Personality and psychopathological characteristics in functional movement disorders.

INTRODUCTION: Aim of the present study was to assess personality and psychopathological characteristics in patients with functional movement disorders (FMDs) compared to patients with other neurological disorders (OND). METHODS: In this cross-sectional study, patients affected by clinically established FMDs and OND who attended the Neurologic Unit of the University-Hospital "Policlinico-San Marco" of Catania from the 1st of December 2021 to the 1st of June 2023 were enrolled. Personality characteristics were assessed with the Rorschach test coded according to Exner's comprehensive system and the Structured Clinical Interview for DSM-5 (SCID-II). RESULTS: Thirty-one patients with FMDs (27 women; age 40.2±15.5 years; education 11.7±3.2 years; disease duration 2.3±2.5 years) and 24 patients affected by OND (18 women; age 35.8±16.3 years; education 11.9±2.9 years; disease duration 3.4±2.8 years) were enrolled. At the Rorschach, FMDs presented a significantly higher frequency of Popular (P) and sum of all Human content codes (SumH>5) responses and avoidant coping than OND. CONCLUSION: FMDs presented "conformity behaviors", excessive interest in others than usual a maladaptive avoidant style of coping and a difficulty in verbalizing emotional distress. These psychopathological characteristics may favor the occurrence of FMDs.

Exploring the knowledge, attitudes, and practices on sexual and gender minorities patients: a survey on Italian Neurologists.

BACKGROUND: Sexual and gender minorities (SGM) encompass individuals identifying as lesbian, gay, bisexual, transgender, and queer (LGBTQ). SGM patients experience difficulties in accessing healthcare and may face discrimination, impacting their overall health outcomes. Enhancing healthcare professionals' knowledge is the initial step in dismantling these barriers. MATERIALS AND METHODS: The study has been conducted on the neurologists of the Italian Society of Neurology (SIN). We utilized a survey instrument comprising 24 Likert-type questions to investigate knowledge, attitudes, and practices concerning sexual orientation and gender identity minorities. Likert scales were assessed with scores 1 and 2 as negative response, 3 as neutral, and 4 and 5 as positive responses. RESULTS: A total of 177 neurologists (103 women; 58.2%) participated, with a mean age of 44.3 ± 14.6 years answered the survey. Over half recognized sexual and gender orientation as social determinants of health, yet only a minority acknowledged the elevated prevalence of physical and mental health issues in SGM populations. Nearly, all respondents felt confident in examining a sexual minority patient, while only half felt the same regarding transgender patients. The majority of neurologists expressed a need for more comprehensive training and supervision in treating SGM patients. CONCLUSION: To enhance healthcare quality for SGM populations, healthcare professionals must receive appropriate training in how to approach, assess, and treat patients within this demographic.

Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights.

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD. METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT. RESULTS: Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs. CONCLUSIONS: Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD.

Neuroanatomical findings in isolated REM sleep behavior disorder and early Parkinson's disease: a Voxel-based morphometry study.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a parasomnia characterized by loss of physiological atonia of skeletal muscles with abnormal behaviors arising during REM sleep. RBD is often the early manifestation of neurodegenerative diseases, particularly alpha-synucleinopathies, such as Parkinson's disease (PD). Both structural and functional neuroimaging studies suggest that iRBD might share, or even precede, some of the features commonly found in PD, although without a definitive conclusion. Aim of the study is to evaluate the presence of structural abnormalities involving cortical and subcortical areas in PD patients with RBD and iRBD. Patients with video-polysomnographic (VPSG)-confirmed iRBD, and patients with a diagnosis of PD were recruited. In all PD patients, the presence of probable RBD was assessed during the follow-up visits (PD/pRBD). A group of healthy controls (HC) subjects was also recruited. Each subject underwent a structural brain MRI using a 3-D T1-weighted spoiled gradient echo sequence. Twenty-three patients with iRBD, 24 PD/pRBD, and 26 HC were enrolled. Voxel-based morphometry-AnCOVA analysis revealed clusters of grey matter changes in iRBD and PD/pRBD compared to HC in several regions, involving mainly the frontal and temporal regions. The involvement of cortical brain structures associated to the control of sleep cycle and REM stage both in PD/pRBD and iRBD might suggest the presence of a common structural platform linking iRBD and PD, although this pattern may not underlie exclusively RBD-related features. Further longitudinal studies are needed to clarify the patterns of changes occurring at different time points of RBD-related neurodegeneration.

Gender differences in non-motor fluctuations in Parkinson's disease.

Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21-8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF.

Brain linear measurements for differentiating normal pressure hydrocephalus from Alzheimer's disease: an exploratory study.

BACKGROUND AND PURPOSE: Easy and reliable tools for the differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) are needed. MATERIALS AND METHODS: In this cross-sectional study iNPH and AD patients referred to the Neurology Unit of the University of Catania from 1 January 2020 to 1 December 2022 were enrolled. The following brain linear measurements (BLMs) were calculated: Evan's index (EI), the parieto-occipital ratio (POR) and the temporal ratio (TR). For each index, sensitivity, specificity and the area under the curve (AUC) were calculated. Moreover, a cumulative index, the BLM index, was also considered. RESULTS: Fifty patients (25 iNPH and 25 AD) were enrolled. In differentiating iNPH from AD, EI had the highest AUC (0.956), POR had the highest specificity (100%) whilst TR had the highest sensitivity (92%). The BLM index differentiated iNPH and AD with a sensitivity of 96%, a specificity of 92% and an AUC of 0.963 with an optimal cut-off value of 0.303. CONCLUSION: Evan's index, POR and TR may be useful in the differential diagnosis between iNPH and AD. At an individual level, the BLM index represents a valid and reliable tool to achieve an accurate differentiation between these two conditions.

Influence of RBD onset on the clinical characteristics of Parkinson's disease patients: a retrospective study.

INTRODUCTION: In Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) might either precede the appearance of motor symptoms, or develop during the disease course. PD patients with RBD are characterized by a higher burden of cognitive impairment and hallucinations. However, few studies have analyzed the clinical characteristics of PD patients according to the timeline of RBD onset. METHODS: PD patients have been retrospectively enrolled. Presence and onset of probable RBD (pRBD) has been evaluated using RBD Screening Questionnaire (score ≥ 6). Presence of Mild Cognitive Impairment (MCI) at baseline has been evaluated using the MDS criteria level II. Presence of motor complications and hallucinations has been evaluated at a 5-year follow-up. RESULTS: A total of 115 PD patients (65 men, 56.5%; mean age 62.5 ± 9.7 years; mean disease duration 3.7 ± 3.9 years) have been enrolled. Out of these, 63 fulfilled the diagnosis of pRBD (54.8%) with 21 (33.3%) reporting the RBD onset before the onset of the motor symptoms (PD-RBDpre), and 42 (66.7%) after the motor symptoms (PD-RBDpost). At enrolment presence of MCI was associated with PD-RBDpre patients (OR 5.04; 95% CI 1.33-19.05; p value 0.02). At follow-up, a higher risk of developing hallucinations was also associated with PD-RBDpre (OR 4.68; 95% CI 1.24-17.63; p = 0.022). CONCLUSIONS: PD patients with RBD occurring before the onset of motor symptoms represent a subgroup of patients with a more severe cognitive phenotype and with a higher risk of developing hallucinations along the disease course, with significant implications in terms of prognostic stratification and therapeutic approach.

Turning and Sitting in Early Parkinsonism: Differences Between Idiopathic Normal Pressure Hydrocephalus Associated with Parkinsonism and Parkinson's Disease.

Background: Differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) associated with parkinsonism (iNPH-P) and Parkinson's disease (PD) may prove difficult when evaluating patients with early parkinsonism. The objective of this study was to evaluate differences in mobility during standardized tasks between iNPH-P and PD. Methods: We selected 21 iNPH-P and 21 pharmacologically untreated PD patients. They all performed the instrumented Timed Up and Go test at the time of diagnosis. Results: Turning tasks showed longer duration and lower speed in iNPH-P than in PD. Vertical variation in acceleration during the sit-to-stand phase was lower in iNPH-P patients, whereas the duration of the stand-to-sit phase was longer. On walking, iNPH-P showed smaller stride length and a longer gait cycle duration. In multivariate analysis adjusting for age and cognitive status as potential confounders, average angular speed on turning before sitting was the discriminating parameter between the two groups. Conclusions: Patients with iNPH-P showed specific abnormal mobility performances with respect to untreated PD, specifically during the turning-to-sitting transition.

Long-Duration Response to Levodopa, Motor Learning, and Neuroplasticity in Early Parkinson's Disease.

BACKGROUND: Long-duration response (LDR) to levodopa and motor learning could be involved in changes in neuroplasticity of cortical excitability in Parkinson's disease (PD). P300, motor evoked potentials (MEPs), and Bereitschaftspotential (BP) are neurophysiological surrogate markers of neuroplasticity. OBJECTIVE: We aimed to define in PD the effects of LDR and motor learning on neurophysiological parameters involved in neuroplasticity. METHODS: Drug-naive PD patients underwent a 15-day treatment with levodopa/carbidopa 250/25 mg daily. Achievement of LDR was assessed on the 15th day of treatment (T15). Patients were grouped based on the achievement of a sustained LDR (LDR+) or no LDR (LDR-) and to the assignment of a learning motor exercise (LME) or no motor exercise (NME). Patients underwent clinical and neurophysiological (P300, MEPs, and BP) assessments at baseline (T0) and on T15. RESULTS: Forty-one PD patients and 24 age- and sex-matched normal controls (NCs) were enrolled. Neurophysiological parameters differed between untreated PD patients and NCs. Four groups of patients were obtained at the end of treatments: trained patients with a sustained LDR (LDR + LME group), untrained patients with a sustained LDR (LDR + NME group), trained patients without LDR (LDR-LME group), and untrained patients without LDR (LDR-NME group). At baseline, no differences in clinical and neurophysiological parameters were evident among the groups. After the treatments, significant improvements in neurophysiological parameters were observed in the LDR + LME group. No modifications were found in the groups without LDR. CONCLUSIONS: The achievement of a sustained LDR may act synergistically with motor learning to induce adaptive changes in neuroplasticity in basal ganglia and cortical networks. Our findings support LDR as a pharmacological outcome possibly facilitating the action of motor learning on neuroplasticity in early PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Verbal Reasoning Impairment in Parkinson's Disease.

Background: The aim of this study was to assess verbal reasoning (VR) functioning in patients with Parkinson's disease (PD) and healthy controls (HCs). Methods: The non-demented PD patients and HCs matched by age and global cognition were enrolled in this study. VR was assessed with the verbal reasoning test (VRT), total score, and subsets. Results: Eighty-seven PD patients (51 men; mean age 63.8 ± 7.9 years) and 87 HCs (46 men; mean age 63.7 ± 8.0 years) were enrolled. At univariate analysis, PD patients presented a significantly lower score in the VRT subset classification (12.3 ± 2.1) than HCs (12.9 ± 1.7) with an odds ratio (OR) of 0.8 (95% confidence interval [CI] 0.70-0.98; p = 0.003). The strength of association was also confirmed at multivariate analysis (OR = 0.8, 95% CI 0.70-0.98; p = 0.003). Moreover, in PD patients, a statistically significant positive correlation was found between VRT-classification and MoCA scores (r = 0.330; p = 0.002). Conclusions: PD patients presented lower VR performance than HCs.

Corticobasal syndrome and Parkinson's disease at the beginning: asymmetrical patterns of MRI and Blink Reflex for early diagnosis.

Differential diagnosis between Parkinson's disease (PD) and corticobasal syndrome (CBS) could be challenging at the early stage, due to the asymmetric onset of both diseases. Despite the clinical overlap, the anatomical circuits involved in these disorders are different. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) and cortical thickness (CTh) in drug-naïve PD and CBS patients for characterizing pathophysiological mechanisms underlying these conditions. Patients with a clinically probable diagnosis of PD and possible CBS were recruited. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100-150-200-300-400-500-750 ms. Asymmetry index (AI) of R2BRRC for each ISI was computed. Patients underwent a structural brain MRI and hemisphere CTh and AI of MRI was calculated. Fourteen drug-naïve PD patients and 10 patients with early CBS diagnosis were enrolled. R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100 and 150 ms (p < 0.001) compared to most affected side (MAS), whereas no differences between LAS and MAS were found in CBS. AI of R2BRRC at ISI-100 ms showed significant difference, being higher in PD. CTh analysis showed significant differences between groups in hemisphere cortical volume contralateral to MAS, and, conversely, AI of MRI was significantly higher in CBS. PD patients exhibited an asymmetric pattern of brainstem excitability, compared to CBS. Conversely, CBS patients showed an asymmetric pattern of cortical atrophy. This opposite pattern of neurophysiological and structural abnormalities involving cortical and subcortical brain structures could highlight the different pathophysiological mechanisms underlying these disorders.

Morphometric magnetic resonance imaging cortico-subcortical features in Parkinson's disease with mild cognitive impairment.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients with cognitive impairment undergo progressive atrophy of several cortical and subcortical areas. The aim was to study the magnetic resonance imaging (MRI) morphometric features of PD patients with mild cognitive impairment (MCI). METHODS: Patients from the Parkinson's Disease Cognitive Impairment Study (PACOS) cohort with an available structural volumetric brain MRI and morphometric measurements of the midbrain and pons areas, middle cerebellar peduncle, superior cerebellar peduncle width and midbrain anteroposterior diameter (A-Pdiam) were included. MCI was diagnosed according to the Movement Disorder Society level II criteria. Additionally, cortical thickness analysis was performed and correlated with morphometric brainstem measurements. RESULTS: Morphometric measurements were available for 168 subjects, of whom 67 (39.9%) were diagnosed with PD-MCI. The mean age (± standard deviation) of the sample was 64.2 ± 9.8. Amongst patients, 84 (50%) were men with a disease duration of 5.2 ± 5.4 years and a Unified Parkinson's Disease Rating Scale-Motor Examination score of 32.1 ± 12.9. In the univariate and multivariate analysis, after adjusting for age, sex, years of schooling and disease duration, MCI was associated with midbrain area (odds ratio 0.98; 95% confidence interval 0.96-0.99; p = 0.048) and A-Pdiam (odds ratio 0.63; 95% confidence interval 0.46-0.86; p = 0.005). Furthermore, 121 PD patients underwent cortical thickness analysis, which showed the presence of cortical thinning in lateral orbitofrontal regions of patients with PD-MCI. No correlation was found between cortical thickness and brainstem morphometric measurements. CONCLUSIONS: A mild midbrain atrophy and the presence of frontal cortical thickness reduction might be considered a structural MRI feature of PD patients with MCI.

Obsessive-compulsive personality disorder in rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) is a common prodromic non-motor symptom of Parkinson's disease (PD). Only few studies have evaluated the personality of RBD patients with conflicting results. Aim of the study was to evaluate the frequency of Personality Disorders (PeDs)in RBD. RBD patients, PD patients and healthy controls (HC) were enrolled. All the enrolled subjects underwent a full neurological examination. Motor symptoms were evaluated with the UPDRS-Motor Examination. PeDs were assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). Twenty-nine RBD patients [14 men (48.3%); mean age 55.6 ± 11.1], 30 PD patients [17 men (56.7%); mean age 65.7 ± 10.7] and 30 HC [12 men (40%); mean age 65.7 ± 5.4] were enrolled in the study. PD patients had a disease duration of 4.5 ± 4.6 and presented a mean UPDRS-ME score of 26.7 ± 9.4. The most frequent PeDs was the Obsessive-Compulsive one (OCPeD); OCPeD was significantly more frequent in RBD (55.2%) patients than HC (13.3%; p-value < 0.001). No significant differences were found comparing the frequency of OCPeD in RBD patients to that in PD. In the present study, the prevalence of OCPeD in RBD patients was close to that reported in PD patients. Our data could suggest the existence of a common disease-specific RBD-PD personality profile.

Executive functioning and serum lipid fractions in Parkinson's disease-a possible sex-effect: the PACOS study.

The association between dyslipidemia and cognitive performance in Parkinson's disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29-9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = - 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17-0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18-0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.

Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients.

OBJECTIVE: To study the longitudinal disease course of Parkinson's disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. METHODS: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. RESULTS: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. CONCLUSIONS: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.

Influence of Drugs on Mild Cognitive Impairment in Parkinson's Disease: Evidence from the PACOS Study.

BACKGROUND: polytherapy and the anticholinergic activity of several drugs negatively influence cognition in the elderly. However, little is known on the effect on Mild Cognitive Impairment (MCI) in Parkinson's Disease (PD). METHODS: patients with PD belonging to the baseline PACOS cohort with full pharmacological data have been included in this study. MCI diagnosis was made according to the MDS level II criteria. Polytherapy was defined as patients assuming ≥6 drugs. The anticholinergic burden has been calculated using the Anticholinergic Drug Scale (ADS). Molecules have been classified according to the ATC classification. Association with MCI has been assessed with a multivariate logistic regression analysis with MCI as the dependent variable. RESULTS: pharmacological data were available for 238 patients (mean age 64.7±9.7). One hundred (42.0%) were diagnosed with MCI. No association was found in the full multivariate model (correcting for age, sex, disease duration, education, UPDRS-ME, LEDD-DAs) with either polytherapy or the ADS. Concerning drug classes, anti-hypertensive medications were positively associated with PD-MCI (OR 2.02;95%CI 1.04-3.89; p=0.035) while gastroprotective agents were negatively associated (OR 0.51; 95%CI 0.27-0.99; p=0.047). CONCLUSION: the magnitude of polytherapy and anticholinergic drugs burden does not appear to modulate MCI risk in PD, probably due to cautious prescription patterns. The effect of antihypertensive and gastroprotective agents on PD-MCI risk, while needing further confirmations, could be relevant for clinical practice.

Structural MRI substrate of long-duration response to levodopa in Parkinson's disease: an exploratory study.

OBJECTIVE: The long-duration response (LDR) to L-dopa is a sustained benefit deriving from chronic administration of therapy to patients with Parkinson's disease (PD). Almost all patients with early PD may develop the LDR to L-dopa, even if some patients could not at given dosages of the drug. Aim of this exploratory study is to investigate whether a neuroanatomical substrate may underlie the development of the of LDR using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analysis. METHODS: Twenty-four drug-naïve PD patients were enrolled and underwent a baseline 3D T1-weighted structural brain MRI. Then, a treatment with 250/25 mg of L-dopa/carbidopa every 24 h was started and, after 2 weeks, LDR was evaluated by movement time recordings. RESULTS: After 2 weeks of continuative therapy, 15 patients (62.5%) showed a sustained LDR (LDR +), while nine patients (37.5%) did not develop a sustained LDR (LDR -). VBM analysis on MRI executed before treatment showed changes of gray matter in precentral and middle frontal gyri in patients subsequently developing a sustained LDR with respect to those patients who will not achieve LDR. CONCLUSIONS: Parkinsonian patients who will develop a LDR to L-dopa may present, before starting treatment, peculiar structural conditions in cortical areas involved in motor control. Our exploratory study suggests that some cortical structural changes may predispose individual patients for developing the LDR to L-dopa.

Phonemic Verbal Fluency and Midbrain Atrophy in Progressive Supranuclear Palsy.

BACKGROUND: The neuropsychological profile of progressive supranuclear palsy (PSP) patients is mainly characterized by executive dysfunction, but the relationship between the latter and midbrain atrophy is still unclear. OBJECTIVE: The aims of the study were to investigate which test evaluating executive functioning is more frequently impaired in PSP patients and to evaluate the relationship between midbrain-based MRI morphometric measures and executive dysfunction. METHODS: PSP patients who had undergone a neuropsychological battery assessing executive functioning with the Frontal Assessment Battery (FAB), the phonemic verbal fluency F-A-S, the Raven's Progressive Colored Matrix, and the Stroop word colors test (time and errors) were enrolled in the study. A group of Parkinson's disease (PD) patients matched by age, sex, education, and global cognitive status was selected. All the enrolled patients also underwent a volumetric T1-3D brain MRI. RESULTS: Thirty-five PSP patients and 35 PD patients were enrolled. Patients with PSP as compared to patients with PD showed a significant greater impairment in verbal fluency (16.0±7.9 and 23.4±8.7 words/180 s; p < 0.001) and a significant lower score at the FAB total score (11.5±3.8 and 13.7±3.4; p = 0.013). Midbrain area was significantly smaller in PSP patients than in PD patients (83.9±20.1 and 134.5±19.9 mm2; p < 0.001). In PSP patients, a significant positive correlation between verbal fluency and the midbrain area (r = 0.421; p = 0.028) was observed. CONCLUSION: Our findings suggest that the phonemic verbal fluency is among the most frequently impaired executive functions in PSP patients and is strongly correlated to midbrain atrophy.

Neuroanatomical changes in early Parkinson's disease with mild cognitive impairment: a VBM study; the Parkinson's Disease Cognitive Impairment Study (PaCoS).

INTRODUCTION: Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), but the underlying pathological mechanism has not been fully understood. Voxel-based morphometry could be used to evaluate regional atrophy and its relationship with cognitive performances in early PD-MCI. PATIENTS AND METHODS: One hundred and six patients with PD were recruited from a larger cohort of patients, the Parkinson's Disease Cognitive Impairment Study (PaCoS). Subject underwent a T1-3D MRI and a complete clinical and neuropsychological evaluation. Patients were divided into PD with normal cognition (PD-NC) and PD-MCI according to the MDS level II criteria-modified for PD-MCI. A subgroup of early patients with short disease duration (≤ 2 years) was also identified. VBM analysis between PD-NC and PD-MCI and between early PD-NC and PD-MCI was performed using two-sample t tests with whole-brain statistical threshold of p < 0.001 uncorrected in the entire PD group and p < 0.05 FWE inside ROIs, in the early PD. RESULTS: Forty patients were diagnosed with MCI and 66 were PD-NC. PD-MCI patients showed significant gray matter (GM) reduction in several brain regions, including frontal gyrus, precuneus, angular gyrus, temporal lobe, and cerebellum. Early PD-MCI showed reduction in GM density in superior frontal gyrus and cerebellum. Moreover, correlation analysis between neuropsychological performances and GM volume of early PD-MCI patients showed associations between performances of Raven and superior frontal gyrus volume, Stroop time and inferior frontal gyrus volume, accuracy of Barrage and volume of precuneus. CONCLUSION: The detection of frontal and cerebellar atrophy, even at an early stage, could be used as an early marker of PD-related cognitive impairment.