Effects of immediate thrombolytic treatment in imaging area on functional outcome in patients with acute ischemic stroke.

INTRODUCTION: Door-to-needle time (DNT) is an established predictor of outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Several strategies have been proposed to streamline in-hospital pathways, among which treatment at CT/MR bed. AIM: To explore the impact of treatment at CT/MR bed, here defined as imaging area (IA), on functional outcome in stroke patients treated with IVT alone. METHODS: All AIS patients treated with IVT alone at our center in 2020, 2021, and 2022 were included. Patients with any previous disability were excluded. The cohort was divided into two groups, depending on the treatment site. One group received IVT at IA, the other at emergency room or stroke unit (non-IA). Regression analysis assessed the association between treatment site and 3-month outcome. RESULTS: A total of 327 patients who received IVT alone were included in the analysis. One hundred thirty-three (40.7%) were in the IA group and 194 (59.3%) in the non-IA group. The groups showed similar baseline characteristics. In the IA group, DNT was 45 min shorter. Despite similar rates of functional independence (mRS 0-2), the IA group showed higher rates of excellent outcome (mRS 0-1) compared to the non-IA group (60.1% vs 42.8%, p<0.01). Immediate treatment at IA was independently associated to excellent outcome (OR 1.78 [1.03-3.08]). CONCLUSIONS: Thrombolytic treatment at IA lowers DNT and is an independent predictor of excellent outcome after AIS. Our study emphasizes the importance of immediate thrombolytic treatment at IA, soon after radiological eligibility is confirmed. Immediate treatment at IA should be a standard-of-care for AIS.

Humoral efficacy of the third SARS-CoV-2 vaccine dose in Multiple Sclerosis subjects undergoing different disease-modifying therapies.

BACKGROUND: It remains unclear how vaccine doses and combinations of vaccination and infection affect the magnitude and quality of immune responses, particularly against novel SARS-CoV-2 variants in subjects with immune-related disorders, such as people with multiple sclerosis (pwMS). Several studies have evaluated the duration of anti-SARS-CoV-2 immune protection in healthy individuals; however clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in pwMS receiving disease-modifying therapies (DMTs). METHODS: In this prospective study, we evaluated the humoral response to the third (3rd) BNT162b2 vaccine (booster) dose in a monocentric cohort of pwMS undergoing eight different DMTs, all without previous SARS-CoV-2 infection. Quantitative determination of SARS-CoV-2 IgG Spike titre was carried out by anti-SARS-CoV-2 S assay in 65 pwMS and 9 healthy controls, all without previous SARS-CoV-2 infection. Moreover, these measurements were also compared to their relative levels at 21 days (T1) and ∼6 months (T2) after the second (2nd) vaccination. RESULTS: We observed that the humoral response to the booster dose in Interferon ß-1a-, Dimethyl fumarate- and Teriflunomide-treated pwMS is comparable to healthy controls, while increased in Cladribine-treated pwMS. Additionally, the 3rd dose elicits a seroconversion in the 100% of pwMS under Fingolimod and in the 65% of those under Ocrelizumab. Moreover, multivariate regression analysis showed that treatment with Interferon ß-1a, Dimethyl fumarate and Cladribine positively associates with an increased humoral response. CONCLUSIONS: Taken together this evidence strongly indicates the importance of the booster dose to enhance SARS-CoV-2-specific immunity especially in immunocompromised subjects, such as pwMS under DMTs.

Interferon Beta-1a treatment promotes SARS-CoV-2 mRNA vaccine response in multiple sclerosis subjects.

BACKGROUND: Several concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection. METHODS: We collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs. Sera were tested using the Elecsys anti-SARS-CoV-2-IgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titres from MS subjects were compared with 24 age- and sex-matched healthy controls (HC). Percentage and absolute number of B and T lymphocytes were evaluated by cytofluorimetric analysis in the same study cohort. RESULTS: When compared with SARS-CoV-2 IgG levels in HC (n = 24, median 1089 (IQR 652.5-1625) U/mL), we observed an increased secretion of SARS-CoV-2 IgG in interferon-beta 1a (IFN)-treated MS subjects (n = 22, median 1916 (IQR 1024-2879) U/mL) and an impaired humoral response in MS subjects undergoing cladribine (CLAD) (n = 10, median 396.9 (IQR 37.52-790.9) U/mL), fingolimod (FTY) (n = 19, median 7.9 (IQR 4.8-147.6) U/mL) and ocrelizumab (OCRE) (n = 15, median 0.67 (IQR 0.4-5.9) U/mL) treatment. Moreover, analysis of geometric mean titre ratio (GMTR) between different DMT's groups of MS subjects revealed that, when compared with IFN-treated MS subjects, intrinsic antibody production was impaired in teriflunomide (TERI)-, natalizumab (NAT)-, CLAD-, FTY- and OCRE-, while preserved in DMF- and GA-treated MS subjects. CONCLUSION: Humoral response to BNT162b2-mRNA-vaccine was increased in IFN-treated MS subjects while clearly blunted in those under CLAD, FTY and OCRE treatment. This suggests that the DMTs could have a key role in the protection from SARS-CoV-2 related disease and complication in MS subjects, underlying a novel aspect that should be considered in the selection of the most appropriate therapy under COVID-19 pandemic.

A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.

INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment. OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment. METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression. RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment. CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.

Interoceptive processing deficit: A behavioral marker for subtyping Parkinson's disease.

BACKGROUND: Non-motor symptoms in Parkinson's disease (PD), such as cognitive, emotional, autonomic and somatosensory alterations, are not ubiquitous but vary between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes of the syndrome. Non-motor phenomena (e.g., anxiety, depression and apathy) have been related to representation of autonomic and somatosensory sensations (interoception), and recent findings suggest interoceptive deficits in PD. OBJECTIVES: To test whether interoceptive processing is differently affected in TD and PIGD phenotypes, by assessing both interoceptive accuracy and sensibility in PD patients with TD and PIGD subtypes, and in healthy controls. METHODS: Interoceptive accuracy was measured by the heartbeat perception task requiring participants to count their own heartbeats in a given time interval. A time-estimation, control task was also administered asking participants to count the seconds in a set period of time. Interoceptive sensibility was assessed by a questionnaire of subjective interoception. Finally, the patients underwent measures of anxiety, depression, apathy and anhedonia, and impulsive-compulsive disturbances. RESULTS: The main results showed reduced interoceptive accuracy and sensibility in TD patients relative to both PIGD patients and healthy controls. Reduced interoceptive accuracy of TD group was a reliable result since their performance on the time estimation control task was comparable to that of both PIGD patients and healthy controls. CONCLUSIONS: These findings demonstrate that the behavioural assessment of different aspects of interoceptive processing can provide with a further marker for subtyping patients with PD.

Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD. METHODS: Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied. RESULTS: Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8. CONCLUSIONS: The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD.

Assessment of apathy minimising the effect of motor dysfunctions in Parkinson's disease: a validation study of the dimensional apathy scale.

PURPOSE: Apathy is associated with motor symptoms in Parkinson's disease (PD); therefore, its evaluation could be influenced by motor disability. The Dimensional Apathy Scale (DAS) evaluates apathy excluding confounding effects of motor symptoms. The present study had three major aims: (a) to explore the psychometric properties of the DAS in non-demented PD patients; (b) to determine an optimal cut-off score of the DAS to identify apathetic PD patients; and (c) to determine a specific apathy profile in PD patients as compared to healthy controls (HC). METHODS: One hundred and seven PD patients and 100 HC completed the DAS. To explore convergent and divergent validity of the DAS in PD, patients underwent the Apathy Evaluation Scale and tools for assessing depressive symptoms, anxiety and cognition. Clinical aspects were recorded. Receiver operating characteristic curve analyses were carried out to estimate the optimal cut-off score to identify clinically significant apathy. RESULTS: The DAS scores showed high internal consistency and good evidence for convergent and discriminant validity. Maximum discrimination between apathetic and non-apathetic patients was obtained with a cut-off score of 28.5 (total score range: 0-72 with higher score indicating more severe apathy). Comparison between PD and HC groups revealed significant differences on total DAS, behavioural/cognitive initiation and emotional subscales. CONCLUSIONS: The DAS is a valid and reliable tool to assess multidimensional apathy in PD, independently of severity of motor symptoms. Reduced initiation of thought and behaviour and emotional blunting characterised PD patients, without confounding effects of motor disability.

Caffeine consumption and the 4-year progression of de novo Parkinson's disease.

INTRODUCTION: Higher caffeine consumption has been associated with reduced risk of Parkinson's disease (PD), and with a more benign progression of motor and non-motor symptoms (NMS). The present observational cohort study investigated motor and non-motor correlates of caffeine consumption in de novo PD. METHODS: 79 newly diagnosed, drug naïve PD patients have been included and followed up for 4 years. The total caffeine use was calculated with the Caffeine Consumption Questionnaire. Following study variables were recorded at baseline, and after 2 and 4 years: UPDRS part III, UPDRS part IV, l-dopa Equivalent Daily Dose (LEDD), NMS Questionnaire (NMSQuest), and the time occurring from PD diagnosis to the need for l-dopa treatment. Age, gender and disease duration were included as covariates in the statistical models. RESULTS: The average daily caffeine consumption was 296.1 ± 157.2 mg. At Cox regression models, higher caffeine consumption was associated with a lower rate of starting l-Dopa treatment (HR = 0.630; 95%CI = 0.382-0.996). At the mixed-effects linear regression models considering the whole study period, each additional espresso cup per day (50 mg of caffeine) was more likely associated with 5-point lower UPDRS part III total score (Coef = -0.01; 95%CI = -0.02 to 0.00), with 50% reduced LEDD (Coef = -0.01; 95%CI = -0.15 to 0.00; p = 0.021), and with 5-point lower NMSQuest total score (Coef = -0.01; 95%CI = -0.01 to 0.00), but not with UPDRS part IV total score (Coef = -0.00; 95%CI = -0.00 to 0.00). CONCLUSION: Caffeine consumption was associated with a reduced accrual of motor and non-motor disability during 4-year follow-up in de novo PD, highlighting the rationale for using adenosine A2A antagonists since the early phases of PD.

Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).

INTRODUCTION: Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients. METHODS: A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales. RESULTS: There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%). CONCLUSION: The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages.

Serum uric acid is associated with apathy in early, drug-naïve Parkinson's disease.

Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.

STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data. METHODS: One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability. RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88). CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.

Mild Cognitive Impairment in newly diagnosed Parkinson's disease: A longitudinal prospective study.

INTRODUCTION: In PD, Mild Cognitive Impairment (PD-MCI) occurs since early stages of disease. The aims were to assess presence of PD-MCI in untreated, drug-naive PD patients, and to follow-up the sample over 4 years to ascertain evolution of neurocognitive profile. METHODS: Seventy-six patients underwent neuropsychological testing at baseline (T0), and after 2 (T1:n = 62) and 4 years (T2:n = 55). Diagnosis of PD-MCI and PD-associated dementia (PDD) was made according to current consensus criteria. RESULTS: PD-MCI occurred in 25/76 patients (32.9%) at baseline, and 4 of them reverted from PD-MCI to Normal Cognition (Reverters), 7 remained stable (Non-Reverters) and 2 developed PDD at T2; 12 patients were lost to the follow-up. Among the 51 patients with normal cognition (PD-CN) at T0, 27 had normal cognition at T2 (5 of them were Reverters with respect to diagnosis at T1), 5 had MCI at T1 and T2 (Non-Reverters), 9 had MCI at T2 only, whereas 1 developed PDD; 9 patients were lost to the follow-up. At baseline, Reverters (n = 9) had younger age at onset and better performance on constructional visuospatial task than Non-Reverters (n = 12). Compared to patients without PD-MCI at all evaluations (n = 19), Reverters had poorer performance on verbal immediate recall and attention tasks and higher level of apathy at T0. Reduced performance on the Stroop Test at baseline predicted PD-MCI at T2. CONCLUSION: Executive dysfunctions predicted development of PD-MCI after few years from onset. Reversal from PD-MCI to PD-CN was related to young age at onset and high level of apathy at baseline evaluation.

Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients.

INTRODUCTION: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. METHODS: Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. RESULTS: PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. CONCLUSIONS: Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD.

Nonmotor predictors for levodopa requirement in de novo patients with Parkinson's disease.

The variability in the clinical phenotype of Parkinson's disease (PD) suggests the existence of several subtypes of the disease. Motor heterogeneity of PD is well established, but not nonmotor heterogeneity. At present, we are unable to predict the rate of progression of PD based on robust biomarkers. We aimed to examine the heterogeneity of PD by attempting to identify nonmotor factors associated with the rate of motor progression and functional decline, as measured by the time to reach the need for levodopa therapy during the first 4 years from diagnosis in a cohort of de novo PD patients. The median time to introduction of L-dopa for patients with urinary symptoms was significantly shorter than that for those without (20 vs. 37 months; P = 0.001). Cox's regression models showed that the urinary domain was associated with a higher probability of starting L-dopa (hazard ratio: 2.1; P = 0.002). There was no influence of such confounders as sex, age, baseline motor features, use of dopamine agonists and/or monoamine oxidase B inhibitors, and total L-dopa equivalent daily dosage. Patients with urinary symptoms had higher baseline and follow-up motor and nonmotor disturbances than those without. Our study suggests the existence of a subgroup of patients who show urinary symptoms along with an overall higher motor and nonmotor burden. Such patients are prone to manifest a rapid functional decline over the first 4 years of the disease. Urinary symptoms might be a clinical marker of severity as well as a possible nonmotor subtype of PD.

Quitting smoking: an early non-motor feature of Parkinson's disease?

INTRODUCTION: Epidemiological studies report a 60-70% reduced risk of Parkinson's disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated. METHODS: We recruited 116 de novo PD subjects, and investigated current, former and never smoking, and reasons for smoking cessation among former smokers. Two hundred and thirty-two controls were matched by Propensity Score. RESULTS: PD subjects and controls were found to be current smokers (7.7 vs. 39.6%), former smokers (43.9 vs. 6.5%) and never smokers (48.2 vs. 53.9%). Logistic regression showed that current smokers were less likely to have PD (p < 0.001; OR: 0.22; 95% CI: 0.10-0.46), while former smokers were more likely to have PD (p < 0.001; OR: 7.6; 95% CI: 4.09-15.75), as compared to never smokers. Fifty-one PD patients reported quitting smoking before PD diagnosis (mean time since cessation 9.4 ± 7.3 years). Most important reasons to quit smoking in PD group were illness different from PD (26 subjects, 51.0%), knowledge of the harmful effects of smoking (24 subjects, 47.0%), and physician's advice (1 subject, 2.0%). CONCLUSION: The reduced prevalence of current smokers among PD subjects as compared to healthy controls is consistent with previous findings, suggesting a possible neuroprotective effect of smoking. However, it could be due, at least in part, to the increased prevalence of former smokers among PD patients, that were more prone to quit smoking as compared to healthy controls. We suggest that smoking cessation could be an early preclinical condition occurring in PD.

Dopamine transporter availability in motor subtypes of de novo drug-naïve Parkinson's disease.

Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of Parkinson's disease associated with different disease progression and neurochemical/neuropathological features. The role of presynaptic nigrostriatal dopaminergic damage is still controversial, poorly explored, and only assessed in medicated patients. In this study, we investigated with FP-CIT SPECT the striatal dopamine transporter (DAT) availability in drug-naïve PD patients with ART and TD phenotypes. Fifty-one de novo, drug-naïve patients with PD underwent FP-CIT SPECT studies. Patients were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and TD (27/51) according to UPDRS part III. ART and TD patients were not different with regard to age, gender, and disease duration. However, compared to TD, ART patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007, respectively), whereas no differences were found in caudate. Moreover, in the whole group of patients, rigidity and bradykinesia, but not tremor scores of UPDRS part III were significantly related to FP-CIT binding in the putamen. These results suggest that in newly diagnosed drug-naïve PD patients DAT availability might be different between ART and TD in relation to different disease severity.

Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.

BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking. METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment. RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features. CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.

Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease?

BACKGROUND: Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored. METHODS: We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation. RESULTS: We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up. DISCUSSION: This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI.