Paolo Barone

Università degli Studi di Salerno, Fisciano, Campania, Italy

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Publications (296)1276.4 Total impact

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    ABSTRACT: The amount of sun exposure in early life and consequent vitamin D3 level may influence the risk of developing Parkinson's disease (PD). Yet few studies have previously investigated birth trends in PD related to a possible seasonality and sun exposure. The aim of this study was to investigate a possible relationship between PD risk and sun exposure looking at seasonal birth variation of PD subjects in the homogenous geographic area of Naples, Italy. We selected 898 PD subjects and matched with 1796 controls. McNemar's test with Bonferroni correction and autocorrelation were used to test seasonality in birth trends. No difference was found for the month and season of birth between PD subjects and controls. We found a 3.3 % increase of PD female subjects born in September (3.3 %) and 4.1 % increase of PD male subjects born in spring comparing to controls but were not significant after Bonferroni correction. This study evaluated for the first time the seasonal birth trends in relation to PD risk in a Southern European population. We found no association between seasonal birth variations and risk of PD.
    Neurological Sciences 03/2015; DOI:10.1007/s10072-015-2183-4 · 1.50 Impact Factor
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    ABSTRACT: Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO-bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression. A cross-sectional case-control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug-naïve PD subjects and controls. Afterwards, PD subjects were included in a 2-year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels. Seventy-five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2-year follow-up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa-equivalent daily dosage (P = 0.012) were found. Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD. © 2015 EAN.
    European Journal of Neurology 03/2015; DOI:10.1111/ene.12688 · 3.85 Impact Factor
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    ABSTRACT: This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD). Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS. Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy. Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P < 0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P < 0.001) and apathy (P < 0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P = 0.51). Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 03/2015; DOI:10.1002/mds.26170 · 5.63 Impact Factor
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    ABSTRACT: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 02/2015; DOI:10.1016/j.parkreldis.2015.02.015 · 4.13 Impact Factor
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    ABSTRACT: 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. © 2015 International Parkinson and Movement Disorder Society
    Movement Disorders 02/2015; 30(3). DOI:10.1002/mds.26076 · 5.63 Impact Factor
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    ABSTRACT: Mild cognitive impairment (MCI) is a common feature in Parkinson's disease (PD). We performed an exploratory study to investigate dopaminergic nigrostriatal innervation and its cognitive correlates in early untreated PD patients with MCI as compared to cognitively intact patients. A consecutive series of 34-de-novo, drug-naïve patients with PD were enrolled. They underwent [123-I] FP-CIT SPECT and comprehensive neuropsychological battery. MCI was identified in 15 of 34 patients with PD. The two groups did not show any statistically significant difference in age, sex, disease duration, education, lateralization, and H&Y and Hospital Anxiety and Depression Scale scores. Logistic regression analysis showed that UPDRS-III was weakly associated with MCI (P = 0.034). Partial correlation analysis controlling for UPDRS-III and age suggested that in PD patients with MCI reduced V3″ values in the more affected caudate were correlated with reduced performances in frontal assessment battery, Trail Making Test: part B minus Part A and copy task of the Rey-Osterrieth complex figure test. Reduced V3″ values in the more and less affected putamen were significantly related with reduced performance in frontal assessment battery and in copy task of Rey-Osterrieth complex figure test, respectively. No correlation was found between neuropsychological scores and DAT availability in PD patients without MCI. Although preliminary, our results suggest that striatal dopamine depletion may contribute to some cognitive deficit in early never treated PD patients with MCI. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Acta Neurologica Scandinavica 02/2015; DOI:10.1111/ane.12365 · 2.44 Impact Factor
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    ABSTRACT: Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7-58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of the Neurological Sciences 01/2015; DOI:10.1016/j.jns.2015.01.025 · 2.26 Impact Factor
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    ABSTRACT: Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena. Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO. Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%, ) and the WOQ-19 analysis (72.5% versus 64.0%, ). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men. Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect
    The Scientific World Journal 01/2015; 2015. DOI:10.1155/2015/787451 · 1.22 Impact Factor
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    ABSTRACT: To assess over a period of 9 months in a sample of Italian Parkinson’s disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients’ causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3 months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist’s and patient’s perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 % of the patients, while only 36 % of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap.
    Neurological Sciences 01/2015; DOI:10.1007/s10072-014-2060-6 · 1.50 Impact Factor
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    The Journal of neuropsychiatry and clinical neurosciences 01/2015; 27(1):e78-9. DOI:10.1176/appi.neuropsych.13120375 · 2.34 Impact Factor
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    ABSTRACT: Epidemiological studies report a 60-70% reduced risk of Parkinson’s disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated.
    Parkinsonism & Related Disorders 12/2014; 21(3). DOI:10.1016/j.parkreldis.2014.12.008 · 4.13 Impact Factor
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    The Lancet Neurology 12/2014; · 21.82 Impact Factor
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    ABSTRACT: Despite the emphasis on the motor phenotype of Parkinson's disease (PD), it has been increasingly recognized that PD patients experience several nonmotor symptoms (NMS), which have even greater significance when assessed by quality-of-life measures and institutionaliza-tion rates. The burden of NMS tends to increase with age and disease severity and, in the very advanced stage of disease, NMS such as urinary problems, drooling, somnolence, psychosis, and dementia dominate the clinical phenotype. Moreover, the dopaminergic treatment used for the motor symptoms of PD can arise or worsen a number of NMS, including orthostatic hypotension, nausea, sleep disturbances, hallucinations, or impulsive compulsive behaviors. Here we review the most common NMS of PD with a focus on their pharmacological management.
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    ABSTRACT: Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Teva Pharmaceutical Industries and H Lundbeck A/S. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 12/2014; 14(2). DOI:10.1016/S1474-4422(14)70288-1 · 21.82 Impact Factor
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    ABSTRACT: Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes.
    Journal of Neurology 11/2014; 262(2). DOI:10.1007/s00415-014-7591-5 · 3.84 Impact Factor
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    ABSTRACT: The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also including subtests to assess frontal functions such as set-shifting, abstraction and cognitive flexibility. MoCA seems to be useful to identify non-amnestic mild cognitive impairment (MCI) and subcortical dementia; it has high sensitivity and specificity in distinguishing MCI from mild Alzheimer's Disease. Previous studies revealed that certain items of MoCA may be culturally biased and highlighted the need for population-based norms for the MoCA. The aim of present study was to collect normative values in a sample of Italian healthy subjects. Four hundred and fifteen Italian healthy subjects (252 women and 163 men) of different ages (age range 21-95 years) and educational level (from primary to university) underwent MoCA and Mini Mental State Examination (MMSE). Multiple linear regression analysis revealed that age and education significantly influenced performance on MoCA. No significant effect of gender was found. From the derived linear equation, a correction grid for MoCA raw scores was built. Inferential cut-off score, estimated using a non-parametric technique, is 15.5 and equivalent scores were computed. Correlation analysis showed a significant but weak correlation between MoCA adjusted scores with MMSE adjusted scores (r = 0.43, p < 0.001). The present study provided normative data for the MoCA in an Italian population useful for both clinical and research purposes.
    Neurological Sciences 11/2014; DOI:10.1007/s10072-014-1995-y · 1.50 Impact Factor
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    ABSTRACT: Szewczyk-Krolikowski and colleagues recently investigated the influence of age and gender on motor and non-motor features in early Parkinson's disease. We recently published the results of a study specifically designed to assess gender differences in the spectrum of non-motor features in a large number of early, drug-naïve PD patients compared to an age- and sex-matched healthy control group. This letter briefly outlines comparisons between Szewczyk-Krolikowski and colleagues results and ours on this topic
    Parkinsonism & Related Disorders 11/2014; DOI:10.1016/j.parkreldis.2014.03.014 · 4.13 Impact Factor
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    ABSTRACT: Background Diagnosing Parkinson's disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations.Aims of the studyWe aimed to investigate the relationship between serum UA levels and DaT availability in newly diagnosed, drug-naïve PD patients, by means of semiquantitative [(123) I]FP-CIT-SPECT.Methods We recruited 52 newly diagnosed, drug-naïve PD patients, and performed serum UA dosage and [(123) I]FP-CIT-SPECT.ResultsPearson's correlation analysis showed that UA levels were significantly higher in patients with higher averaged, ipsilateral and contralateral DaT binding in caudate, putamen, and striatum.Conclusions We showed, for the first time, by regional semiquantitative analysis of DaT binding in PD patients that UA levels significantly correlates with the severity of dopaminergic impairment in caudate, putamen, and striatum. This study broadens our knowledge on the importance of UA as a biomarker of PD.
    Acta Neurologica Scandinavica 10/2014; DOI:10.1111/ane.12295 · 2.44 Impact Factor

Publication Stats

6k Citations
1,276.40 Total Impact Points

Institutions

  • 2011–2015
    • Università degli Studi di Salerno
      • Department of Medicine and Surgery
      Fisciano, Campania, Italy
    • University College London
      • Institute of Neurology
      London, ENG, United Kingdom
  • 1994–2015
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
  • 2002–2013
    • Erasmus MC
      • Department of Clinical Genetics
      Rotterdam, South Holland, Netherlands
  • 2010
    • University of Catania
      Catania, Sicily, Italy
  • 1983–2010
    • Second University of Naples
      Caserta, Campania, Italy
  • 2009
    • Policlinico Federico II di Napoli
      Napoli, Campania, Italy
    • Naples Eastern University
      Napoli, Campania, Italy
  • 2007
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2006
    • Universita' degli Studi "Magna Græcia" di Catanzaro
      Catanzaro, Calabria, Italy
  • 2005
    • National Research Council
      • Institute of Biostructure and Bioimaging IBB
      Roma, Latium, Italy
  • 2001
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
  • 1984–1989
    • National Institutes of Health
      • Branch of Experiemental Therapeutics
      Maryland, United States