Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.

Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.

OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D). DESIGN, SETTING AND PARTICIPANTS: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively. RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57). CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.

Development of the Digital Inclusion Questionnaire (DIQUEST) in Parkinson's Disease.

BACKGROUND: No tool is currently able to measure digital inclusion in clinical populations suitable for telemedicine. We developed the "Digital Inclusion Questionnaire" (DIQUEST) to estimate access and skills in Parkinson's Disease (PD) patients and verified its properties with a pilot study. METHODS: Thirty PD patients completed the initial version of the DIQUEST along with the Mobile Device Proficiency Questionnaire (MDPQ) and a practical computer task. A Principal Components Analysis (PCA) was conducted to define the DIQUEST factor structure and remove less informative items. We used Cronbach's α to measure internal reliability and Spearman's correlation test to determine the convergent and predictive validity with the MDPQ and the practical task, respectively. RESULTS: The final version of the DIQUEST consisted of 20 items clustering in five components: "advanced skills," "navigation skills," "basic skills/knowledge," "physical access," and "economical access." All components showed high reliability (α > 0.75) as did the entire questionnaire (α = 0.94). Correlation analysis demonstrated high convergent (rho: 0.911; p<0.001) and predictive (rho: 0.807; p<0.001) validity. CONCLUSIONS: We have here presented the development of the DIQUEST as a screening tool to assess the level of digital inclusion, particularly addressing the access and skills domains. Future studies are needed for its validation beyond PD.

Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

INTRODUCTION: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). METHODS: We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. RESULTS: The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. CONCLUSIONS: Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.

Magnetic Resonance T1w/T2w Ratio in the Putamen and Cerebellum as a Marker of Cognitive Impairment in MSA: a Longitudinal Study.

The exact pathophysiology of cognitive impairment in multiple system atrophy (MSA) is unclear. In our longitudinal study, we aimed to analyze (I) the relationships between cognitive functions and some subcortical structures, such as putamen and cerebellum assessed by voxel-based morphometry (VBM) and T1-weighted/T2-weighted (T1w/T2w) ratio, and (II) the neuroimaging predictors of the progression of cognitive deficits. Twenty-six patients with MSA underwent a comprehensive neuropsychological battery, motor examination, and brain MRI at baseline (T0) and 1-year follow-up (T1). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T1, we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (ß = - 9.45, p = .02) and T1w/T2w value in the left putamen (ß = 230.64, p = .01) were significant predictors of global cognitive status at T0, explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (ß = 2188.70, p = .02) significantly predicted cognitive worsening at T1, explaining 64% of the variance. Our results suggest a role for the putamen and cerebellum in the cognitive changes of MSA, probably due to their connections with the cortex. The putaminal T1w/T2w ratio may deserve further studies as a marker of cognitive impairment in MSA.

Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.

Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.

Higher Health Service Costs Associated With Delayed Diagnosis of Functional Neurological Disorder.

OBJECTIVE: Functional neurological disorder (FND) is frequently encountered in clinical practice but commonly misdiagnosed, which might lead to higher direct costs for the health care system. The investigators analyzed the direct costs associated with the diagnosis of FND compared with costs associated with other neurological conditions and explored possible cost trends related to the clinical and demographic features of FND. METHODS: Consecutive patients attending a general neurology clinic were recruited and underwent a structured assessment aimed to collect information pertaining to their demographic and clinical characteristics, as well as data regarding their prior diagnostic processes (e.g., the number of consulted specialists, number and type of investigations, emergency department visits, etc.). The costs were hence calculated and compared between the study groups. RESULTS: A total of 155 consecutive patients were recruited; of these, 18.6% had FND, 55.84% had one or more other neurological disorder (OND), and 27.10% presented with comorbid FND and OND. The total prediagnostic costs (in euros [€]) were higher in the FND group compared with the OND group (median=€289, interquartile range [IQR] €385 vs. median=€98, IQR €216; Mann-Whitney U=879.5, p=0.04). There was a higher diagnostic delay in the FND group compared with the OND group (median=48 months, IQR 60 months vs. median=12 months, IQR 6 months; Mann-Whitney U=162.00, p<0.01). Diagnostic delay significantly correlated with the total costs in the entire study sample (Spearman's ρ=0.25, p=0.003) but more strongly in the FND group (Spearman's ρ=0.81, p<0.001). In the FND group, higher numbers of investigations and costs were associated with the presence of a physiological or psychological trigger and multiple symptoms. CONCLUSIONS: Delayed diagnosis of FND significantly affects health care system costs, and raising awareness about FND to improve the diagnostic process and outcomes is necessary.

Screening performances of an 8-item UPSIT Italian version in the diagnosis of Parkinson's disease.

Hyposmia is a common finding in Parkinson's disease (PD) and is usually tested through the University of Pennsylvania Smell Identification Test (UPSIT). The aim of our study is to provide a briefer version of the Italian-adapted UPSIT test, able to discriminate between PD patients and healthy subjects (HS). By means of several univariate and multivariate (machine-learning-based) statistical approaches, we selected 8 items by which we trained a partial-least-square discriminant analysis (PLS-DA) and a decision tree (DT) model: class predictions of both models performed better with the 8-item version when compared to the 40-item version. An area under the receiver operating characteristic (AUC-ROC) curve built with the selected 8 odors showed the best performance (sensitivity 86.8%, specificity 82%) in predicting the PD condition at a cut-off point of ≤ 6. These performances were higher than those previously calculated for the 40-item UPSIT test (sensitivity 82% and specificity 88.2 % with a cut-off point of ≤ 21). Qualitatively, our selection contains one odor (i.e., apple) which is Italian-specific, supporting the need for cultural adaptation of smell testing; on the other hand, some of the selected best discriminating odors are in common with existing brief smell test versions validated on PD patients of other cultures, supporting the view that disease-specific odor patterns may exist and deserve a further evaluation.

Identification of a Gait Pattern for Detecting Mild Cognitive Impairment in Parkinson's Disease.

The aim of this study was to determine a gait pattern, i.e., a subset of spatial and temporal parameters, through a supervised machine learning (ML) approach, which could be used to reliably distinguish Parkinson's Disease (PD) patients with and without mild cognitive impairment (MCI). Thus, 80 PD patients underwent gait analysis and spatial-temporal parameters were acquired in three different conditions (normal gait, motor dual task and cognitive dual task). Statistical analysis was performed to investigate the data and, then, five ML algorithms and the wrapper method were implemented: Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB), Support Vector Machine (SVM) and K-Nearest Neighbour (KNN). First, the algorithms for classifying PD patients with MCI were trained and validated on an internal dataset (sixty patients) and, then, the performance was tested by using an external dataset (twenty patients). Specificity, sensitivity, precision, accuracy and area under the receiver operating characteristic curve were calculated. SVM and RF showed the best performance and detected MCI with an accuracy of over 80.0%. The key features emerging from this study are stance phase, mean velocity, step length and cycle length; moreover, the major number of features selected by the wrapper belonged to the cognitive dual task, thus, supporting the close relationship between gait dysfunction and MCI in PD.

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.

BACKGROUND: The second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages. OBJECTIVE: To develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology. METHODS: We identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference. RESULTS: The criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow. CONCLUSIONS: This set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fist-Palm Test (FiPaT): a bedside motor tool to screen for global cognitive status.

OBJECTIVE: The Fist-Palm Test (FiPaT) is a novel non-verbal task to be used at the patient's bedside for a cognitive functions screening. The aims of this study are to analyze (I) the qualitative and quantitative performance features at FiPaT, (II) the psychometric characteristics of FiPaT, and (III) the correlation between FiPat and traditional cognitive assessments in subjects with normal cognition (NC), Mild Cognitive Impairment-single domain (MCI-sd), and Mild Cognitive Impairment-multiple domain (MCI-md). METHODS: One hundred-thirteen subjects (53M/60F), with a mean age of 66.28 ± 7.22 years and 11.08 ± 4.93 years of education, were recruited and underwent a complete neuropsychological battery and FiPaT. RESULTS: We found 68 subjects with NC, 31 with MCI-sd, and 14 with MCI-md and a high reliability of the FiPaT (alpha =0.762). The number of FiPaT errors correlated with age and all neuropsychological tests, except for the memory recall test. Subjects with MCI had greater FiPaT errors than subjects with NC. The FiPaT, used with the MOCA test, predicted the presence of MCI, with a variance of 44%. CONCLUSION: The FiPaT is an acceptable and reliable non-verbal test, able to screen for global cognitive status, attention, and executive functions, and to predict the MCI. Future studies will validate this initial findings as well as the discriminatory role of the FiPaT in detecting specific types of cognitive impairment.

Reliability and validity of the novel Italian version of the 14-item Resilience Scale (RS-14) in adults.

BACKGROUND: The aims of this explore the psychometric properties of the novel Italian version of the 14-item Resilience Scale (RS-14) and to assess the relationship between RS-14, mood and quality of life. METHOD: The original English version of the RS-14 was translated into Italian, and the Italian version was confirmed with back-translation. Three-hundred healthy volunteers (M = 122) aged > 18 years, completed the RS-14 as well as different scales to measure depression, anxiety and quality of life. Statistical analyses were used to measure the reliability, validity and key factors of RS-14. We measured the differences in socio-demographic subgroups, the relationship between mood and RS-14 score and the impact of RS-14 on mental health. RESULTS: The RS-14 showed good acceptability, reliability and validity. Factor analysis indicated a two-factor structure: 'Self-confidence' and 'Self-control', with the former having a more significant impact on mental health. The RS-14 score was not significantly different for sex, age and education, but there was significant difference for marital status. Lower resilience correlated with higher levels of anxiety and depression and with lower quality of life. CONCLUSION: We propose the novel Italian version of the RS-14 which has good reliability and validity. Our results stress the influence of resilience on mental health.

Uncovering clinical and radiological asymmetry in progressive supranuclear palsy-Richardson's syndrome.

BACKGROUND: Richardson's syndrome (RS) is considered the most symmetric phenotype of progressive supranuclear palsy (PSP) as opposed to PSP with predominant corticobasal syndrome (PSP-CBS) or parkinsonism (PSP-P). OBJECTIVES: Evaluate asymmetrical motor and higher cortical features in probable PSP-RS and compare the degree of asymmetry of cortical lobes and hemispheres between PSP-RS, PSP-CBS, PSP-P, and age-matched healthy controls (HC). METHODS: Asymmetry of motor and higher cortical features evaluated with an extensive videotaped neurologic examination was investigated in 28 PSP-RS, 8 PSP-CBS, and 14 PSP-P. Brain MRI to compute the laterality index (LI) was performed in 36 patients as well as in 56 HC. RESULTS: In PSP-RS, parkinsonism was the most common asymmetric motor feature (53.6%), followed by dystonia and myoclonus (21.4% and 17.9%, respectively). Among higher cortical features, limb apraxia was found asymmetric in about one-third of patients. PSP-RS disclosed higher LI for hemispheres compared to HC, indicating a greater degree of asymmetry (p = 0.003). The degree of asymmetry of clinical features was not different between PSP-RS and those qualifying for PSP-CBS or PSP-P. As for imaging, LI was not different between PSP-RS, PSP-CBS, and PSP-P in any cortical region. CONCLUSIONS: Motor and higher cortical features are asymmetric in up to 50% of PSP-RS who also present a greater degree of asymmetry in hemispheres compared to age-matched HC. Lateralization of clinical features should be annotated in PSP.

Retinal thinning in progressive supranuclear palsy: differences with healthy controls and correlation with clinical variables.

BACKGROUND: Available evidence reports conflicting data on retinal thickness in progressive supranuclear palsy (PSP). In studies including healthy controls, PSP showed either the thinning of the retinal nerve fiber layer, macular ganglion cell, inner nuclear, or outer retina layer. OBJECTIVES: The goals of the present study were to describe retinal layer thickness in a large cohort of PSP compared to healthy controls and in PSP phenotypes using spectral-domain optical coherence tomography (SD-OCT). The additional objective was to verify the relationship between retinal layers thickness and clinical variables in PSP. METHODS: Using a cross-sectional design, we examined retinal structure in 27 PSP patients and 27 controls using standard SD-OCT. Motor and cognitive impairment in PSP was rated with the PSP rating scale and the Montreal Cognitive Assessment battery (MoCA), respectively. Eyes with poor image quality or confounding diseases were excluded. SD-OCT measures of PSP and controls were compared with parametric testing, and correlations between retinal layer thicknesses and disease severity were evaluated. RESULTS: PSP showed significant thinning of the inner retinal layer (IRL), ganglion cell layer (GCL), inner plexiform layer (IPL), and the outer plexiform layer (OPL) compared to healthy controls. PSP phenotypes showed similar retinal layer thicknesses. Retinal layer thickness correlated with MoCA visuospatial subscore (p < 0.001). CONCLUSIONS: We demonstrated PSP patients disclosed thinner IRL, GCL, IPL, and OPL compared to healthy controls. Furthermore, we found a significant correlation between visuospatial abilities and retinal layers suggesting the existence of a mutual relationship between posterior cognitive function and retinal structure.

The Role of VPS35 in the Pathobiology of Parkinson's Disease.

The vacuolar protein sorting 35 (VPS35) gene located on chromosome 16 has recently emerged as a cause of late-onset familial Parkinson's disease (PD) (PARK17). The gene encodes a 796-residue protein nearly ubiquitously expressed in human tissues. The protein localizes on endosomes where it assembles with other peripheral membrane proteins to form the retromer complex. How VPS35 mutations induce dopaminergic neuron degeneration in humans is still unclear. Because the retromer complex recycles the receptors that mediate the transport of hydrolase to lysosome, it has been suggested that VPS35 mutations lead to impaired lysosomal and autophagy function. Recent studies also demonstrated that VPS35 and the retromer complex influence mitochondrial homeostasis, suggesting that VPS35 mutations elicit mitochondrial dysfunction. More recent studies have identified a key role of VPS35 in neurotransmission, whilst others reported a functional interaction between VPS35 and other genes associated with familial PD, including α-SYNUCLEIN-PARKIN-LRRK2. Here, we review the biological role of VPS35 protein, the VPS35 mutations identified in human PD patients, and the potential molecular mechanism by which VPS35 mutations can induce progressive neurodegeneration in PD.

The language profile in multiple system atrophy: an exploratory study.

BACKGROUND: The evidence about the language performance profile of multiple system atrophy (MSA) is limited, but its definition may lead to a more comprehensive characterization of the disorder and contribute to clarify the involvement of the basal ganglia in language abilities. OBJECTIVE: The objectives of the study were: (1) to evaluate the reliability of the Screening for Aphasia in NeuroDegeneration (SAND) in MSA patients; (2) compare the linguistic profiles among MSA and Parkinson's disease (PD) patients and healthy controls (HC), and (3) assess relationships between language impairment and cognitive status and MSA motor subtypes. METHODS AND RESULTS: Forty patients with a diagnosis of MSA, 22 HC and 17 patients with PD were enrolled in the present study. By excluding the writing task that showed a poor acceptability, we showed that the MSA-tailored SAND Global Score is an acceptable, consistent and reliable tool to screen language disturbances in MSA. MSA patients performed worse than HC, but not than PD, in MSA-tailored SAND Global Score, repetition, reading and semantic association tasks. We did not find significant differences between MSA phenotypes. MSA patients with mild cognitive impairment-multiple domain presented worse language performances as compared to MSA patients with normal cognition and mild cognitive impairment-single domain. CONCLUSION: The MSA-tailored SAND Global Score is a consistent and reliable tool to screen language disturbances in MSA. Language disturbances characterize MSA patients irrespective of disease phenotype, and parallel the decline of global cognitive functions.

Limitations of the Unified Multiple System Atrophy Rating Scale as outcome measure for clinical trials and a roadmap for improvement.

PURPOSE: The unified multiple system atrophy (MSA) rating scale (UMSARS) was developed almost 20 years ago as a clinical rating scale to capture multiple aspects of the disease. With its widespread use, the shortcomings of the UMSARS as a clinical outcome assessment (COA) have become increasingly apparent. We here summarize the shortcomings of the scale, confirm some of its limitations with data from the Natural History Study of the Synucleinopathies (NHSS), and suggest a framework to develop and validate an improved COA to be used in future clinical trials of disease-modifying drugs in patients with MSA. METHODS: Expert consensus assessment of the limitations of the UMSARS and recommendations for the development and validation of a novel COA for MSA. We used UMSARS data from the ongoing NHSS (ClinicalTrials.gov: NCT01799915) to showcase some of these limitations. RESULTS: The UMSARS in general, and specific items in particular, have limitations to detect change resulting in a ceiling effect. Some items have specific limitations including unclear anchoring descriptions, lack of correlation with disease severity, susceptibility to improve with symptomatic therapies (e.g., orthostatic hypotension, constipation, and bladder dysfunction), and redundancy, among others. CONCLUSIONS: Because of the limitations of the UMSARS, developing and validating an improved COA is a priority. The time is right for academic MSA clinicians together with industry, professional societies, and patient advocacy groups to develop and validate a new COA.

Vitamin D as a possible biomarker of mild cognitive impairment in parkinsonians.

INTRODUCTION: Mild Cognitive Impairment in Parkinson's Disease (PD-MCI) is a transitional state between normal cognition and dementia. Cross-sectional studies revealed that low Vitamin D levels were associated with worse performance on cognitive tests in Parkinson's Disease. The present longitudinal study aimed to examine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at baseline and possible development of PD-MCI at 24 and 48 months. MATERIALS AND METHODS: Sixty untreated, de novo PD patients underwent clinical and cognitive evaluations and measurement of serum 25(OH)D at baseline assessment (T0). After 24 (T1) and 48 months (T2), cognitive status (presence or absence of PD-MCI) of PD patients were re-evaluated. RESULTS: Vitamin D insufficiency occurred in 93.3% at T0. At T1, significant differences among patients with PD-MCI at both baseline and follow-up, patients with PD-MCI at follow-up and patients who never developed PD-MCI were found on age, age at onset of PD, and education; no significant difference was found on vitamin D levels at T0. A binary logistic regression analysis showed that a lower level of 25(OH)D at T0 (B= -0.158, Wald= 5.280, p = 0.022, Exp (B)=0.854; CI 95%: 0.746-0.977) and lower education (B= -0.214, Wald= 3.859, p = 0.049, Exp (B)=0.807; CI 95%: 0652-1.000) were predictors of PD-MCI occurrence at T2. DISCUSSION: Our results demonstrated that a lower level of 25(OH)D is conceivable as a biomarker of development of PD-MCI throughout the disease. Early diagnosis of Vitamin D insufficiency and its management might be useful to prevent cognitive decline in PD patients.

Midbrain MRI assessments in progressive supranuclear palsy subtypes.

OBJECTIVES: To explore the role of the available midbrain-based MRI morphometric assessments in (1) differentiating among progressive supranuclear palsy (PSP) subtypes (PSP Richardson's syndrome (PSP-RS), PSP with predominant parkinsonism (PSP-P) and the other variant syndromes of PSP (vPSP)), and (2) supporting the diagnosis of PSP subtypes compared with Parkinson's disease (PD) and healthy controls (HC). METHODS: Seventy-eight patients with PSP (38 PSP-RS, 21 PSP-P and 19 vPSP), 35 PD and 38 HC were included in the present analysis. Available midbrain-based MRI morphometric assessments were calculated for all participants. RESULTS: Current MRI midbrain-based assessments do not display an adequate sensitivity and specificity profile in differentiating PSP subtypes. On the other hand, we confirmed MR Parkinsonism Index (MRPI) and pons area to midbrain area ratio (P/M) have adequate diagnostic value to support PSP-RS clinical diagnosis compared with both PD and HC, but low sensitivity and specificity profile in differentiating PSP-P from PD as well as from HC. The same measures show acceptable sensitivity and specificity profile in supporting clinical diagnosis of vPSP versus HC but not versus PD. Similar findings were detected for the newer MRPI and P/M versions. CONCLUSIONS: Further studies are warranted to identify neuroimaging biomarkers supporting the clinical phenotypic categorisation of patients with PSP. MRPI and P/M have diagnostic value in supporting the clinical diagnosis of PSP-RS. CLASSIFICATION OF EVIDENCE: This study provides class III evidence that available MRI midbrain-based assessments do not have diagnostic value in differentiating the Movement Disorder Society PSP subtypes.

GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort.

BACKGROUND: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. ß-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest ß-glucocerebrosidase activity. CONCLUSIONS: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.