Head trauma and Parkinson's disease: results from an Italian case-control study.

We evaluated the possible association between head trauma and Parkinson's disease (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson) study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Cases and controls were enrolled from six movement disorders centers located in the Central-Southern Italy. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Positive history of head trauma was considered only if the head trauma preceded the onset of PD. All cases and controls underwent a standard neurological examination. Adjusted ORs and 95% CI were estimated using multivariate analysis (logistic regression). Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. A positive history for head trauma was reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls. Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking, and alcohol consumption) showed a significant positive association between PD and head trauma with an adjusted OR of 1.50 (95%CI 1.04-2.17; p value 0.03). In agreement with literature data, our study supports the positive association between head trauma and PD.

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.

Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache. Although the mode of transmission is controversial, population-based and twin studies have implicated genetic factors, especially in migraine with aura. Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481). Functional data indicate that the putative pathogenetic mechanism is triggered by a loss of function of a single allele of ATP1A2. This is the first report associating mutations of Na+K+ pump subunits to genetic diseases.

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.

Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders.

Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score ≤ 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score ≤ 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p ≤ 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (ß ≤ -0.16) and age with all FAB items but prehension behavior (ß ≤ -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (ß = -0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients.

Wine drinking and essential tremor: a possible protective role.

The purpose of this study was to evaluate the possible association of cigarette smoking, coffee drinking, and wine consumption with essential tremor using a matched case-control design. Cases and controls were enrolled from 6 Movement Disorder centers in central-southern Italy. Essential tremor was diagnosed according to Bain's criteria. Three unrelated healthy controls (not affected by neurological disorders) per each enrolled case, matched by sex and age (± 5 years), were selected. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. All cases and controls underwent a standard neurological examination. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression for the matched cases and controls. Eighty-three patients with essential tremor (38 men and 45 women; mean age, 68.2 ± 8.6 years) and 245 matched control subjects (113 men and 132 women; mean age, 68.4 ± 9.7 years) were enrolled in the study. Multivariate analysis showed a significant negative association between essential tremor and wine consumption preceding the onset of disease (adjusted odds ratio, 0.23; 95% confidence interval, 0.08-0.64; P = .0005) with a significant dose effect (1-2 glass of wine per day: odds ratio, 0.32; 95% confidence interval, 0.10-0.95; P = .04; more than 3 glass of wine per day: odds ratio, 0.14; 95% confidence interval, 0.03-0.62; P = .01). In our sample no association between essential tremor and cigarette smoking or coffee drinking was found. Our data suggest a negative association between wine drinking and essential tremor, which could be explained by the long-term neuroprotective effect of its antioxidant components.

Reproductive factors and Parkinson's disease: a multicenter case-control study.

BACKGROUND: The objective of this study was to evaluate the possible association between endogenous and exogenous estrogens and Parkinson's disease (PD). METHODS: The FRAGAMP study is a large Italian multicenter case-control study. PD was diagnosed according to Gelb's criteria. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Adjusted ORs and 95% CIs were estimated using multivariate analysis (logistic regression). RESULTS: Two hundred PD women (mean age, 68.0 ± 9.5 years) and 299 control women (mean age, 61.8 ± 9.9 years) were enrolled in the study. Age at menarche, age at menopause, fertile life duration, cumulative duration of pregnancies, hormone replacement therapy, and surgical menopause were not significantly associated with PD. Multivariate analysis showed a significant positive association between use of oral contraceptives and PD, with an adjusted OR of 3.27 (95% CI, 1.24-8.59; P = .01). CONCLUSIONS: Our data suggest that oral contraceptives could increase the risk of PD.

Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort.

BACKGROUND: Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes. OBJECTIVES: To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients. METHODS: A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria. RESULTS: Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age ± SD 65.6 ± 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)]. CONCLUSIONS: Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD.

Voluptuary habits and clinical subtypes of Parkinson's disease: the FRAGAMP case-control study.

We evaluated the possible association between smoking, coffee drinking, and alcohol consumption and Parkinson's disease (PD). The FRAGAMP study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Adjusted ORs were estimated using unconditional logistic regression. Smoking, coffee, and alcohol consumption were also considered as surrogate markers of lifestyle and analysis was carried out considering the presence of at least one, two, or three factors. This latter analysis was separately performed considering Tremor-Dominant (TD) and Akinetic-Rigid (AR) patients. Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. Multivariate analysis showed a significant negative association between PD and cigarette smoking (OR 0.51; 95%CI 0.36-0.72), coffee drinking (OR 0.61; 95%CI 0.43-0.87) and wine consumption (OR 0.62; 95%CI 0.44-0.86); a significant trend dose-effect (P < 0.05) has been found for all the factors studied. We have also found a trend dose-effect for the presence of at least one, two or three factors with a greater risk reduction (83%) for the presence of three factors. However, a different strength of association between TD and AR was found with a greater risk reduction for the AR patients. We found a significant inverse association between PD smoking, coffee, and alcohol consumption. When analysis was carried out considering the association of these factors as possible surrogate markers of a peculiar lifestyle the association was stronger for the AR phenotype.

The FRAGAMP study: environmental and genetic factors in Parkinson's disease, methods and clinical features.

The Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson (FRAGAMP) study is a multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in Parkinson's disease (PD). Cases and controls were enrolled from five Movement Disorder centers in Central-Southern Italy. PD was diagnosed according to Gelb's criteria while the control groups consisted of the spouses of the enrolled patients or of healthy controls matched by age and area of residence. Cases and controls underwent a standardised questionnaire and a blood sample was taken for molecular analyses. At the end of the study 585 cases and 481 control subjects (287 spouse-controls and 194 generic-controls) were enrolled. Patients had a Hoehn-Yahr score of 2.3 +/- 0.8; 85% of them took levodopa and 47% had motor complications. The FRAGAMP study represents one of the largest case-control studies carried out in Europe to investigate the possible role of environmental and genetic factors in PD.

The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.

We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.

MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy.

PURPOSE: To prospectively assess sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) for differentiating progressive supranuclear palsy (PSP) from Parkinson disease (PD) and Parkinson variant of multiple system atrophy (MSA-P), with established consensus criteria as reference standard. MATERIALS AND METHODS: All study participants provided informed consent; study was approved by the institutional review board. Pons area, midbrain area, MCP width, and SCP width were measured in 33 consecutive patients with PSP (16 possible, 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 healthy control participants on T1-weighted MR images. The pons area-midbrain area ratio (P/M) and MCP width-SCP width ratio (MCP/SCP) were also used, and an index termed MR parkinsonism index was calculated [(P/M).(MCP/SCP)]. Differences in MR imaging measurements among groups were evaluated with Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction. RESULTS: Midbrain area and SCP width in patients with PSP (23 men, 10 women; mean age, 69.3 years) were significantly (P < .001) smaller than in patients with PD (62 men, 46 women; mean age, 65.8 years), patients with MSA-P (five men, 14 women; mean age, 64.0 years), and control participants (25 men, 25 women; mean age, 66.6 years). P/M and MCP/SCP were significantly larger in patients with PSP than in patients in other groups and control participants. All measurements showed some overlap of values between patients with PSP and patients from other groups and control participants. MR parkinsonism index value was significantly larger in patients with PSP (median, 19.42) than in patients with PD (median, 9.40; P < .001), patients with MSA-P (median, 6.53; P < .001), and control participants (median, 9.21; P < .001), without overlap of values among groups. No patient with PSP received a misdiagnosis when the index was used (sensitivity and specificity, 100%). CONCLUSION: The MR parkinsonism index can help distinguish patients with PSP from those with PD and MSA-P on an individual basis.

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease.

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA-P in order to evaluate its differential diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 x 10(-3)mm(2)/s) than patients with PD (median 0.79 x 10(-3) mm(2)/s, P < 0.001), MSA-P (median 0.79 x 10(-3) mm(2)/s, P < 0.001), and healthy controls (median 0.80 x 10(-3) mm(2)/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA-P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms.

The arginine growth hormone stimulation test in bradykinetic-rigid parkinsonisms.

The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in distinguishing between PSP, MSA-P, and PD. We measured the GH response to arginine in serum samples of 26 MSA-P, 23 PSP, and 26 PD patients, and in 80 healthy controls. We used ANOVA followed by the Bonferroni test to compare GH values and peaks among groups. We used receiver operating characteristic curve analysis to establish the arginine cut-off level that best differentiated between MSA-P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA-P (1.46 +/- 0.29 microg/L) than in both PD (8.74 +/- 0.98 microg/L) and PSP (6.64 +/- 0.82 microg/L) patients, and controls (8.59 +/- 0.44 microg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut-off level of 4 microg/L, arginine test distinguished MSA-P from PD with a sensitivity of 92% and a specificity of 96%, and MSA-P from PSP with a sensitivity of 78% and a specificity of 96%. The GH response to arginine differentiates MSA-P from PD and PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of PSP patients differed from that of MSA-P patients, but was not identical to that of normal controls and PD patients. Our results suggest that the impairment of the central mechanisms modulating GH release differs between PSP and MSA-P.

Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson's disease.

Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK1, and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in 1 of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK1 mutations, in 3 of the 6 unrelated patients with Gly2019Ser mutation in the LRRK2 gene, whereas it was impaired in all patients with idiopathic PD. MIBG was preserved in all control subjects. Our study shows that myocardial MIGB uptake was normal in 8 of 14 patients with genetic PD, suggesting that cardiac sympathetic denervation occurs less frequently in genetic PD than in idiopathic PD. Our findings also demonstrate that MIGB uptake has a heterogeneous pattern in genetic PD, because it was differently impaired in patients with different mutations in the same gene or with the same gene mutation.

Prescribing pattern of anti-Parkinson drugs in Southern Italy: cross-sectional analysis in the years 2003-2005.

Aim of this study was to evaluate prevalence of use and prescribing pattern of Anti-Parkinson Drugs (APDs) in general practice of Southern Italy. Among 120,000 individuals registered in the lists of 93 general practitioners of Southern Italy, we estimated one-year prevalence and incidence of APD use in the years 2003-2005. Overall, prevalence of APD use remained stable over the years and it strongly increased in subjects over 70 years of age. L-Dopa with a dopa decarboxylase inhibitor was the most frequently prescribed APD, although the use of both ergot and non-ergot derivative DAs has increased, particularly, in the elderly. A high proportion of APD users (15-20%) received only one prescription during the study period.

Hormonal replacement therapy in women with Parkinson disease and levodopa-induced dyskinesia: a crossover trial.

Eleven postmenopausal women with Parkinson disease and levodopa-induced peak-dose dyskinesias underwent a double-blind, placebo-controlled, crossover study. The active treatment consisted of estrogen replacement therapy for 12 weeks, followed by medroxyprogesterone acetate for 2 weeks. Estrogen replacement therapy-medroxyprogesterone acetate administration significantly improved peak-dose dyskinesia without worsening motor disability, thus suggesting a possible benefit on dyskinesias in postmenopausal women with Parkinson disease.

Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson's disease and progressive supranuclear palsy.

Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) from Parkinson's disease is difficult in the early stage of the disease. In order to identify objective markers for differential diagnosis, we studied these three groups of patients with diffusion-weighted MRI (DWI). Sixteen MSA-P patients, 16 with PSP, 16 with Parkinson's disease and 15 healthy volunteers were studied. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, thalamus, white matter, pons and middle cerebellar peduncles (MCPs). rADC calculated in the MCP completely differentiated MSA-P patients (median: 0.93 x 10(-3) mm2/s) from PSP patients (median: 0.82 x 10(-3) mm2/s, P < 0.001), Parkinson's disease patients (median: 0.79 x 10(-3) mm2/s, P < 0.001) and healthy volunteers (median: 0.81 x 10(-3) mm2/s, P < 0.001). Other regions considered showed an overlapping among groups. DWI discriminates MSA-P from PSP and Parkinson's disease and healthy volunteers on the basis of MCP rADC values. These in vivo results confirm the pathological findings that the majority of MSA-P patients have moderate or severe degenerative changes not only in the nigrostriatal but also in the olivopontocerebellar systems. Our findings indicate that, in order to substantially contribute to the in vivo differential diagnosis of MSA-P, PSP and Parkinson's disease, rADC measurements should not be limited to the basal ganglia but should also include the MCP.

How many parkinsonian patients are suitable candidates for deep brain stimulation of subthalamic nucleus? Results of a questionnaire.

We used a CAPSIT-based questionnaire to estimate the percentage of parkinsonian patients suitable for subthalamic nucleus (STN) deep brain stimulation (DBS) in a movement disorders clinic. We found that out of 641 consecutive PD patients only 1.6% fulfilled strict STN-DBS criteria. When we applied more flexible criteria, the percentage of eligibility increased to 4.5%. Most patients (60%) were ineligible because they did not satisfy multiple questionnaire items. Items related to disease severity were responsible for the largest number of exclusions. This knowledge will help make decisions on resource allocation in centres wishing to start DBS surgery.

Pramipexole versus sertraline in the treatment of depression in Parkinson's disease: a national multicenter parallel-group randomized study.

In addition to treating the motor symptoms of Parkinson's disease, the dopamine agonist pramipexole has shown an antidepressant effect. The trials, however, included patients with motor complications, raising the question of whether the antidepressant benefit represented only a treatment-related motor improvement. To address this issue, we have conducted a 14-week randomized trial comparing pramipexole with an established antidepressant in patients without motor complications. At seven Italian centers, 67 Parkinsonian outpatients with major depression but no history of motor fluctuations and/or dyskinesia received open-label pramipexole (at 1.5 to 4.5 mg/day) or sertraline (at 50 mg/day). In both groups, the Hamilton Depression Rating Scale (HAM-D) score decreased throughout 12 weeks of treatment, but in the pramipexole group the proportion of patients who recovered, as defined by a final HAM-D score