Papers by Gabriella Santangelo
Neurological Sciences
The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also including subtests to... more 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 gend...
Parkinsonism & Related Disorders, 2015
Background and objectives: Hearing impairment (HI) has been previously demonstrated in patients w... more Background and objectives: Hearing impairment (HI) has been previously demonstrated in patients with Parkinson's disease (PD). Pure Tone Audiometry (PTA) gives no information about patients' ability to hear and understand speech. To find out hearing ability and speech discrimination of PD patients, we expanded audiological evaluation by means of speech audiometry (SA). Patients and methods: We screened a series of consecutive PD patients. Severity of motor symptoms and staging were measured by the UPDRS-III and the H&Y scales. Audiometric evaluation consisted of a standardized audiological examination, PTA and SA. Healthy age-and sex-matched subjects were selected as controls. Results: 45 PD patients and 45 healthy controls were enrolled. PTA confirmed our previous finding of high-frequency HI in PD patients. The mean values for the Speech Recognition Threshold were higher in PD patients as compared with controls. PD patients were more likely to have impaired speech discrimination profiles and higher disease stages. Neither the patients nor the controls showed a significant speech-tone dissociation and rollover phenomenon. Conclusion: Our results confirmed sensorineural HI in PD patients. Moreover, SA showed impaired speech discrimination abilities in PD patients as compared with control group thus expanding the audiologic findings of PD.
Sleep, Jan 6, 2015
Restless legs syndrome (RLS) has a prevalence of 0% to 52% in Parkinson disease (PD). However, it... more Restless legs syndrome (RLS) has a prevalence of 0% to 52% in Parkinson disease (PD). However, it is still debated whether RLS in PD is a premotor feature, a motor complication, or an association by chance. The present study aims to evaluate RLS prevalence in de novo PD subjects, and incidence during 4-year follow-up, together with laboratory, clinical, and neuroradiological correlates. This is a 4-year longitudinal study, with evaluations at the time of PD diagnosis, and after 2 and 4 years. One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-year follow-ups at the Movement Disorder Unit of Federico II University Hospital, Naples, Italy. Motor features, non-motor symptoms (NMS), concomitant dopaminergic and non-dopaminergic treatments were recorded. At baseline visit, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability. RLS diagnosis was performed with the RLS Dia...
Journal of Neurology, 2013
To explore the neuropsychological and neurobehavioral profile in adult patients affected by nonsy... more To explore the neuropsychological and neurobehavioral profile in adult patients affected by nonsymptomatic (cryptogenic and idiopathic) occipital lobe epilepsy (OLE), with normal intelligence, we enrolled 20 adult patients with nonsymptomatic OLE and 20 age-, sex-, and education-matched healthy subjects. All participants underwent neuropsychiatric assessment scales, and standardized neuropsychological tests tapping memory, executive functions, constructional, visuospatial and visuoperceptual skills. After Bonferroni correction for multiple comparisons, patients performed significantly worse than controls on several tests tapping complex visuospatial skills and frontal lobe functions. The analysis of single patients' performance revealed that a significantly higher number of OLE patients achieved age-and education-adjusted pathological scores on three tests (Benton Judgment of Line Orientation Test, Freehand Copying of Drawings Test, color-word interference task of Stroop test) with respect to controls. Patients did not differ from control subjects on neuropsychiatric aspects. The direct comparison between OLE subtypes showed that cryptogenetic OLE patients tended to achieve lower scores than idiopathic OLE patients on most tests, but no difference between the two groups was fully significant. In summary, patients with nonsymptomatic OLE can be affected by clinically relevant impairments in selected neuropsychological domains: complex visuospatial skills and executive functions. It could be speculated that frontal and visuospatial cognitive deficits might be the result of epileptic activity spreading within a neural network that includes structures far beyond the occipital lobe.
Human Movement Science, 2014
It has been repeatedly demonstrated that mentally performing an action and mentally transforming ... more It has been repeatedly demonstrated that mentally performing an action and mentally transforming body-parts entail simulation of one's own body movements, consistent with predictions of embodied cognition theories. However, the involvement of embodied simulation in mental transformation of whole-body images is still disputed. Here, we assessed own body transformation in Parkinson's disease (PD) patients with symptoms most affecting the left or the right body side. PD patients were required to perform left-right judgments on front-facing or back-facing human figures, and a letter rotation task. Results demonstrated that PD patients were selectively impaired in judging the side of back-facing human figures corresponding to their own most affected side, but performed as well as healthy subjects on mental transformation of front-facing bodies and on letter rotation. These findings demonstrate a parallel impairment between motor and mental simulation mechanisms in PD patients, thus highlighting the specific contribution of embodied cognition to mental transformation of whole-body images.
Neurological Sciences, 2013
The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale ... more The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the Englishlanguage MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be C0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was C0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.
Neurological Sciences, 2012
Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dy... more Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤ 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤ 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (β ≤ -0.16) and age with all FAB items but prehension behavior (β ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (β = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.
PLoS ONE, 2013
Background: The variability in the clinical phenotype of Parkinson's disease seems to suggest the... more Background: The variability in the clinical phenotype of Parkinson's disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and nonmotor symptoms in a large cohort of newly diagnosed untreated PD patients.
Movement Disorders, 2012
Background: Action naming is the capacity to correctly identify and name an action. Although acti... more Background: Action naming is the capacity to correctly identify and name an action. Although action naming has been found to be impaired in a host of neurodegenerative conditions, its neural substrates have been rarely explored.
Journal of Neurology, 2013
Epidermal growth factor (EGF) has been proposed as a candidate biomarker for cognitive impairment... more Epidermal growth factor (EGF) has been proposed as a candidate biomarker for cognitive impairment in Parkinson's disease (PD). We aimed to assess the relationship between serum EGF and cognitive functions in early, drug-naive PD patients and evaluate the predictive value of EGF on cognitive functions in a 2-year follow-up study. Serum EGF was measured in 65 early, drug-naive PD patients, that underwent a comprehensive neuropsychological battery. Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III). Neuropsychological evaluation was repeated after 2 years. Spearman's rank correlation was used to assess the relationship between serum EGF levels and neuropsychological variables. Linear regression analysis was used to evaluate the relationship between EGF and neuropsychological scores as well as other variables (age, gender, UPDRS-III, levodopa equivalent dose, and type of treatment at follow-up) potentially affecting cognitive performance. Variation over time in cognitive scores was analyzed using repeated-measures ANOVA. At baseline, EGF was the only significant variable associated with performance on semantic fluency (R (2) = 0.131; p = 0.005). EGF levels (p = 0.025), together with UPDRS-III (p = 0.009) and age (p = 0.011), were associated with performance on frontal assessment battery (R (2) = 0.260). At 2-year follow-up, EGF was the only significant variable to predict performance on semantic fluency (R (2) = 0.147; p = 0.025) and color naming task of Stroop color-word test (R (2) = 0.121; p = 0.044). Serum EGF levels are related to frontal and temporal cognitive functions in early, drug-naive PD patients and predict performance on frontal and posterior cognitive functions at 2-year follow-up. EGF is proposed as a potential serum biomarker for early cognitive impairment in PD.
Journal of Neurology, 2012
Little is known about the relationship between cognitive dysfunctions and the non-motor complex i... more Little is known about the relationship between cognitive dysfunctions and the non-motor complex in subjects with newly diagnosed untreated Parkinson's disease (PD). The aim of this study was to explore the association between non-motor symptoms (NMS) and cognitive dysfunctions in an incident cohort of de novo, drug-naive, PD patients. Sixty-six non-demented, early, untreated PD patients completed a semi-structured interview on NMS and a battery of neuropsychological tests that assess verbal memory, visuospatial abilities, and attention/executive functions. Scores were age- and education-corrected. Patients who failed at least two tests for each cognitive domain were diagnosed as having mild cognitive impairment (MCI). All but three (95.4%) PD patients complained of at least one NMS. A total of 37.8% was diagnosed with MCI. There was a relationship between sleep-NMS and cognitive dysfunctions. Specifically, both REM behavioral sleep disorders (RBD) and insomnia were associated with lower scores on several cognitive tests. Moreover, RBD was closely related to MCI. NMS and MCI are very common even in the early phase of PD, before patients are treated. Given the correlation between sleep disturbances and cognitive impairment, it is possible that sleep symptoms in PD patients might be considered as an early marker of dementia.
Movement Disorders, 2015
A B S T R AC T : The variability in the clinical phenotype of Parkinson's disease (PD) suggests t... more A B S T R AC T : 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 5 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 5 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 Ldopa 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. V C 2015 International Parkinson and Movement Disorder Society
Journal of Neurology, 2013
Word count paper/abstract: 2.422/226 Number of characters in the title: 113 Number of references/... more Word count paper/abstract: 2.422/226 Number of characters in the title: 113 Number of references/tables: 30/2 Supplementary material: 1 table Abstract Background: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.
Parkinsonism & Related Disorders, 2012
Background: Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). A... more Background: Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and 123 I-FP-CIT as the dopamine transporter ligand. Methods: Thirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right-and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with 123 I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms. Results: Comparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate. Conclusions: We reported an association between nigrostriatal DAT availability deficits and anxiety symptoms in newly diagnosed, untreated PD patients. Our results suggest that hypofunction of the nigrostriatal dopaminergic system may represent one of the functional anomalies involved in anxiety in PD from the earliest stages of disease and irrespective of any therapy.
Journal of Neurology, 2014
Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impai... more 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.
Neurological Sciences, 2012
The aim of the present study was to evaluate the effects of a Global Postural Rehabilitation (GPR... more The aim of the present study was to evaluate the effects of a Global Postural Rehabilitation (GPR) program on motor symptoms and gait parameters of patients with Parkinson's disease (PD) by means of three-dimensional motion analysis study. Ten subjects with clinical diagnosis of PD were enrolled (study group). Age-, sex- and disease duration-matched PD patients were recruited as a control group (no treatment). Three-dimensional motion analysis was conducted by means of a stereophotogrammetric system. After basal evaluation, the study group underwent a specific rehabilitation program consisting of individual 40 min GPR daily sessions, 3 days a week for 4 consecutive weeks. Neurological status and spatiotemporal gait parameters of the two groups were evaluated at study entry (t (0)), at 4 weeks (t (1), end of rehabilitation protocol) and at 8 and 12 weeks (t (2) and t (3), follow-up evaluation). At baseline evaluation, the two groups did not differ in clinical features and gait parameters. At the end of rehabilitation protocol (t (1)) and at follow-up evaluation (t (2) and t (3)), a significant improvement in temporal gait parameters and UPDRS scores was observed in all treated patients as compared to baseline and controls. Our preliminary findings showed that significant improvements in mobility and gait parameters of PD patients can be obtained through GPR treatment, with a parallel improvement in clinical status. Quantitative analysis of gait pattern can be considered a useful tool to assess the efficacy of rehabilitation interventions in patients affected by PD.
Journal of Neurology, 2013
Parkinsonism & Related Disorders, 2013
A relation between the side of motor onset and cognitive impairment in early PD has been reported... more A relation between the side of motor onset and cognitive impairment in early PD has been reported, suggesting that the asymmetric degeneration affecting subcortical regions may play a pivotal role in lateralized cognitive function. However, evidences are controversial and all previous studies were performed on treated patients, though it is known that dopaminergic therapy can affect cognition in PD. Sixty-nine early untreated PD patients underwent an extensive neuropsychological battery exploring memory, visuospatial and attention/executive functions. Patients were divided with respect of the side of onset (right vs. left) and further grouped according to motor phenotype (tremor vs. rigidity-bradykinesia). Multivariate analysis of variance has been carried out to compare clinical and neuropsychological data between subgroups. There were no differences in any neuropsychological task between right-sided and left-sided onset subgroups, irrespective of tremor dominant or rigid-bradykinetic phenotype. Age at onset was significantly higher in patients with any cognitive impairment as compared with patients without (66.7 ± 3.2 vs. 56.3 ± 6.8 years, p = 0.001). Side of motor onset is not a major determinant for developing lateralized cognitive deficits in newly diagnosed untreated PD patients.
Movement Disorders, 2011
... Federica Bombieri MD 3 ,; Gabriella Santangelo PhD 6,7 ,; Marianna Amboni MD 4,5,6 ,; Paolo B... more ... Federica Bombieri MD 3 ,; Gabriella Santangelo PhD 6,7 ,; Marianna Amboni MD 4,5,6 ,; Paolo Barone MD, PhD 5,6 ,; Michele Tinazzi MD, PhD 3. Article first published online: 24 AUG 2011. DOI: 10.1002/mds.23918. ... 4 Università Parthenope, Napoli, Italy. 5 ...
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Papers by Gabriella Santangelo