Michela Zini

Istituti Clinici di Perfezionamento, Milano, Lombardy, Italy

Are you Michela Zini?

Claim your profile

Publications (24)119.5 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study investigated cognitive functions in Parkinson's disease (PD) patients with impulse control disorders (ICDs) and aimed to identify possible predictors of behavioral outcome. In this longitudinal cohort study, 40 PD outpatients with ICDs and 40 without, were matched for sex, age at PD onset, age and disease duration at cognitive assessment. All patients had two neuropsychological assessments at least 2 years apart (mean, 3.5 years). Multivariate logistic regression analysis was performed to identify predictors of ICDs remission at follow-up. The PD patients with and without ICDs had overall comparable cognitive performance at baseline. When evaluating changes between baseline and follow-up, we found significant group × time interactions in several frontal lobe-related tests, with the ICDs group showing a less pronounced worsening over time. ICDs remission was associated with better performance at baseline in working memory-related tasks, such as digit span (odds ratio [OR] = 2.69 [95% confidence interval (CI), 1.09-6.66]) and attentive matrices (OR=1.19 [95%CI, 1.03-1.37]). ICDs remitters and non-remitters had no remarkable differences in baseline PD-related features and therapy management strategies (including the extent of dopamine agonist dose reduction). In conclusion, ICDs in PD patients are not related to greater cognitive impairment or executive dysfunction, but rather show relatively lower cognitive decline over time. The impaired top-down inhibitory control characterizing ICDs is likely attributable to a drug-induced overstimulation of relatively preserved prefrontal cognitive functions. Full behavioral remission in the long term was predicted by better working memory abilities. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 03/2015; 30(5). DOI:10.1002/mds.26160 · 5.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Swallowing disturbances are an important issue in Parkinson’s disease (PD) as several studies have shown that they are associated with increased risk of aspiration pneumonia and mortality. Information about factors related to swallowing disturbances, such as disease duration, age at assessment and concomitant dementia, is limited and would be useful for their management. Methods All consecutive out-patients evaluated at a movement disorders clinic (Parkinson Institute, Milan) over a 7-year period (2007-2014), meeting the UK Brain Bank criteria for idiopathic PD, were included in the present cross-sectional retrospective study. Presence of symptomatic swallowing disturbances was assessed using the specific item of the Non Motor Symptom Questionnaire. Results In the whole PD population (N=6,462), prevalence of symptomatic swallowing disturbances was 11.7% (95%CI, 10.9-12.5). Multivariable logistic regression analysis (adjusted for education) disclosed a significant interaction between disease duration and gender (P=0.009). In both gender strata, swallowing disturbances were significantly associated with longer disease duration and dementia (P<0.001 for all). A significant effect for age at assessment was also found in male patients. In non-demented patients, swallowing disturbances were associated with male gender, age and disease duration (P<0.02 for all). In demented patients an association was found only with male gender (P=0.018) and disease duration (P<0.001). Conclusions Gender, age, disease duration and dementia all seem to contribute to the occurrence of swallowing disturbances independently. However, the role played by these factors in sub-groups of patients stratified by gender and concomitant dementia suggests that swallowing disturbances are likely related to different neuro-degenerative patterns within the brain. The underlying mechanisms deserve further investigation.
    Parkinsonism & Related Disorders 10/2014; 20(12). DOI:10.1016/j.parkreldis.2014.09.031 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background A very limited number of studies report data on the clinical features of Parkinson's disease (PD) 20 years after onset and beyond. Objective To characterise PD 20 years after onset, investigating the impact of age at onset and disease duration on the clinical picture and the predictors of outcomes in patients reaching the 20-year time point. Methods We conducted a retrospective, cross-sectional study and a longitudinal study. All case visits of patients with a disease duration ≥20 years (N=401) were stratified by disease duration (20–22, 23–25, ≥26 years) and by age at onset (cut-off, 50 years). Patients with a disease duration of 20–22 years (N=320) were prospectively followed up for a median of 45 months (IQR 23–89) for the new occurrence of fracture, percutaneous endoscopic gastrostomy, institutionalisation, confinement to a wheelchair or bed and death. Results Older age at onset and longer disease duration were independently associated with a higher prevalence of major motor and non-motor milestones of disease disability (no interaction observed). In the longitudinal study, the most frequent outcomes were death (N=92), confinement to a wheelchair or bed (N=67) and fracture (N=52). Mortality was associated with the gender: male, older age, dysphagia, orthostatic hypotension, postural instability, fractures and institutionalisation. Fracture was associated with postural instability. Predictors of permanent confinement to a wheelchair or bed were older age, postural instability and institutionalisation. Comorbid dementia at the 20-year examination did not predict any of the outcomes. Conclusions Age at onset and disease duration are independent determinants of the clinical features of PD beyond 20 years. Non-motor symptoms depend more on age at onset rather than the disease duration itself. Non-levodopa-responsive axial symptoms are the main predictors of all relevant outcomes.
    Journal of Neurology Neurosurgery & Psychiatry 10/2014; 86(8). DOI:10.1136/jnnp-2014-308786 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Age is considered an important risk factor for Parkinson’s disease (PD). However, although life-expectancy has increased considerably, incidence rates of PD appeared to be stable over the last two decades. Accordingly, an increase in mean age at onset over time could be expected. We investigated the changes in age at onset in PD over the last two decades. Methods All consecutive PD patients assessed over a 18-year period (1995-2013) in a single tertiary outpatient clinic were included in the present retrospective cohort study. Results After adjusting for several confounders (gender, positive family history for PD, education, smoking at onset and past exposure to environmental/occupational pollutants), 5-year cohorts of year of disease onset were associated with increasing age at onset in both prevalent (N=6996) and incident (N=4172) cases (for trend, P<0.001). From 1995-2000 to 2010-2013 there was an increase in predicted age of 4.1 years (95%CI, 3.0-5.2) and 3.9 years (95%CI, 2.7-5.1) in prevalent and incident cases, respectively. However, the change in predicted age at PD onset, across cohorts of year at onset, showed a steeper increase than the corresponding sex and cohort-matched mean age from the official Italian statistics. Conclusions Over the last two decades, age at onset of PD appeared to shift progressively towards more advanced age. However, sequential, high quality population-based incidence studies are required. to establish whether there is a trend towards increase in age at onset over and above general population ageing and to assess whether the increase is associated with the improvement in medical and socio-economic conditions.
    Parkinsonism & Related Disorders 09/2014; 20(11). DOI:10.1016/j.parkreldis.2014.08.017 · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The relative risk of developing idiopathic PD is 1.5 times greater in men than in women, but an increased female prevalence in LRRK2-carriers has been described in the Ashkenazi Jewish population. We report an update about the frequency of major LRRK2 mutations in a large series of consecutive patients with Parkinson’s disease (PD), including extensive characterization of clinical features. In particular, we investigated gender-related differences in motor and non-motor symptoms in the LRRK2 population. Methods 2,976 unrelated consecutive Italian patients with degenerative Parkinsonism were screened for mutations on exon 41 (G2019S, I2020T) and a subgroup of 1,190 patients for mutations on exon 31 (R1441C/G/H). Demographic and clinical features were compared between LRRK2-carriers and non-carriers, and between male and female LRRK2 mutation carriers. Results LRRK2 mutations were identified in 40 of 2,523 PD patients (1.6%) and not in other primary parkinsonian syndromes. No major clinical differences were found between LRRK2-carriers and non-carriers. We found a novel I2020L missense variant, predicted to be pathogenic. Female gender was more common amongst carriers than non-carriers (57% vs. 40%; p=0.01), without any gender-related difference in clinical features. Family history of PD was more common in women in the whole PD group, regardless of their LRRK2 status. Conclusions PD patients with LRRK2 mutations are more likely to be women, suggesting a stronger genetic load compared to idiopathic PD. Further studies are needed to elucidate whether there is a different effect of gender on the balance between genetic and environmental factors in the pathogenesis of PD.
    Parkinsonism & Related Disorders 08/2014; 20(8). DOI:10.1016/j.parkreldis.2014.04.016 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We analysed the DJ1 gene in a large consecutive series (N=163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ≤40 years of age) patients and 100 healthy controls (mean age 64±7ys). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified.
    Neuroscience Letters 10/2013; 557(PB). DOI:10.1016/j.neulet.2013.10.048 · 2.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have reported that patients with Parkinson's disease (PD) have a favorable cardiometabolic risk profile. The aim of this study was to investigate the relationship between cardiometabolic risk factors and the duration of disease. One hundred and fifty patients with PD (56.7% men) were studied, measuring body mass index (BMI), waist circumference (WC), body fat percentage (BF%) by impedance, fasting glucose, serum lipids, and transaminases. In sex- and age-adjusted correlation models, duration of PD was inversely related to BMI (r = -0.20; P < 0.05) and BF% (r = -0.29; P < 0.005). Using multivariable regression models (adjustments: age, gender, smoking status, levodopa dose and, alternatively, BMI, WC, or BF%), high-density lipoprotein (HDL) levels were positively correlated with disease duration (P < 0.01 for all). In models adjusted for WC and BF%, total HDL-cholesterol ratio was also inversely associated with duration of PD (P < 0.05 for both). No other association between biochemical variables and the duration of PD was found. Moreover, no dose-response effect of levodopa on metabolic risk factors was observed. HDL levels and total HDL-cholesterol ratio were favorably associated with duration of PD. This factor may contribute to cardiometabolic protection in PD. The mechanisms underlying this association deserve further investigation.
    Nutrition 09/2013; 29(11-12). DOI:10.1016/j.nut.2013.04.013 · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome. METHODS: In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005-2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded. RESULTS: Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment. CONCLUSIONS: Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.
    Journal of neurology, neurosurgery, and psychiatry 04/2013; 85(3). DOI:10.1136/jnnp-2012-303988 · 5.58 Impact Factor
  • Clinical Nutrition Supplements 09/2012; 7(1):173. DOI:10.1016/S1744-1161(12)70427-1
  • Source
    Acta Neuropathologica 05/2012; 123(6):901-3. DOI:10.1007/s00401-012-0991-7 · 10.76 Impact Factor
  • Parkinsonism & Related Disorders 01/2012; 18:S37-S38. DOI:10.1016/S1353-8020(11)70225-5 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Neurobiology of aging 11/2011; 32(11):1994-2005. DOI:10.1016/j.neurobiolaging.2009.12.016 · 4.85 Impact Factor
  • Movement Disorders 09/2011; 26(11):2144-5. DOI:10.1002/mds.23807 · 5.68 Impact Factor
  • Annals of Neurology 03/2010; 67(3):411-2; author reply 412. DOI:10.1002/ana.21964 · 11.91 Impact Factor
  • Gianni Pezzoli · Michela Zini
    [Show abstract] [Hide abstract]
    ABSTRACT: Levodopa is the mainstay of symptomatic treatment for Parkinson's disease (PD). Although other treatments have been developed in the last 30 years, most patients use levodopa in view of its superior efficacy in controlling PD symptoms. Unfortunately, levodopa is associated with long-term motor complications (motor fluctuations and dyskinesias). The main causes of these undesirable effects are the narrowing of the therapeutic window with the natural progression of the disease, pulsatile dopaminergic stimulation due to the short half-life of the drug and erratic absorption. Several studies suggest that PD control could be enhanced by changing the mode of levodopa delivery so as to ensure continuous and stable supply of the drug to the brain. The objective of this text is to review the ascertained strengths and limitations of levodopa in PD, starting from its history, and propose novel modes of usage designed to cover currently unmet medical needs. Medline literature search (from 1973 to date). A perspective on the evolution of PD pharmacological treatment. Levodopa still is the best treatment for PD. Truly stable and controlled formulations that ensure clinical response should be developed to reduce the undesirable effects that restrict its efficacy.
    Expert Opinion on Pharmacotherapy 03/2010; 11(4):627-35. DOI:10.1517/14656561003598919 · 3.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The alpha-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson Disease (PD): triplication is associated with early-onset rapidly progressing parkinsonism with a strong likelihood of developing dementia, while duplication is associated with a less severe phenotype similar to idiopathic PD. We tested for SNCA multiplication 144 unrelated PD patients with a dominant family history. We identified one patient with SNCA duplication (0.7%). The SNCA-duplicated patient was a woman of 45 years of age with PD onset at 41 years of age. She experienced a rapidly progressive disease with early motor complications (on/off fluctuations and dyskinesias). Medical records confirmed that the proband's mother developed PD at 47 years of age and died at 63 with dementia. She experienced rapid progression in both motor and cognitive symptoms: development of dementia at 54 years of age, 7 years after onset. Although SNCA duplication is an unusual cause of familial PD testing for it is worthwhile. The clinical presentation of duplicated cases may be more aggressive than usual.
    Parkinsonism & Related Disorders 10/2009; 16(3):228-31. DOI:10.1016/j.parkreldis.2009.09.008 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.
    BMC Medicine 12/2008; 6(1):32. DOI:10.1186/1741-7015-6-32 · 7.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8.2%) had homozygous or compound heterozygous point mutations and/or exon rearrangements, while a single mutation was found in four subjects (2.7%). We identified eight exon rearrangements and nine point mutations, two of which were novel: c.735delT (p.C212/X224) and c.815C>G (p.C238W). Genotype-phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.
    Parkinsonism & Related Disorders 05/2008; 14(4):326-33. DOI:10.1016/j.parkreldis.2007.10.003 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report the results of a family-based study of LRRK2 G2019S penetrance in Parkinson disease. We studied 19 families identified through the analysis of unrelated consecutive patients. The cumulative incidence of the disease was 15% at 60 years, 21% at 70 years, and 32% at 80 years. This study provides accurate estimates of G2019S penetrance by minimizing the selection bias.
    Neurology 05/2007; 68(14):1141-3. DOI:10.1212/01.wnl.0000254483.19854.ef · 8.30 Impact Factor