Katia Longo

Freezing of Gait and Executive Functions in Patients with Parkinson's Disease

Freezing of gait (FOG) is a frequent, disabling symptom of Parkinsons disease (PD). FOG usually lasts a few seconds. It refers to brief paroxysmal events during which a subject is unable to start or continue locomotion. Despite its frequency, FOG pathophysiology is unclear. Because a frontal lobe dysfunction or a disconnection between the frontal lobe and basal ganglia has been implicated in FOG, we explored frontal functions in PD patients using neuropsychological tests. Thirteen early‐stage PD patients [Hoehn & Yahr score (H&Y) ≤ 2.5] with freezing during “on ” state (FOG+), and 15 age‐, H&Y score‐, and disease‐duration‐matched PD patients without freezing (FOG−) were investigated. No patient was demented or depressed. Assessment included the Unified Parkinsons Disease Rating Scale (UPDRS), FOG questionnaire, Mini Mental State Examination (MMSE), frontal assessment battery (FAB), phonemic verbal fluency, Stroop test (parts II and III), and ten‐point clock test (TPCT). UPDRS and MMSE scores did not differ between the two groups. FAB, verbal fluency, and TPCT scores were significantly lower in FOG+ patients than in FOG− patients (FAB: P = 0.008; phonemic verbal fluency: P = 0.011; TPCT: P = 0.024). FOG correlated with lower scores at frontal tests in patients with early‐stage PD.

The heterogeneity of early Parkinson's disease: a cluster analysis on newly diagnosed untreated patients.

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 non-motor symptoms in a large cohort of newly diagnosed untreated PD patients. Methods We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored. Results The data driven approach identified four distinct groups of patients, we have labeled: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant. Conclusion Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.

Relationship between depression and cognitive dysfunctions in Parkinson’s disease without dementia

To explore the relationship between depression and cognitive impairment in non-demented PD patients, we evaluated neurological and neuropsychological asset in 65 patients with a diagnosis of major depressive disorder (dPD) according to DSM-IV criteria and 60 patients without depression (nPD).Compared with nPD patients, dPD patients had significantly higher scores on behavioral rating scales and performed worse on the Frontal Assessment Battery (FAB), Semantic Fluency Task, Copying Task (CT), and Stroop Test. Three dPD subgroups were identified based on the first two DSM-IV criteria: patients fulfilling criterion 1 (depressed mood; group 1); patients fulfilling criterion 2 (apathy/anhedonia; group 2); patients fulfilling criteria 1 and 2 (group 3). Patients of group 2 scored significantly lower than patients of group 1 on the CT, FAB and phonological fluency task. Patients of groups 2 and 3 scored significantly lower than nPD patients on visuoconstructional and frontal tasks. Similar results were obtained in dPD patients stratified in four subgroups based on cut-off scores of the Apathy Evaluation Scale and the Snaith Hamilton Pleasure Scale. In summary, PD patients with concomitant apathy and anhedonia may show more severe cognitive impairments. Since such patients are diagnosed to be affected by depression according to clinical DSM-IV criteria, we suggest that DSM-IV criteria may not distinguish an affective from a cognitive disorder in PD.

Ropinirole as a treatment of restless legs syndrome in patients on chronic hemodialysis: an open randomized crossover trial versus levodopa sustained release.

ObjectiveRestless legs syndrome (RLS) is a common neurologic condition characterized by uncomfortable and unpleasant sensations in the legs, occurring primarily at rest, which are usually worse in the evening and are alleviated by movement. RLS is present in 20–40% of patients with renal failure. This study was a 14-week open, randomized, crossover trial of ropinirole vs. levodopa sustained release (SR) in 11 patients with RLS on chronic hemodialysis. MethodsEleven patients (7 men, 4 women) were enrolled in the study. They received either levodopa SR or ropinirole for 6 weeks, followed by a washout week, then the alternate treatment for 6 weeks. Patients rated the severity of RLS by means of a 6-item questionnaire developed by the International Restless Legs Study Group (6-item IRLS), by the Clinical Global Impression (CGI) scale, and by sleep diaries. ResultsUnder treatment with levodopa SR, 1 patient presented severe vomiting, leading to study discontinuation. The 10 patients who completed the study reported a 33.5% improvement (from 16.7 ± 3.2 to 11.1 ± 4; P < 0.001) of the 6-item IRLS scores during levodopa SR treatment and a 73.5% improvement (from 16.6 ± 2.8 to 4.4 ± 3.8; P < 0.001) during ropinirole treatment. By the end of the study the mean levodopa SR dosage was 190 mg/d and the mean ropinirole dosage was 1.45 mg/d. Ropinirole was superior to levodopa SR in reducing 6-item IRLS scores (P < 0.001) and in increasing sleep time (P < 0.001). The patient CGI scale showed a significant difference favoring ropinirole (P < 0.01). There was no significant carryover or period effect for any outcome measure. Four patients reported a complete reversion of RLS symptoms during ropinirole treatment at doses ranging from 0.25–2 mg/d. ConclusionsThese results suggest that ropinirole is more effective than levodopa SR in the treatment of RLS in patients on chronic hemodialysis.

Non-motor symptoms in early Parkinson's disease: a 2-year follow-up study on previously untreated patients

Background Non-motor symptoms are very common among patients with Parkinsons disease since the earliest stage, but little is known about their progression and their relationship with dopaminergic replacement therapy. Methods We studied non-motor symptoms before and after 2 years from dopaminergic therapy introduction in ninety-one newly diagnosed previously untreated PD patients. Results At baseline, nearly all patients (97.8%) referred at least one non-motor symptom. At follow-up, only few non-motor symptoms significantly changed. Particularly, depression and concentration became less frequent, while weight change significantly increased after introduction of dopamine agonists. Conclusions We reported for the first time a 2-year prospective study on non-motor symptoms before and after starting therapy in newly diagnosed PD patients. Even if non-motor symptoms are very frequent in early stage, they tend to remain stable during the early phase of disease, being only few non-motor symptoms affected from dopaminergic therapy and, specifically, by the use of dopamine agonists.

Health-related quality of life and its determinants in Parkinson’s disease: Results of an Italian cohort study

Parkinsons disease (PD) is a common neurodegenerative disorder with a progressive disabling course. Health-related quality of life (HrQoL) in Italian patients with PD has not been evaluated. The objective of this study was to evaluate HrQol of an Italian cohort of PD patients and to provide a comprehensive analysis of HrQoL determinants. We performed a cross-sectional survey of 70 outpatients with idiopathic PD recruited in the department of Neurology, Napoli University, Italy. Clinical data included the Unified PD Rating Scale (UPDRS), motor and non-motor symptoms. The generic instrument EuroQol (EQ-5D and EQ-VAS) was used to evaluate HrQol. Factors influencing HrQol were assessed by multivariate regression analysis. Severe problems in at least one dimension of the EQ-5D were experienced by 60% of PD patients versus 4.7% in general Italian population. The dimensions most affected were mobility, pain/discomfort and anxiety/depression with only 17.4%, 18.8% and 17.4% of patients, respectively, reporting no problems in these dimensions. The mean EQ-VAS score was 54.20 ± 18.38. Independent determinants of reduced HrQoL were increased UPDRS scores, motor fluctuations, dyskinesias, depression and dementia. PD strongly affects HrQol in Italian patients. The results of this study should be considered in the development of national healthcare programmes aimed at improvement of the HrQoL in Italian patients with PD. In particular, these programmes should concentrate not only on motor but also on non-motor manifestations of PD.

Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism

Objective: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using 18F-fluorodeoxyglucose (FDG) and PET (FDG-PET). Methods: This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping. Results: ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls. Conclusion: MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.

Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients

BACKGROUND Anxiety is a common non-motor symptom among patients with Parkinsons 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 ¹²³I-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 ¹²³I-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.

Diffusion-weighted imaging in multiple system atrophy: A comparison between clinical subtypes†

Multiple system atrophy can be classified into two main types, a Parkinsonian (MSA‐P) and a cerebellar (MSA‐C) variant based on clinical presentation. We obtained diffusion‐weighted magnetic resonance imaging (DWI) in 9 MSA‐P and 12 MSA‐C patients and 11 controls, and correlated DWI changes with disease duration and severity. We found that Trace (D) values in the entire and anterior putamen were significantly higher in MSA‐P than in MSA‐C patients and controls, whereas Trace (D) values in the cerebellum and middle cerebellar peduncle (MCP) were significantly higher in MSA‐C than in MSA‐P patients and controls. Increased disease duration was significantly correlated with increased Trace (D) values in pons of MSA‐P patients, and in cerebellum and MCP of MSA‐C patients. Both UMSARS and UPDRS motor scores positively correlated with entire and posterior putaminal Trace (D) values in MSA‐P patients. The diffusivity changes parallel phenotypical and pathologic differences between MSA‐P and MSA‐C patients, suggesting that DWI is a feasible tool for in vivo evaluation of neurodegeneration in MSA. Based on our findings, Trace (D) measurements in the putamen and pons in MSA‐P patients and in the cerebellum and MCP in MSA‐C patients could serve as quantitative markers for microstructural damage in the course of disease.

Mild Cognitive Impairment in newly diagnosed Parkinson's disease: A longitudinal prospective study

INTRODUCTION In PD, Mild Cognitive Impairment (PD-MCI) occurs since early stages of disease. The aims were to assess presence of PD-MCI in untreated, drug-naive PD patients, and to follow-up the sample over 4 years to ascertain evolution of neurocognitive profile. METHODS Seventy-six patients underwent neuropsychological testing at baseline (T0), and after 2 (T1:n = 62) and 4 years (T2:n = 55). Diagnosis of PD-MCI and PD-associated dementia (PDD) was made according to current consensus criteria. RESULTS PD-MCI occurred in 25/76 patients (32.9%) at baseline, and 4 of them reverted from PD-MCI to Normal Cognition (Reverters), 7 remained stable (Non-Reverters) and 2 developed PDD at T2; 12 patients were lost to the follow-up. Among the 51 patients with normal cognition (PD-CN) at T0, 27 had normal cognition at T2 (5 of them were Reverters with respect to diagnosis at T1), 5 had MCI at T1 and T2 (Non-Reverters), 9 had MCI at T2 only, whereas 1 developed PDD; 9 patients were lost to the follow-up. At baseline, Reverters (n = 9) had younger age at onset and better performance on constructional visuospatial task than Non-Reverters (n = 12). Compared to patients without PD-MCI at all evaluations (n = 19), Reverters had poorer performance on verbal immediate recall and attention tasks and higher level of apathy at T0. Reduced performance on the Stroop Test at baseline predicted PD-MCI at T2. CONCLUSION Executive dysfunctions predicted development of PD-MCI after few years from onset. Reversal from PD-MCI to PD-CN was related to young age at onset and high level of apathy at baseline evaluation.