italian Parkinson's disease cohort.

INTRODUCTION: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated. METHODS: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication. RESULTS: Subsyndromal ICDs manifestations were observed in 54% of the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and the clinical aspects of PD and dopaminergic medication. CONCLUSION: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD.

Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.

BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients. METHODS: N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33). RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach. DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.

Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.

INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort. MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index. RESULTS: The BDI-II proved to be internally consistent (Cronbach's α = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50. CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.

Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.

BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties. METHODS: A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score. RESULTS: The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80). DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.

A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.

INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status. METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated. RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z = - 2.49; p = 0.013; Cohen dz = 0.691. Higher scores of the TEPS total score, Z = - 2.38; p = 0.025; Cohen dz = 0.621, and LEDD, Z = - 2.63; p = 0.008; Cohen dz = 0.731, were also reported at T1. CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.

Vitamin D as a possible biomarker of mild cognitive impairment in parkinsonians.

INTRODUCTION: Mild Cognitive Impairment in Parkinson's Disease (PD-MCI) is a transitional state between normal cognition and dementia. Cross-sectional studies revealed that low Vitamin D levels were associated with worse performance on cognitive tests in Parkinson's Disease. The present longitudinal study aimed to examine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at baseline and possible development of PD-MCI at 24 and 48 months. MATERIALS AND METHODS: Sixty untreated, de novo PD patients underwent clinical and cognitive evaluations and measurement of serum 25(OH)D at baseline assessment (T0). After 24 (T1) and 48 months (T2), cognitive status (presence or absence of PD-MCI) of PD patients were re-evaluated. RESULTS: Vitamin D insufficiency occurred in 93.3% at T0. At T1, significant differences among patients with PD-MCI at both baseline and follow-up, patients with PD-MCI at follow-up and patients who never developed PD-MCI were found on age, age at onset of PD, and education; no significant difference was found on vitamin D levels at T0. A binary logistic regression analysis showed that a lower level of 25(OH)D at T0 (B= -0.158, Wald= 5.280, p = 0.022, Exp (B)=0.854; CI 95%: 0.746-0.977) and lower education (B= -0.214, Wald= 3.859, p = 0.049, Exp (B)=0.807; CI 95%: 0652-1.000) were predictors of PD-MCI occurrence at T2. DISCUSSION: Our results demonstrated that a lower level of 25(OH)D is conceivable as a biomarker of development of PD-MCI throughout the disease. Early diagnosis of Vitamin D insufficiency and its management might be useful to prevent cognitive decline in PD patients.

The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.

Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.

A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.

INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment. OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment. METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression. RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment. CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.

Theory of mind and joint action in Parkinson's disease.

It has been suggested that the Theory of Mind (ToM) may rely on more basic processes of social cognition, such as action control (e.g., joint action), even if little is known about this relationship. The relationship between ToM and joint action can be studied in patients with Parkinson's disease (PD), because they are characterized not only by a deficit in ToM (and in its cognitive and affective subcomponents) but also by a deficit in the inhibition of competing responses. Sixty PD patients and 60 matched healthy controls (HCs) performed a go/no-go Flanker task in both joint and individual conditions. Cognitive (Advanced Test or AT) and affective (Emotion Attribution Task or EAT) ToM also were measured. Thirty-five PD patients and matched HCs also performed the standard Flanker task, as a control measure. In patients, only individuals with high AT scores exhibited a joint Flanker effect, whereas in HCs the joint effect was found irrespectively of AT score. Patients with low EAT scores showed a greater interference effect than patients with high scores, whereas the opposite pattern was found for HCs. In regression analysis AT and EAT scores predicted the Flanker effect in the joint condition only. In the standard task, both groups showed a Flanker effect. The role of different fronto-striatal circuits, especially in PD patients, could explain the different involvement of cognitive and affective ToM in joint tasks. The Flanker effect is discussed considering the referential coding account and the attention-focus account as possible candidates to explain joint action effects.

Assessment of apathy minimising the effect of motor dysfunctions in Parkinson's disease: a validation study of the dimensional apathy scale.

PURPOSE: Apathy is associated with motor symptoms in Parkinson's disease (PD); therefore, its evaluation could be influenced by motor disability. The Dimensional Apathy Scale (DAS) evaluates apathy excluding confounding effects of motor symptoms. The present study had three major aims: (a) to explore the psychometric properties of the DAS in non-demented PD patients; (b) to determine an optimal cut-off score of the DAS to identify apathetic PD patients; and (c) to determine a specific apathy profile in PD patients as compared to healthy controls (HC). METHODS: One hundred and seven PD patients and 100 HC completed the DAS. To explore convergent and divergent validity of the DAS in PD, patients underwent the Apathy Evaluation Scale and tools for assessing depressive symptoms, anxiety and cognition. Clinical aspects were recorded. Receiver operating characteristic curve analyses were carried out to estimate the optimal cut-off score to identify clinically significant apathy. RESULTS: The DAS scores showed high internal consistency and good evidence for convergent and discriminant validity. Maximum discrimination between apathetic and non-apathetic patients was obtained with a cut-off score of 28.5 (total score range: 0-72 with higher score indicating more severe apathy). Comparison between PD and HC groups revealed significant differences on total DAS, behavioural/cognitive initiation and emotional subscales. CONCLUSIONS: The DAS is a valid and reliable tool to assess multidimensional apathy in PD, independently of severity of motor symptoms. Reduced initiation of thought and behaviour and emotional blunting characterised PD patients, without confounding effects of motor disability.

The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals.

The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson's disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30-79 years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.

Serum uric acid is associated with apathy in early, drug-naïve Parkinson's disease.

Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

Lower serum uric acid is associated with mild cognitive impairment in early Parkinson's disease: a 4-year follow-up study.

Cognitive deficits are common in Parkinson's disease (PD) and many patients eventually develop dementia; however, its occurrence is unpredictable. Serum uric acid (UA) has been proposed as a biomarker of PD, both in the preclinical and clinical phase of the disease. The aim of this pilot study was to evaluate relationships between baseline serum UA levels and occurrence of mild cognitive impairment (MCI) at 4-year follow-up in a cohort of early PD patients. Early PD patients, not presenting concomitant diseases, cognitive impairment or treatment possibly interfering with UA levels, underwent neuropsychological testing at baseline and 4-year follow-up. UA levels were determined in serum at baseline. MCI was found in 23 out of 42 PD patients completing 4-year follow-up. Patients presenting MCI had significantly higher age at onset and lower Frontal Assessment Battery scores at baseline as compared with patients cognitively intact. Logistic regression analysis showed that both serum UA levels (OR = 0.54, p = 0.044) and age (OR = 1.16, p = 0.009) contribute to the occurrence of MCI at 4-year follow-up. Our pilot study suggests that lower levels of serum UA in the early disease stages are associated to the later occurrence of MCI. These results need to be confirmed by further studies on larger samples.

Neuropsychological correlates of Pisa syndrome in patients with Parkinson's disease.

BACKGROUND: A complex relationship exists between postural control and cognition in the elderly. Namely, neural mechanisms that are required for the regulation of posture have been variably associated with cognitive dysfunctions. Parkinson's disease (PD) is the second most common neurodegenerative disease among the elderly, and it has been associated with both cognitive and postural abnormalities such as Pisa syndrome (PS). Although its onset has been considered to be multifactorial, the pathophysiological mechanisms underpinning PS are still not fully explained. Until now, no study investigated the possible contribution of cognitive dysfunction to occurrence of PS in PD. PATIENTS AND METHODS: Twenty PD patients with PS and 20 PD patients without PS were enrolled. All patients with PD underwent neuropsychological battery to assess behavioural disturbances, memory, attention, frontal/executive and visuospatial functions. RESULTS: The two groups did not differ on demographic features, age at PD onset and disease duration, whereas they significantly differed on UPDRS-Part III, and levodopa-equivalent daily dose (LEDD). MANCOVA with above-mentioned clinical variable as covariates revealed significant differences on tasks tapping verbal long-term memory, and attentional and visuoperceptual abilities between groups. The binary logistic regression revealed that higher LEDD and lower performance on visuospatial task (Benton Judgment of Lines Orientation test) significantly predicted occurrence of PS. CONCLUSION: Our results revealed a significant association of PS with altered attention and visuoperceptual functions in PD, suggesting that the occurrence of PS may be associated with alteration of both frontal-striatal systems and posterior cortical areas.

Effects of Global Postural Reeducation on gait kinematics in parkinsonian patients: a pilot randomized three-dimensional motion analysis study.

The Global Postural Reeducation (GPR) method is a physical therapy based on the stretching of antigravity muscle chains with the parallel enhancement of the basal tone of antagonistic muscles addressed to improve static and dynamic stability. Through a three-dimensional motion analysis (3DMA) system, our study aims to investigate whether in Parkinson's disease (PD) patients a GPR program results in a more physiological gait pattern. The kinematic parameters of gait of twenty subjects with clinically diagnosed PD were calculated. The patients were randomly assigned to a study (10 or control (10) group. All subjects underwent neurological and 3DMA assessments at entry time (t 0), at 4 weeks (t 1, end of GPR program), and at 8 and 12 weeks (t 2 and t 3, follow-up evaluation). The study group underwent a four-week GPR program, three times a week, for 40 min individual sessions. Kinematic gait parameters of thigh (T), knee (K) and ankle (A) and UPDRS-III scores were evaluated. At the end of the GPR program, we observed an improvement of the kinematic gait pattern, documented by the increase in KΔc and TΔc values that respectively express the flexion amplitude of knee and thigh. The amelioration was persistent at follow-up assessments, with a parallel enhancement in clinical parameters. GPR intervention shows a long-term efficacy on gait pattern in PD patients. Furthermore, we validated 3DMA as a valuable tool to study the kinematics of gait thus refining the understanding of the effects of specific rehabilitation programs.

Nonmotor predictors for levodopa requirement in de novo patients with Parkinson's disease.

The variability in the clinical phenotype of Parkinson's disease (PD) suggests the existence of several subtypes of the disease. Motor heterogeneity of PD is well established, but not nonmotor heterogeneity. At present, we are unable to predict the rate of progression of PD based on robust biomarkers. We aimed to examine the heterogeneity of PD by attempting to identify nonmotor factors associated with the rate of motor progression and functional decline, as measured by the time to reach the need for levodopa therapy during the first 4 years from diagnosis in a cohort of de novo PD patients. The median time to introduction of L-dopa for patients with urinary symptoms was significantly shorter than that for those without (20 vs. 37 months; P = 0.001). Cox's regression models showed that the urinary domain was associated with a higher probability of starting L-dopa (hazard ratio: 2.1; P = 0.002). There was no influence of such confounders as sex, age, baseline motor features, use of dopamine agonists and/or monoamine oxidase B inhibitors, and total L-dopa equivalent daily dosage. Patients with urinary symptoms had higher baseline and follow-up motor and nonmotor disturbances than those without. Our study suggests the existence of a subgroup of patients who show urinary symptoms along with an overall higher motor and nonmotor burden. Such patients are prone to manifest a rapid functional decline over the first 4 years of the disease. Urinary symptoms might be a clinical marker of severity as well as a possible nonmotor subtype of PD.