Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Brain plasticity and hearing disorders.

Permanently changed sensory stimulation can modify functional connectivity patterns in the healthy brain and in pathology. In the pathology case, these adaptive modifications of the brain are referred to as compensation, and the subsequent configurations of functional connectivity are called compensatory plasticity. The variability and extent of auditory deficits due to the impairments in the hearing system determine the related brain reorganization and rehabilitation. In this review, we consider cross-modal and intra-modal brain plasticity related to bilateral and unilateral hearing loss and their restoration using cochlear implantation. Cross-modal brain plasticity may have both beneficial and detrimental effects on hearing disorders. It has a beneficial effect when it serves to improve a patient's adaptation to the visuo-auditory environment. However, the occupation of the auditory cortex by visual functions may be a negative factor for the restoration of hearing with cochlear implants. In what concerns intra-modal plasticity, the loss of interhemispheric asymmetry in asymmetric hearing loss is deleterious for the auditory spatial localization. Research on brain plasticity in hearing disorders can advance our understanding of brain plasticity and improve the rehabilitation of the patients using prognostic, evidence-based approaches from cognitive neuroscience combined with post-rehabilitation objective biomarkers of this plasticity utilizing neuroimaging.

The PRIAMO study: active sexual life is associated with better motor and non-motor outcomes in men with early Parkinson's disease.

BACKGROUND AND PURPOSE: Data suggest a relationship between sexual dysfunction, mainly erectile dysfunction in men, and worse disease progression in Parkinson's disease (PD). There is scant evidence on the correlates of sexual activity in PD patients. By involving a subgroup of 355 patients from the PRIAMO (Parkinson Disease Non Motor Symptoms) study, the present 24-month longitudinal prospective analysis aims to demonstrate that the presence of active sexual life is associated with disease progression in early PD. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models showed that gastrointestinal symptoms [odds ratio 0.56, 95% confidence interval (CI) 0.39-0.82, P = 0.003] and apathy (odds ratio 0.42, 95% CI 0.29-0.63, P < 0.001) were less likely to be associated with sexual activity in men. Analysis also demonstrated that sexual activity in men was associated with lower motor disability (coefficient -2.881, 95% CI -4.732 to -1.030, P = 0.002), better quality of life (coefficient -24.196, 95% CI -44.884 to -3.508, P = 0.022; coefficient 0.083, 95% CI 0.023-0.143, P = 0.006) and lower depression scores (coefficient -1.245, 95% CI -2.104 to -0.387, P = 0.004). No association was shown in women. CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients suggesting that sexual activity is associated with lower motor and non-motor disability as well as with better quality of life in men. These findings should prompt movement disorders specialists to periodically inquiry about their patients' sexual life.

Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.

BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years. METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years. RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up. CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.

Diffuse alveolar haemorrage as initial presentation of systemic lupus erythematosus: a case report.

Diffuse alveolar haemorrhage (DAH) is a rare life-threatening complication of systemic lupus erythematosus (SLE), associated with high mortality rates. It usually occurs in patients with an established diagnosis of SLE. It has been reported as the initial presentation of SLE in 11-20% of cases. It occurs most frequently in females. We describe the case of a child, aged 14 years, with fever, asthenia, haemoptysis, dyspnea, anaemia, increased inflammatory markers, positivity to ANA, nDNA, direct Coombs tests, anticardiolipin antibodies and complement factors consumption. Computed tomography (CTscan) of the chest showed bilateral pulmonary alveolar infiltrates. He also developed renal involvement with nephritis later in the course of the disease. He was started on the treatment approved by the Euro Lupus Protocol for critical patients. After starting Mycophenolate Mofetil the clinical and radiological features were improved as was the survival outcome.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

The PRIAMO study: urinary dysfunction as a marker of disease progression in early Parkinson's disease.

BACKGROUND AND PURPOSE: New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life (coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95% CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability (coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.

The non-motor side of the honeymoon period of Parkinson's disease and its relationship with quality of life: a 4-year longitudinal study.

BACKGROUND AND PURPOSE: Very little is known about the progression of non-motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of de-novo, previously untreated, patients with PD. METHODS: Consecutive de-novo (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non-motor features as well as of quality of life measures. RESULTS: Sixty-one patients were prospectively followed-up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa-equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life. CONCLUSIONS: Non-motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non-dopaminergic networks and consider NMSs in their outcomes.

Increased audiovisual integration in cochlear-implanted deaf patients: independent components analysis of longitudinal positron emission tomography data.

It has been demonstrated in earlier studies that patients with a cochlear implant have increased abilities for audio-visual integration because the crude information transmitted by the cochlear implant requires the persistent use of the complementary speech information from the visual channel. The brain network for these abilities needs to be clarified. We used an independent components analysis (ICA) of the activation (H2(15)O) positron emission tomography data to explore occipito-temporal brain activity in post-lingually deaf patients with unilaterally implanted cochlear implants at several months post-implantation (T1), shortly after implantation (T0) and in normal hearing controls. In between-group analysis, patients at T1 had greater blood flow in the left middle temporal cortex as compared with T0 and normal hearing controls. In within-group analysis, patients at T0 had a task-related ICA component in the visual cortex, and patients at T1 had one task-related ICA component in the left middle temporal cortex and the other in the visual cortex. The time courses of temporal and visual activities during the positron emission tomography examination at T1 were highly correlated, meaning that synchronized integrative activity occurred. The greater involvement of the visual cortex and its close coupling with the temporal cortex at T1 confirm the importance of audio-visual integration in more experienced cochlear implant subjects at the cortical level.

Presence and progression of non-motor symptoms in relation to uric acid in de novo Parkinson's disease.

BACKGROUND AND PURPOSE: Uric acid (UA) has been studied extensively as a valuable biomarker of Parkinson's disease (PD), but its relationship with non-motor symptoms (NMS) in de novo PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD. METHODS: Sixty-nine newly diagnosed PD patients were enrolled. At baseline, all patients completed the NMS questionnaire (NMSQuest), and serum UA levels were measured. After 2 years, the NMSQuest was completed again and patients were categorized into four groups: NMS improvement (domain involvement at baseline but not at 2-year follow-up visit), NMS absence (domain not involved at baseline or 2-year follow-up visits), NMS presence (domain involvement both at baseline and 2-year follow-up visits) and NMS worsening (domain not involved at baseline but involved at 2-year follow-up). RESULTS: ANOVA with post hoc Bonferroni correction showed that patients with NMS absence presented significantly higher UA values than patients with NMS presence with regard to the attention/memory (P = 0.023), depression/anxiety (P = 0.028) and cardiovascular domains (P = 0.002), whilst no differences were found with regard to both the NMS improvement and worsening groups. In addition, multinomial regression analysis showed that the lowest tertile of NMS progression presented higher UA levels (P = 0.023; odds ratio 0.488) compared with patients with greater NMS progression. CONCLUSIONS: This is the first report of a relationship between serum UA and presence/progression of multiple NMS in de novo PD, providing additional evidence of the reliability of UA as a biomarker of PD and opening new insights on PD neuroprotection.

A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson's disease patients.

BACKGROUND AND PURPOSE: Depressed mood is a common psychiatric problem associated with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline treatment. METHODS: ACCORDO (see the ) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson's disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. RESULTS: One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline -5.46 ± 0.73 vs. placebo -3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). CONCLUSIONS: Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes.

Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.

BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy. METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests. RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up. CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.

Increased bilirubin levels in de novo Parkinson's disease.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Uric acid relates to dopamine transporter availability in Parkinson's disease.

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 STUDY: We 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. RESULTS: Pearson'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.

Cognitive performances and DAT imaging in early Parkinson's disease with mild cognitive impairment: a preliminary study.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Although preliminary, our results suggest that striatal dopamine depletion may contribute to some cognitive deficit in early never treated PD patients with MCI.

A weighted and directed interareal connectivity matrix for macaque cerebral cortex.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks.

Subthreshold depression and subjective cognitive complaints in Parkinson's disease.

BACKGROUND AND PURPOSE: Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients. METHODS: Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions. RESULTS: On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients. CONCLUSIONS: SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being.

Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). METHODS: In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.). RESULTS: Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. CONCLUSIONS: These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

Insulin-like growth factor-1 predicts cognitive functions at 2-year follow-up in early, drug-naïve Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. METHODS: Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2 years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. RESULTS: At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. CONCLUSIONS: Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up.