Carmine Vitale

Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease.

ABSTRACT Objective: Using resting-state (RS) fMRI, we investigated the functional integrity of the default-mode network (DMN) in cognitively unimpaired patients with Parkinson disease (PD). Methods: RS fMRI at 3 T was collected in 16 cognitively unimpaired patients with PD and 16 age- and gender-matched healthy controls. Single-subject and group-level independent component analysis was used to investigate differences in functional connectivity within the DMN in patients with PD and healthy controls. Statistical analysis was performed using BrainVoyager QX. In addition, we used voxel-based morphometry to test whether between-group differences in RS functional connectivity were related to structural abnormalities. Results: Patients with PD compared with controls showed a decreased functional connectivity of the right medial temporal lobe and bilateral inferior parietal cortex within the DMN. Although patients with PD were cognitively unimpaired, the decreased DMN connectivity significantly correlated with cognitive parameters but not with disease duration, motor impairment, or levodopa therapy. The analysis of regional volume differences did not reveal any differences in local gray matter between patients and controls. Conclusions: Our findings revealed a functional disruption of the DMN in cognitively unimpaired patients with PD, in the absence of significant structural differences between patients and controls. We hypothesize that a dysfunction of the DMN connectivity may have a role in the development of cognitive decline in PD.

Unawareness of dyskinesias in Parkinson's and Huntington's diseases.

Abstract We performed a clinical study to evaluate the unawareness of dyskinesias in patients affected by Parkinsons disease (PD) and Huntingtons disease (HD). Thirteen PD patients with levodopa-induced dyskinesias and 9 HD patients were enrolled. Patients were asked to evaluate the presence of dyskinesias while performing specific motor tasks. The Abnormal Involuntary Movement Scale (AIMS) and Goetz dyskinesia rating scale were administered to determine the severity of dyskinesias. The Unified Parkinsons disease rating scale (UPDRS) and Unified Huntingtons Disease Rating Scale (UHDRS) were used in PD and HD patients, respectively. In PD we found a significant negative relationship between unawareness score at hand pronation-supination and AIMS score for upper limbs. In HD we found a significant positive relationship between total unawareness score and disease duration. In PD the unawareness seems to be inversely related with severity of dyskinesias, while in HD it is directly related to disease duration and severity.

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.

Functional involvement of central cholinergic circuits and visual hallucinations in Parkinson's disease

Visual hallucinations (VHs) represent a frequent and disturbing complication of Parkinsons disease. Evidence suggests that VH can be related to central cholinergic dysfunction. Short-latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. This inhibition of motor-evoked potentials can be observed when transcranial magnetic stimulation is delivered with a delay ranging from 2 to 8 ms, after a peripheral nerve afferent input has reached the somatosensory cortex. We applied SAI technique in 10 non-demented patients with Parkinsons disease with VHs, in 12 non-demented patients with Parkinsons disease without VHs (NVH-pts) and in 11 age-matched normal controls. All patients with Parkinsons disease underwent a battery of neuropsychological tests to assess frontal and visuospatial functions, memory and attention. SAI was significantly reduced in patients with VHs compared with controls and patients without VHs. Neuropsychological examination showed a mild cognitive impairment in 16 out of 22 patients with Parkinsons disease. In addition, we found that in our patients with VHs, performance of some tasks evaluating visuospatial functions and attentional/frontal lobe functions was significantly more impaired than in patients without VHs. SAI abnormalities, presence of VH and neuropsychological results strongly support the hypothesis of cholinergic dysfunction in some patients with Parkinsons disease, who will probably develop a dementia. A follow-up study of our patients is required to verify whether SAI abnormalities can predict a future severe cognitive decline. Moreover, SAI can also be very useful to follow-up the efficacy of anti-cholinesterase therapies.

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.

Comparative neuropsychological profile of pathological gambling, hypersexuality, and compulsive eating in Parkinson's disease

Background: Impulse control disorders (ICDs), in particular pathological gambling, hypersexuality, and compulsive eating, are being increasingly identified in Parkinsons disease (PD) patients. Pathological gambling has been associated with frontal/executive dysfunctions, whereas hypersexuality and compulsive eating, and their relation with cognitive dysfunctions, have not been investigated in PD.

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.

Cognitive dysfunctions and pathological gambling in patients with Parkinson's disease†

The purpose of this study was to investigate the neuropsychological correlates of pathological gambling (PG) in Parkinsons disease (PD). Fifteen patients with PD affected by PG (identified based on DSM‐IV criteria; PD+PG) without clinically evident dementia were compared with 15 nondemented patients with PD not affected by PG (PD−PG). Two groups of patients with PD were matched for age, length of education, and gender. Clinical and neuropsychiatric features were assessed; several cognitive domains, mainly related to executive functions, were explored by means of standardized neuropsychological tasks. PD+PG and PD−PG did not differ on clinical and neuropsychiatric aspects. PD+PG patients performed significantly worse than PD−PG patients on cognitive tasks that evaluated visuo‐spatial long‐term memory and several frontal lobe functions. After Bonferroni correction, differences remained significant on the Frontal Assessment Battery (FAB) (P = 0.001), on phonological fluency task (P = 0.003), and on the Trail Making Test, part B minus part A (P = 0.002). Logistic regression analysis demonstrated that low scores on the FAB were the only independent predictor of PG (odds ratio, 27.9; 95% CI: 2.82–277.95, P = 0.004). The results indicate an association between PG and frontal lobe dysfunctions in nondemented patients with PD. Low scores on the FAB indicate patients with PD at high risk for PG.

A neuropsychological longitudinal study in Parkinson's patients with and without hallucinations

The aim of this work was to determine the progression of cognitive impairment in Parkinsons disease (PD) patients with or without hallucinations. Two years after the first assessment, 36 PD patients were re‐evaluated on standardized neuropsychological tests, including the Frontal Assessment Battery (FAB), and on rating scales for overall cognitive functioning, functional autonomy, behavioral disorders. Nine patients had hallucinations at baseline and endpoint assessments; 12 patients developed hallucinations during the follow‐up; and 15 patients were hallucination‐free throughout the study. Cognitive performance significantly declined in all three groups, but at endpoint assessment PD hallucinators scored significantly lower than nonhallucinators on phonological and semantic fluency tasks, immediate free recall and the go/no‐go FAB subtest; moreover, they showed more severe apathy than nonhallucinators. Reduced phonological fluency at baseline (odds ratio [OR], 13.5; 95% CI: 1.34–135.98, P = 0.027) was the only independent predictor of onset of hallucinations after 2 years, whereas hallucinations (OR, 10.1; 95% CI: 1.94–51.54, P = 0.006) and poor phonological fluency (OR, 6.1; 95% CI: 1.04–35.03, P = 0.045) independently predicted development of diffuse cognitive impairment. We concluded that reduced verbal fluency scores may predict the onset of hallucinations, while hallucinations and poor phonological fluency may predict development of dementia in PD patients.