Italian Parkinson's Disease Research Articles

Assessment of the psychometric properties of the Italian version of the New Freezing of Gait Questionnaire (NFOG-Q-IT) in people with Parkinson disease: a validity and reliability study.

Freezing of gait (FOG) in Parkinson's disease (PD) is a challenging clinical symptom to assess, due to its episodic nature. A valid and reliable tool is the New FOG Questionnaire (NFOG-Q) used worldwide to measure FOG symptoms in PD. The aim of this study was to translate, to culturally adapt, and to test the psychometric characteristics of the Italian version of the NFOG-Q (NFOG-Q-It). The translation and cultural adaptation was based on ISPOR TCA guidelines to finalize the 9-item NFOG-Q-It. Internal consistency was assessed in 181 Italian PD native speakers who experienced FOG using Cronbach's alpha. Cross-cultural analysis was tested using the Spearman's correlation between the NFOG-Q-It and the Modified Hoehn-Yahr Scale (M-H&Y). To assess construct validity, correlations among NFOG-Q-It, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Falls Efficacy Scale-International (FES-I), the 6-min Walking Test (6MWT), the Mini Balance Evaluation System Test (Mini-BESTest) and the Short Physical Performance Battery (SPPB) were investigated. The Italian N-FOGQ had high internal consistency (Cronbach's α = 0.859). Validity analysis showed significant correlations between NFOG-Q-IT total score and M-H&Y scores (r = 0.281 p < 0.001), MDS-UPDRS (r = 0.359 p < 0.001), FES-I (r = 0.230 p = 0.002), Mini BESTest (r = -0.256 p = 0.001) and 6MWT (r = -0.166 p = 0.026). No significant correlations were found with SPPB, MOCA and MMSE. The NFOG-It is a valuable and reliable tool for assessing FOG symptoms, duration and frequency in PD subjects. Results provide the validity of NFOG-Q-It by reproducing and enlarging previous psychometric data.

Analysis of Genetic and Non-genetic Predictors of Levodopa Induced Dyskinesia in Parkinson's Disease.

Background: Levodopa (L-Dopa), representing the therapeutic gold standard for the treatment of Parkinson disease (PD), is associated with side effects like L-Dopa induced dyskinesia (LID). Although several non-genetic and genetic factors have been investigated for association with LID risk, contrasting results were reported and its genetic basis remain largely unexplored. Methods: In an Italian PD cohort (N = 460), we first performed stepwise multivariable Cox Proportional Hazard regressions modeling LID risk as a function of gender, PD familiarity, clinical subtype, weight, age-at-onset (AAO) and years-of-disease (YOD), L-Dopa dosage, severity scores, and scales assessing motor (UPDRS-III), cognitive (MoCA), and non-motor symptoms (NMS). Then we enriched the resulting model testing two variants—rs356219 and D4S3481—increasing the expression of the SNCA gene, previously suggested as a potential mechanism of LID onset. To account for more complex (non-linear) relations of these variables with LID risk, we built a survival random forest (SRF) algorithm including all the covariates mentioned above. Results: Among tested variables (N = 460 case-complete, 211 LID events; total follow-up 31,361 person-months, median 61 months), disease duration showed significant association (p < 0.005), with 6 (3–8)% decrease of LID risk per additional YOD. Other nominally significant associations were observed for gender—with women showing a 39 (5–82)% higher risk of LID—and AAO, with 2 (0.3–3)% decrease of risk for each year increase of PD onset. The SRF algorithm confirmed YOD as the most prominent feature influencing LID risk, with a variable importance of about 8% in the model. In genetic models, no statistically significant effects on incident LID risk was observed. Conclusions: This evidence supports a protective effect of late PD onset and gender (men) against LID risk and suggests a new independent protective factor, YOD. Moreover, it underlines the importance of personalized therapeutic protocols for PD patients in the future.

Self-reported needs of patients with Parkinson's disease during COVID-19 emergency in Italy.

Because of COVID-19 outbreak, regular clinical services for Parkinson’s disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9–21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients’ needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.

SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients.

Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.

Quality of life in Parkinson's disease: Italian validation of the Parkinson's Disease Questionnaire (PDQ-39-IT).

Translation and cross-cultural adaptation of the 39-item Parkinson's Disease Questionnaire (PDQ-39) to the Italian culture was performed by Oxford University Innovation in 2008, but this version has never been validated. Therefore, we performed the process of validation of the Italian version of the PDQ-39 (PDQ-39-IT) following the "Consensus-Based Standards for the Selection of Health Status Measurement Instruments" checklist. The translated PDQ-39-IT was tested with 104 patients diagnosed with Parkinson's disease (PD) who were recruited between June and October 2017. The mean age of the participants was 65.7 ± 10.2years, and the mean duration of symptoms was 7.4 ± 5.3years. The internal consistency of the PDQ-39-IT was assessed by Cronbach's alpha and ranged from 0.69 to 0.92. In an assessment of test-retest reliability in 35 of the 104 patients, the infraclass correlation coefficient (ICC) ranged from 0.85 to 0.96 for the various subitems of the PDQ-39-IT (all p < 0.01). Spearman's rank correlation coefficient for the validity of the PDQ-39-IT and the Italian version of the 36-Item Short Form (SF-36) was - 0.50 (p < 0.01). The results show that the PDQ-39-IT is a reliable and valid tool to assess the impact of PD on functioning and well-being. Thus, the PDQ-39-IT can be used in clinical and research practice to assess this construct and to evaluate the overall effect of different treatments in Italian PD patients.

Factors influencing psychological well-being in patients with Parkinson's disease.

BackgroundBoth motor and non-motor symptoms could contribute to significant deterioration of psychological well-being in patients with Parkinson's disease (PD). However, its assessment has been only indirectly evaluated using tools based on health-related quality of life (HRQoL), such as the PDQ-39 scale.ObjectivesTo evaluate psychological well-being in PD using a specific tool of assessment, the Psychological Well-being Scale (PWS), and its clinical correlates.MethodsThis article reports data of patients’ perception of health state, as measured by means of the PWS, from an epidemiological, cross-sectional study conducted in Italian PD patients (FORTE Study). We tested possible relationship between well-being and clinical characteristics including fatigue, depression, sleep disruption and HRQoL.Results272 patients completed the PWS questionnaire. Significant and clinically-relevant correlations were found between PWS total score and Parkinson’s Fatigue Scale, Beck Depression Inventory, UPDRS Section I, PD Sleep Scale and PDQ-39 for HRQoL scores. Only clinically negligible correlations were found between PWS and motor scores.ConclusionsNon-motor symptoms have a significant impact on psychological well-being in PD patients.

Dietary habits in Parkinson's disease: Adherence to Mediterranean diet

IntroductionOur objective is to describe the dietary habits, food preferences and adherence to Mediterranean diet (MeDi) of a large sample of Italian Parkinson's Disease (PD) patients compared to a group of controls. MethodsDietary habits of 600 PD patients from throughout Italy and 600 controls matched by gender, age, education, physical activity level and geographical residence, were collected using the ON-GP Food Frequency Questionnaire. Then, we compared patients by disease duration and the presence of swallowing disturbances. ResultsOverall, adherence of PD patients (males, 53.8%; mean disease duration, 9.2 ± 7.0 years) to MeDi was similar to controls (score, 4.8 ± 1.7 vs. 4.9 ± 1.6; P = 0.294). Patients consumed less alcohol and fish and drank significantly less water, coffee, and milk which resulted also in lower total fluids intake. On the contrary, they ate more fruit, cooked vegetables, cereals and baked items, more dressings and more sweets in general. Disease duration was associated with increased intake of several food groups but it was not associated with changes in MeDi score (P = 0.721). Patients with swallowing disturbances (n = 72) preferred softer and more viscous food but preferences did not result in differences in dietary pattern. However, patients with dysphagia drank less fluids (P = 0.043). DiscussionPD patients presented different dietary habits and food preferences compared to the general population and adherence to MeDi was not associated with disease duration. Self-reported dysphagia was associated with reduced intake of fluids. These aspects may be amenable to change in order to improve the management of nutritional issues in this patient population.

Adaptation and psychometric properties of the Italian version of the Non-Motor Symptoms Questionnaire for Parkinson's disease.

Although non-motor symptoms (NMS) of Parkinson's disease (PD) are very common also in early stages of the disease, they are still under-recognized. Screening tools for non-motor symptoms, such as non-motor symptoms questionnaire (NMSQuest), help clinicians to recognize NMS and to evaluate if patients could require further assessment or specific treatments. To validate an adapted Italian version of NMSQuest and study its psychometric properties, Italian PD patients self-completed Italian NMSQuest, and then underwent a standard clinical evaluation including motor assessment (by Hoehn and Yahr staging, unified Parkinson's disease rating scale part III) and non-motor assessment (by Montreal cognitive assessment, Beck depression inventory, neuropsychiatric inventory, Epworth sleepinessscale, scale for outcomes in Parkinson's disease-Autonomic and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale part I). Somatic comorbidities were quantified using the modified cumulative illness rating scale (CIRS). Seventy-one subjects were assessed (mean age years 69.8±9.6 SD; 31% women; mean duration of disease 6.3±4.6years; H&Y median 2). Italian NMSQuest showed adequate satisfactory clinimetrics in terms of data quality, precision, acceptability, internal consistency and reliability. A significant correlation was found between NMSQuest and most of non-motor assessment scales, while no significant correlation appeared with motor severity as well as with age of patients, disease duration, levodopa equivalent daily dose, L-DOPA/dopamine agonists assumption and CIRS total score. The Italian version of the NMSQuest resulted as a reliable instrument for screening NMS in Italian PD patients.

Polymorphisms of dopamine receptor genes are associated to increased risk of visual hallucinations in Italian Parkinson's disease patients

Polymorphisms of dopamine receptor genes are associated to increased risk of visual hallucinations in Italian Parkinson's disease patients

Parkinson's Disease Sleep Scale 2: application in an Italian population.

Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients.

Anxiety and depression in Parkinson's disease patients in Saudi Arabia Global neurology

Parkinson's disease is the most common movement disorder in Saudi Arabia. Among the most common non-motor symptoms of PD are anxiety and depression. Mental health disorders, however, still remain taboo subjects in the region. This brief article sheds light on a small study conducted on Saudi PD patients, and discusses current challenges for managing them in the region. Given the wider readership of JNS's Global Neurology, this piece is hoped to appeal to the appropriate audience. Classically a motor disorder, Parkinson's disease (PD) results in many non-motor symptoms, some of which have been recognised since the first description of the “shaking palsy” by James Parkinson [1]. Only recently, however, research on non-motor symptoms of PD has gainedmomentum [2–4]. The PRIAMO study evaluated 1072 Italian PD patients and observed that 98.6% of PD patients experienced such symptoms [5]. Psychological complaints were the most common, including anxiety in 56% and depression in 22.5% patients [5]. Sociocultural factors have been shown to influence the prevalence [6,7], perception [8] and even clinical presentation of anxiety and depression [9,10]. Large-scale epidemiological studies on mental health disorders are largely lacking in Saudi Arabia, as most studies involve selective patient samples (e.g. medical students or dialysis patients) [11–13]. In a cross-sectional study from South-eastern Saudi Arabia on general practice patients (n = 280), around 10% screened positively for depression [14]. Little is known about the prevalence and nature of anxiety and depression in PD patients in Saudi Arabia. In a clinical study [15] that alluded to non-motor symptoms in 54 PD patients in Saudi Arabia, depression was the second most prevalent symptom, exceeded only by constipation. The only available data on anxiety and depression come from a small cohort (n=18) of Saudi PD patients (Alamri, unpublished).When compared with another ageand sex-matched cohort from New Zealand (n = 30), Saudi PD patients scored significantly higher on the HADS depression subscale (mean 11.7 vs. 9.5, p = 0.004), but not anxiety subscale (4.7 vs. 5.6, p = 0.36) or the total HADS scores (11.7 vs. 9.5, p = 0.23).

Clinical variables associated with treatment changes in Parkinson’s disease: results from the longitudinal phase of the REASON study

To assess over a period of 9 months in a sample of Italian Parkinson's disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients' causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3 months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist's and patient's perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 % of the patients, while only 36 % of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap.

Association of nicotine dependence susceptibility gene, CHRNA5, with Parkinson's disease age at onset: Gene and smoking status interaction

BackgroundSmoking is a well documented environmental factor that reduces susceptibility to Parkinson's disease (PD). Several genetic variants within the nicotinic cholinergic receptor gene cluster, CHRNA5-CHRNA3-CHRNB4 have been reported to be associated with nicotine dependence (ND), and this association has been validated in multiple studies. ObjectivesDue to the inverse correlation between smoking and PD susceptibility, we investigated whether ND-related genetic variants are associated with age at onset (AAO) of PD among smokers. MethodsWe performed a genetic association study in a sample of 677 Italian PD patients, ages 34–76. 438 had never smoked (NS), and 239 were current or past smokers (ever-smokers, ES). Three independent SNPs within the CHRNA5-CHRNA3-CHRNB4 gene cluster (rs588765, rs16969968, rs578776) were analyzed for association with AAO. ResultsWe demonstrated an interaction between the rs588765 SNP and smoking status (NS vs. ES) that was nominally significant in its effect on PD AAO (p = 0.04). The rs588765 ND risk allele ‘C’ was associated with delayed AAO among ES (even when smoking intensity variables are accounted for), but had no significant effect among NS. In the ES group, a dominant model of inheritance was observed: carriers of the ‘CC’ genotype presented delayed AAO compared to carriers of the ‘CT’ or ‘TT’ genotypes. ConclusionOur preliminary results suggest that the ND risk variant, rs588765, has a protective effect in PD, and is associated with later AAO, but only when the individual was previously exposed to nicotine. This may be explained by modulating the neuroprotective effect of chronic nicotine exposure against striatal dopaminergic damage. Further validation studies in additional populations are required.

Observational study of sleep-related disorders in Italian patients with Parkinson’s disease: usefulness of the Italian version of Parkinson’s disease sleep scale

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.

Mutant Parkin Impairs Mitochondrial Function and Morphology in Human Fibroblasts

BackgroundMutations in Parkin are the most common cause of autosomal recessive Parkinson disease (PD). The mitochondrially localized E3 ubiquitin-protein ligase Parkin has been reported to be involved in respiratory chain function and mitochondrial dynamics. More recent publications also described a link between Parkin and mitophagy.Methodology/Principal FindingsIn this study, we investigated the impact of Parkin mutations on mitochondrial function and morphology in a human cellular model. Fibroblasts were obtained from three members of an Italian PD family with two mutations in Parkin (homozygous c.1072delT, homozygous delEx7, compound-heterozygous c.1072delT/delEx7), as well as from two relatives without mutations. Furthermore, three unrelated compound-heterozygous patients (delEx3-4/duplEx7-12, delEx4/c.924C>T and delEx1/c.924C>T) and three unrelated age-matched controls were included. Fibroblasts were cultured under basal or paraquat-induced oxidative stress conditions. ATP synthesis rates and cellular levels were detected luminometrically. Activities of complexes I-IV and citrate synthase were measured spectrophotometrically in mitochondrial preparations or cell lysates. The mitochondrial membrane potential was measured with 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide. Oxidative stress levels were investigated with the OxyBlot technique. The mitochondrial network was investigated immunocytochemically and the degree of branching was determined with image processing methods. We observed a decrease in the production and overall concentration of ATP coinciding with increased mitochondrial mass in Parkin-mutant fibroblasts. After an oxidative insult, the membrane potential decreased in patient cells but not in controls. We further determined higher levels of oxidized proteins in the mutants both under basal and stress conditions. The degree of mitochondrial network branching was comparable in mutants and controls under basal conditions and decreased to a similar extent under paraquat-induced stress.ConclusionsOur results indicate that Parkin mutations cause abnormal mitochondrial function and morphology in non-neuronal human cells.

Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene

The Grb10-Interacting GYF Protein-2 (GIGYF2) gene has been proposed as the Parkinson-disease (PD) gene underlying the PARK11 locus. However, association of GIGYF2 with PD has been challenged and a functional validation of GIGYF2 mutations is lacking. In this frame, we performed a mutational screening of GIGYF2 in an Italian PD cohort. Exons containing known mutations were analyzed in 552 cases and 552 controls. Thereafter, a subset of 184 familial PD cases and controls were subjected to a full coding-exon screening. These analyses identified 8 missense variations in 9 individuals (4 cases, 5 controls). Furthermore, we developed a zebrafish model of gigyf2 deficiency. Abrogation of gigyf2 function in zebrafish embryos did not lead to a drastic cell loss in diencephalic dopaminergic (DA) neuron clusters, suggesting that gigyf2 is not required for DA neuron differentiation. Notably, gigyf2 functional abrogation did not increase diencephalic DA neurons susceptibility to the PD-inducing drug MPP+. These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene.

Genetic polymorphism of Angiotensin-Converting Enzyme is not associated with the development of Parkinson's disease and of l-dopa-induced adverse effects

Sporadic Parkinson's disease (PD) is a frequent neurodegenerative movement disorder. Both environmental and genetic factors have been studied in the etiology of PD. Among genetic factors, increasing evidences suggest that deletion/insertion (D/I) gene polymorphism of the angiotensin I-converting enzyme (ACE) may be involved in the pathogenesis of PD and in the occurrence of the adverse effects of chronic l-dopa therapy. We investigated this hypothesis by evaluating the frequency of the ACE gene D/I polymorphism in 120 Italian PD patients and 132 controls. Out of the 120 PD patients, 91 were under chronic l-dopa treatment. Our results revealed no difference in ACE I/D genotype ( χ 2 = 0.79, p = 0.66) and allele ( χ 2 = 0.34, p = 0.56) frequencies between PD and controls. We also failed to observe any significant association with the occurrence of l-dopa-induced adverse effects in long-term treated PD patients, thereby excluding the presence of an association between ACE I/D genotypes and the genetic susceptibility to PD and the development of adverse effect of chronic l-dopa therapy.

HFE gene mutations in a population of Italian Parkinson's disease patients

An abnormal accumulation and distribution of brain iron are common to different neurodegenerative disorders, including Parkinson's disease (PD), and alteration of genes involved in iron metabolism cause neurodegeneration with brain iron accumulation. HFE participates in the regulation of iron metabolism, its mutations are primary cause of hereditary hemochromatosis and appear to be more frequent in neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis. However, conflicting results were obtained in previous studies aimed to verify if nucleotide variations in HFE gene act as risk modifiers for PD. We used denaturing HPLC for scanning DNA sequence variations in exon 2 and 4 of HFE gene in a cohort of 475 Italian PD patients. We identified the most common H63D, C282Y and S65C, and also other 4 rare mutation types (R66H, R224W, E277K, and T281M). The allele frequency of H63D and C282Y was not statistically different from that of 2 control groups with similar mean age or of a large cohort of the same geographical area. In addition we could not find statistical differences in the clinical phenotypes of patients carrying at least one mutated HFE allele from those with the normal allele. We conclude that in the Italian population, the most common HFE mutations, H63D and C282Y are not associated with the individual risk to develop PD, nor have specific influence on the clinical features of the disease.

Parkin polymorphisms and environmental exposure: Decrease in age at onset of Parkinson's disease

We tested the hypothesis that parkin polymorphisms (SNPs) and environmental exposure (EE) interact to reduce the age of onset of idiopathic Parkinson disease (PD). We prospectively and consecutively enrolled a total of 81 Italian PD patients. The diagnosis of PD was based on the UK Parkinson's Disease Society's brain bank criteria. Twenty-one patients with a positive family history for PD or tremor were excluded from the study. We collected information about medical history and EE. PARK1, PARK2 genes and PARK8 (exon 41) were screened. We detected one parkin mutation in a single patient and three parkin polymorphisms in a total of 25 patients; no alpha synuclein mutations, no common mutations of LRKK2 gene were found. The mutation-positive patient has been excluded from the study. The cohort of the remaining 59 patients has been divided into four subgroups, according to the presence/absence of parkin polymorphisms and the presence/absence of environmental factors-exposure. The age of onset of PD was significantly lower in patients with both SNPs and EE as compared to patients without (62.18 ± 9.5 years versus 71.62 ± 8 years, p = 0.024; −13%). Patients with either SNPs or EE had an intermediate age of onset. The association of parkin polymorphisms and environmental exposure has a strong effect in lowering the age of onset of PD; the effect of environmental exposure or parkin polymorphisms alone seems to influence modestly the age of onset of PD. Individuals with environmental/occupational exposure should be screened for the presence of parkin SNPs.

Frequency of the LRRK2 G2019S mutation in Italian patients affected by Parkinson's disease

Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) have been identified in both dominant and sporadic cases affected by Parkinson's disease (PD). The LRRK2 G2019S mutation (c.6055G>A) is the most frequent substitution in Caucasians, accounting for approximately 5-6% of familial and 0.5-2.0% of apparently sporadic PD cases. We investigated the frequency of the LRRK2 G2019S mutation in 98 unrelated Italian PD patients, including 12 probands belonging to families compatible with autosomal dominant inheritance (12%) and 86 sporadic cases (88%). We detected the G2019S mutation in one sporadic female patient (1.2%). These results confirm that the G2019S mutation is a relevant cause of sporadic PD cases in the Italian population and stress the importance of performing this genetic test, which has important implications for genetic counselling.