Motor and non-motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel: final results of the GREENFIELD observational study.

INTRODUCTION: The GREENFIELD observational study assessed the effect of levodopa/carbidopa intestinal gel (LCIG) on motor and non-motor symptoms, and the related impact on patient quality of life and caregiver burden up to 8 years. METHODS: Final results of a large Italian cohort of patients who started LCIG in routine care between 2007 and 2014 are presented. Comparison between baseline (before LCIG) and follow-up visits on yearly basis (visit 2/3) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS-IV) Item 39; secondary endpoints were UPDRS I and II, dyskinesia items, PD Quality of Life Questionnaire-39, Parkinson's Disease Sleep Scale-2, Gait and Falls Questionnaire, Questionnaire on Impulsive Disorders, and Relative Stress Scale. RESULTS: Overall, 145 patients from 14 centers were assessed with a mean time since LCIG start of 2.8 ± 1.7 years at visit 2. The mean UPDRS-IV item 39 score showed significant reductions compared to baseline (mean score 2.0 ± 0.81) at visit 2 (mean score 0.9 ± 0.69; - 55%; p < 0.001) and at visit 3 (mean score 1.0 ± 0.75; - 50%; p < 0.001). At visit 3, significant reductions were observed for dyskinesia duration score (- 28%; p < 0.001), dyskinesia disability (- 40%; p < 0.001), and painful dyskinesia (- 50%; p < 0.001). Overall, 40 (27.6%) patients experienced 49 serious adverse events which were considered related to PEG/J procedure or to device in 16.3% of the cases. CONCLUSIONS: The results of this study support the long-term efficacy of LCIG on PD symptoms as well as on activities of daily living. The adverse events were consistent with the established LCIG safety profile.

DAT gene polymorphisms (rs28363170, rs393795) and levodopa-induced dyskinesias in Parkinson's disease.

L-dopa-induced dyskinesias (LID) is a common motor side effect of levodopa therapy of Parkinson's disease (PD). The identified predictors may only partially account for the risk of developing LID and genetic factors may contribute to this variability. The present study is aimed to investigate whether polymorphisms in the dopamine transporter gene (DAT) are associated with the risk of developing LID. Genotyping of the 40-bp VNTR (rs28363170) and rs393795 (A/C) polymorphisms of the DAT gene was performed in a well-characterized cohort of 181 Italian PD patients in treatment with L-DOPA for 3 years or more. The results of our study show that there is no difference in dyskinesias prevalence among carriers of the two DAT gene polymorphisms. However, the combination of the two genotypes 10R/10R (rs28363170) and A carrier (rs393795) of the DAT gene reduces the risk of LID occurrence during long-term therapy with l-DOPA with respect to the PD subjects who did not carry these alleles (OR = 0.31; 95% CI, 0.09-0.88). Also based on a logistic regression analysis, the 10R/10R and the A carrier allele of the rs393795 polymorphisms of the DAT gene, could reduce the susceptibility to develop LID during levodopa therapy adjusted by demographical and clinical variables (OR = 0.19; 95% CI, 0.05-0.69). Additional studies further investigating the rs28363170 and rs393795 polymorphisms with LID in PD are needed to clarify their role in different ethnicities.

Cardiovascular dysfunction in untreated Parkinson's disease: A multi-modality assessment.

BACKGROUND: The clinical presentation of Parkinson's disease (PD) includes a wide spectrum of non-motor features, including cardiovascular autonomic failure. OBJECTIVE: To evaluate cardiovascular autonomic status and cardiac functional capacity in drug-naïve PD patients. METHODS: 18 newly-diagnosed PD patients underwent laboratory cardiovascular autonomic function tests using power spectral analysis of the R-R interval, blood pressure (BP) short-term variability and non-invasive baroreflex sensitivity (BRS). A two-dimensional (2D) transthoracic echocardiogram, spirometry and cardiopulmonary exercise test (CPET) were also performed. Thirteen patients underwent myocardial scintigraphy with [123I] metaiodobenzylguanidine (MIBG). RESULTS: At rest, total power spectral analysis of heart rate variability was lower in PD patients than in controls. BRS decreased during sympathetic activation in both patients and controls. While echocardiography and spirometry were normal, a mild degree of exercise intolerance was observed at the CPET in PD patients (mean V'O2max: 83% of predicted; mean Wmax: 80% of predicted). The heart-to-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired in 9 patients, one of whom displayed a definite cardiovascular dysautonomic pattern. CONCLUSIONS: Our results confirm that subclinical to overt cardiovascular autonomic failure may occur from the early stages of PD. The less efficient adaptive response to physical stimuli during the CPET and postural changes observed in untreated PD patients possibly reflect cardiac sympathetic denervation, although the involvement of PD-related motor impairment in physical deconditioning cannot be excluded.

Motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study.

Several levodopa/carbidopa intestinal gel (LCIG) studies showed a significant reduction of OFF time and a significant increase of ON time, as well as a reduction of dyskinesia, and improvement of non-motor symptoms and quality of life. However, few studies have been conducted in a large population for more than 3 years. Interim outcomes from GREENFIELD observational study on a large Italian cohort of advanced PD patients who started LCIG in routine care between 2007 and 2014, still on treatment at the enrollment, are presented. Comparison between baseline (before LCIG start) and visit 1 (at enrollment) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS) IV Item 39; secondary endpoints were UPDRS I and II, as outcome of quality of life. Overall, 145 of 148 enrolled patients from 14 Movement Disorder Centers in Italy were evaluable with a mean LCIG treatment period of 1.38 ± 1.66 years at enrollment. Compared with baseline, the mean score regarding daily time spent in OFF (UPDRS IV Item 39) at visit 1 significantly decreased from 2.1 ± 0.8 to 0.9 ± 0.7 (57 % reduction vs baseline, P < 0.0001); UPDRS IV improved by 39 % (P < 0.0001); scores for dyskinesia duration and disability were reduced by 28 % (1.8 ± 1.0-1.3 ± 0.9; P < 0.0001) and 33 % (1.5 ± 1.1 to 1.0 ± 1.0; P < 0.0001), respectively; and the scores for painful dyskinesia and early morning dystonia were reduced by 56 % (0.9 ± 1.0-0.4 ± 0.7; P < 0.0001) and 25 % (0.4 ± 0.5-0.3 ± 0.5; P < 0.001), respectively. The preliminary results of this interim analysis support the efficacy of LCIG on motor complications and activities of daily living.

Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ(2) = 9.9; OR, 1.7; 95% CI, 1.2-2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ(2) = 13.6; OR, 2.03; 95% CI, 1.4-3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3-6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

Is cognitive stability in Parkinson's disease a predictable phenomenon? A 5-year follow-up study.

Cognitive disturbances are integral to the course of PD but the rate of cognitive decline remains largely unpredictable. The aim of this study was to determine the clinical features associated with "cognitive stability". Fifty-four patients (32 with normal cognition and 22 featuring MCI) were recruited in 2009 and re-evaluated after a mean time of 4.7 years; all patients underwent a detailed neuropsychological and clinical evaluation. A proportion of 61 % of patients (19 with normal cognition and 14 with MCI) remained cognitive stable, whereas 39 % had reduced cognitive reserve. After multivariate analysis, only the preservation of visuo-spatial domain was predictive of cognitive stability.

Does a volume reduction of the parietal lobe contribute to freezing of gait in Parkinson's disease?

BACKGROUND: Freezing of gait (FOG) is as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. Structural neuroimaging studies on FOG in PD using volumetric techniques yielded variable and partially conflicting findings, probably reflecting the heterogeneity and complexity of the phenomenon. The aim of this study was to further explore the differences in local gray matter (GM) volume in patients with PD with and without FOG by using Voxel-Based Morphometry (VBM). MATERIALS AND METHODS: We enrolled 26 patients (7 women and 19 men) with a diagnosis of PD in stable treatment with dopaminergic therapy. Thirteen patients classified as FOG+ were matched with thirteen non-freezer (FOG-) PD patients. All 26 participants underwent a detailed neuropsychological assessment as well as a VBM analysis derived from T1 weighted 3T MRI. RESULTS: The patient groups did not significantly differ for age, disease duration, H&Y stage, UPDRS part-III or educational attainment. No significant differences of cognitive profile emerged. PD-FOG+ patients showed a pattern of relative GM atrophy in left posterior parietal gyrus compared with PD-FOG-. DISCUSSION: Our results suggest that a specific pattern of cortical volume reduction involving posterior parietal cortex contributes to the occurrence of FOG in PD. These data agree with the growing body of evidence considering the parietal posterior cortex as an associative area involved in spatial control of motor behavior, par-taking in response selection to sensory evaluation.

Reversible Pisa syndrome associated to subdural haematoma: case-report.

BACKGROUND: Pisa Syndrome or Pleurothotonus is a relatively rare truncal dystonia, characterized by tonic flexion of the trunk and head to one side with slight rotation of the body. Since frequently associated to specific drugs such as antipsychotics and cholinesterase inhibitors or to Parkinson Disease, a pathophysiological role of cholinergic-dopaminergic imbalance has been suggested. We report here the first case of Pisa Syndrome due to an extracerebral pathology as subdural haematoma. CASE PRESENTATION: A hypertensive patient was admitted to Our Department for subacute onset of tonic flexion and slight rotation of the trunk associated to progressive motor deficit in left upper limb after a mild head trauma without loss of consciousness occurred around three month before. No previous or current pharmacological interventions with antidepressant, neuroleptic or anticholinergic drugs were anamnestically retrieved. Familiar and personal history was negative for neurological disorders other than acute cerebrovascular diseases. Acutely performed cerebral MRI with DWI showed a voluminous right subdural haematoma with mild shift of median line. After surgical evacuation, both motor deficit and truncal dystonia were dramatically resolved. At one-year follow up, the patient did not develop any extrapyramidal and cognitive signs or symptoms. CONCLUSIONS: According to many Authors, the occurrence of truncal dystonia during several pharmacologic treatments and neurodegenerative disorders (such as Alzheimer disease and parkinsonian syndromes) supported the hypothesis that a complex dysregulation of multiple neurotransmitter systems are involved. We suggest a possible role of basal ganglia compression in pathogenesis of truncal dystonia by means of thalamo-cortical trait functional disruption and loss of proprioceptive integration. A further contribution of the subcortical structure displacement that alters motor cortex connectivity to basal ganglia may be postulated.

Clinical subtypes in Parkinson's disease: the impact of MAPT haplotypes.

The H1 haplotype of the MAPT gene influences the risk of PD and has been related to the development of PDD. We evaluated the influence of MAPT haplotypes on the expression of motor features in PD patients. We genotyped, for the MAPT haplotypes H1 and H2, a sample of 181 PD patients with distinct clinical subtypes: tremor dominant and non-tremor dominant (NTD). Our results indicate that the MAPT haplotypes contribute to the expression of motor features of PD. H1 homozygous PD patients are significantly more likely to present a NTD phenotype, a clinical subtype characterized by widespread pathological degeneration, than H2 carriers.

Depressive symptoms in Parkinson's disease and in non-neurological medical illnesses.

BACKGROUND: Patients with neurological and non-neurological medical illnesses very often complain of depressive symptoms that are associated with cognitive and functional impairments. We compared the profile of depressive symptoms in Parkinson's disease (PD) patients with that of control subjects (CS) suffering from non-neurological medical illnesses. METHODS: One-hundred PD patients and 100 CS were submitted to a structured clinical interview for identification of major depressive disorder (MDD) and minor depressive disorder (MIND), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), criteria. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) were also administered to measure depression severity. RESULTS: When considering the whole groups, there were no differences in depressive symptom frequency between PD and CS apart from worthlessness/guilt, and changes in appetite reduced rates in PD. Further, total scores and psychic and somatic subscores of HDRS and BDI did not differ between PD and CS. After we separated PD and CS in those with MDD, MIND, and no depression (NODEP), comparing total scores and psychic/somatic subscores of HDRS and BDI, we found increased total depression severity in NODEP PD and reduced severity of the psychic symptoms of depression in MDD PD, with no differences in MIND. However, the severity of individual symptom frequency of depression was not different between PD and CS in MDD, MIND, and NODEP groups. CONCLUSION: Although MDD and MIND phenomenology in PD may be very similar to that of CS with non-neurological medical illnesses, neurological symptoms of PD may worsen (or confound) depression severity in patients with no formal/structured DSM-IV-TR, diagnosis of depressive mood disorders. Thus, a thorough assessment of depression in PD should take into consideration the different impacts of neurological manifestations on MDD, MIND, and NODEP.

L-Acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine.

INTRODUCTION: L-Acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with dysthymic disorder in comparison with a traditional antidepressant such as fluoxetine. METHODS: Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of dysthymic disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments. RESULTS: Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression. DISCUSSION: The results obtained with LAC and fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity.

The natural history of multiple system atrophy: a prospective European cohort study.

BACKGROUND: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. METHODS: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. FINDINGS: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1-11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09-3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02-4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5-0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1-10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. INTERPRETATION: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials.

Hedonic tone and its mood and cognitive correlates in Parkinson's disease.

BACKGROUND: Anhedonia has been mainly reported as a symptom of depression and cognitive impairment in Parkinson's disease (PD) patients. Here, we investigated whether hedonic tone depends on depression and clarified its relationship with the cognitive performance of PD patients with different mood disorders. METHODS: In 254 patients, we assessed hedonic tone using the Snaith-Hamilton Pleasure Scale, depression severity using the Beck Depression Inventory, and cognitive performances using the Mental Deterioration Battery. A structural psychiatric interview was used to diagnose major depressive disorder (MDD) and minor depressive disorder (MIND), according to the DSM-IV-TR criteria. RESULTS: PD patients with diagnosis of MDD were more anhedonic than those with MIND and those without depressive disorders. Reduced hedonic tone correlated with depression severity in patients with MDD and no depressive disorders. In multivariate models that consider depression severity and cognitive performances together, anhedonia was related to increased depression severity and episodic memory (auditory-verbal learning) impairment, in patients with MDD and with increased depression severity and attention impairment in patients with no depressive disorders. In patients with MIND, anhedonia did not correlate with depression severity or any cognitive performance score. DISCUSSION: Our findings suggest that anhedonia is related to depression severity and specific cognitive performances in patients with MDD and with no depressive disorder. By contrast, the reduced hedonic tone in patients with MIND is independent from depression severity and cognition. Thus, anhedonia in PD is a heterogeneous and multidimensional phenomenon and require investigation at different levels.

A non-comparative assessment of tolerability and efficacy of duloxetine in the treatment of depressed patients with Parkinson's disease.

OBJECTIVE: Depression is a comorbidity affecting quality of life (QoL) in patients with Parkinson's disease (PD) and requires appropriate treatment. This study evaluated the tolerability, safety, and efficacy of duloxetine 60 mg once daily for 12 weeks in PD patients with major depressive disorder (MDD). RESEARCH AND DESIGN METHODS: Non-comparative, open-label, multi-center study. MAIN OUTCOME MEASURES: Tolerability was evaluated by discontinuation rate (acceptable if ≤ 19%) due to treatment-emergent adverse events (TEAEs) and motor symptoms (UPDRS). Safety measures were TEAEs, the UKU side effect rating scale, vital signs, weight, laboratory tests, and ECG. Efficacy measures included HAMD-17, BDI, CGI-S, PGI-I, and pain VAS. QoL was measured by PDQ-39. RESULTS: Of the 151 patients enrolled, 8.6% (95% upper CI: 13.3%) discontinued the study due to TEAEs. Worsening in PD-related tremor and rigidity was not observed, activities of daily living significantly improved and UKU subscales progressively decreased. Clinically significant abnormalities in laboratory findings were limited to four cases of hypercholesterolemia and one increase of total bilirubin, CPK, and fasting glucose. Blood pressure, weight, and ECG did not change from baseline. HAMD-17 and PDQ-39 total score and individual domains, BDI, CGI-S, and PGI-I total scores significantly improved. CONCLUSIONS: Duloxetine seems well tolerated and likely effective in the treatment of depression associated with PD, with no detrimental effects in PD signs and symptoms.

The progression of non-motor symptoms in Parkinson's disease and their contribution to motor disability and quality of life.

Non-motor symptoms are gaining relevance in Parkinson's disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1-10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (H&Y) stage was used to categorize patient status (I-II mild; III moderate; IV-V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening (p < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months (p < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones (p < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.

Sad and happy facial emotion recognition impairment in progressive supranuclear palsy in comparison with Parkinson's disease.

The severity of motor and non-motor symptoms of progressive supranuclear palsy (PSP) has a profound impact on social interactions of affected individuals and may, consequently, contribute to alter emotion recognition. Here we investigated facial emotion recognition impairment in PSP with respect to Parkinson's disease (PD), with the primary aim of outlining the differences between the two disorders. Moreover, we applied an intensity-dependent paradigm to examine the different threshold of encoding emotional faces in PSP and PD. The Penn emotion recognition test (PERT) was used to assess facial emotion recognition ability in PSP and PD patients. The 2 groups were matched for age, disease duration, global cognition, depression, anxiety, and daily L-Dopa intake. PSP patients displayed significantly lower recognition of sad and happy emotional faces with respect to PD ones. This applied to global recognition, as well as to low-intensity and high-intensity facial emotion recognition. These results indicate specific impairment of recognition of sad and happy facial emotions in PSP with respect to PD patients. The differences may depend upon diverse involvement of cortical-subcortical loops integrating emotional states and cognition between the two conditions, and might represent a neuropsychological correlate of the apathetic syndrome frequently encountered in PSP.

The validity and reliability of the Italian Olfactory Identification Test (IOIT) in healthy subjects and in Parkinson's disease patients.

BACKGROUND: Olfactory function can be rapidly evaluated by means of standardized olfactory tests. Multiple-choice smell identification tests can be conditioned by cultural background. To investigate a new tool for detecting olfactory deficit in Italian subjects we developed a multiple-choice identification test prepared with odorants belonging to the Italian culture. METHODS: The Italian Olfactory Identification Test (IOIT) was developed with 33 microencapsulated odorants with intensity of odors and headspace Gas Chromatography being tested. Test-retest reliability of the IOIT was evaluated. The IOIT was administered to 511 controls and 133 Parkinson's patients. RESULTS: In healthy subjects the number of IOIT errors increased with age for both females (p < 0.0001) and males (p < 0.0001), while in the Parkinson's disease group the number of IOIT errors was significantly greater where compared to healthy subjects (p < 0.0001 in all age groups). The reference limits applied to all age groups revealed an IOIT sensitivity of 93% and a specificity of 99%. The test-retest reliability was excellent. CONCLUSION: The IOIT is highly reliable, disposable, easy to administer, not fragile, and has a long shelf-life. All these features make the IOIT suitable for clinical use as well as for population screening and to discriminate Parkinson's patients from healthy subjects.

Psychosis associated to Parkinson's disease in the early stages: relevance of cognitive decline and depression.

OBJECTIVE: To evaluate the prevalence of psychosis associated with Parkinson's disease (PSY-PD) in its early stages, its incidence over a 24 month follow-up period and the association with motor and non-motor clinical features. METHODS: PRIAMO is a 2 year longitudinal observational study that has enrolled patients with parkinsonism in 55 Italian centres. A cohort of 495 patients with early disease stage PD (baseline Hoehn and Yahr score ≤ 2, disease's duration (median) 3.4 years) were followed for 2 years. PSY-PD was evaluated by means of a clinician rated questionnaire and defined as the presence of at least one of the following symptoms occurring for at least 1 month: illusions, hallucinations, jealousy ideas and persecutory ideas. Patients with and without PSY-PD were compared on several clinical variables, encompassing motor and non-motor features. RESULTS: The prevalence of PSY-PD at baseline was 3%; the incidences at 12 and 24 months were 5.2% and 7.7%, respectively. Longer disease duration and prescription of dopamine agonists at baseline were associated with the development of PSY-PD over the 24 month period. At this follow-up time, worse disease severity, decline in cognitive performances, presence of depressive symptoms and anxiety were more frequently observed in PSY-PD. CONCLUSIONS: Psychotic type symptoms may occur in the early stages of PD although less frequently than in later stages. Beyond dopaminergic treatment, there are disease related factors, such as disease severity and the occurrence of cognitive and depressive symptoms, which may underlie the onset of psychotic type symptoms from the earliest stages.