Abstract INTRODUCTION Clinical effects and prevalence of Lewy body (LB) pathology in patients with mild cognitive impairment (MCI) remain poorly understood. METHODS We assessed LB pathology in 339 patients with MCI from the Italian multicenter Interceptor cohort using the cerebrospinal fluid α‐synuclein seed amplification assay. Baseline assessment was followed by serial cognitive evaluations over 3 years. RESULTS LB+ participants (n = 50, 15%) were older and showed a higher frequency of parkinsonism, falls, and delirium episodes than those LB–, although these differences were not statistically significant. At follow‐up, patients with biomarker evidence of Alzheimer's disease (AD), either isolated (AD+/LB–) or with concomitant LB pathology (AD+/LB+), showed the fastest cognitive decline and progression to dementia. DISCUSSION In a multicenter MCI cohort, LB pathology was associated with older age and an increased frequency of motor/psychiatric symptoms. Larger studies are needed to clarify the independent contribution of AD and LB pathologies to the MCI phenotype and clinical progression.

BACKGROUND:Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals at high risk of progression is crucial for public health strategies. METHODS:The INTERCEPTOR project included 398 MCI individuals. Baseline assessment included harmonized procedures for sociodemographic, clinical, neuropsychological, genetic (apolipoprotein E), cerebrospinal fluid (amyloid beta tau), electroencephalogram (brain connectivity), magnetic resonance imaging (hippocampal volumetry), and fluorodeoxyglucose positron emission tomography. The baseline and follow-up were completed by 351 individuals with MCI with neuropsychological tests every 6 months for 3 years. RESULTS:Dementia developed in 104 individuals (29.6%), including 85 (22.4%) who met core clinical criteria for probable and possible Alzheimer's disease dementia. A Cox model combining clinical and sociodemographic data achieved a concordance index of 72%, which increased to 82% when neuropsychology and biomarkers were added. DISCUSSION:The INTERCEPTOR nomogram represents a tool for predicting dementia progression risk, supporting public health strategies, including screening for risk assessment and risk/benefit ratio in innovative treatments.

Timely and accurate diagnosis of Alzheimer’s disease (AD) in clinical practice is a great challenge, especially during early disease stages with subtle or mild symptoms of cognitive decline. Moreover, robust and more accessible blood-based screening tests for early diagnosis are needed. In this study, we investigated the core AD blood biomarkers — amyloid beta 42 (Aβ42) and 40 (Aβ40) peptides, phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), and total tau (t-Tau) — and extracellular vesicle (EVs) size and concentration in individuals characterized by different stages of cognitive decline to identify biochemical markers of dementia for early diagnosis. A total of n = 800 human plasma samples were analyzed. Plasma levels of NfL, t-Tau, p-Tau181, Aβ42, Aβ40 and plasma EVs were evaluated in n = 217 elderly healthy subjects (CTRL), in individuals with subjective cognitive complaints (SCC, n = 48), pre-mild cognitive impairment (pre-MCI, n = 58) and mild cognitive impairment (MCI, n = 426), and in n = 51 probable AD dementia patients (AD-dem), using ultrasensitive Single Molecule Array technology (Simoa®) and nanoparticle tracking analysis (NTA). Logistic regression and Receiver Operating Characteristic (ROC) analyses were employed. Plasma NfL displayed increased levels in AD-dem and MCI patients, while p-Tau181, Aβ42/Aβ40 ratio, Aβ42/p-Tau181 ratio, and EVs plasma levels were altered since the early stages of the pathology: in particular, p-Tau181 levels increased as cognitive symptoms worsened, already in the SCC and pre-MCI groups compared to CTRL, while the ratio of EVs concentration and size (EVs ratio) was decreased in all groups compared to CTRL. Plasma p-Tau181 best classified AD-dem patients from CTRL with an area under the curve (AUC) equal to 0.87, while EVs ratio best differentiated SCC from CTRL (AUC = 0.78). Combining p-Tau181 and EVs ratio with Aβ42/Aβ40 ratio and NfL, respectively, significantly improved the classification of pre-MCI and MCI from CTRL (AUCcomb = 0.79 and AUCcomb = 0.85). Combining biomarkers did not improve accuracy in discriminating MCI from SCC, pre-MCI and AD-dem. p-Tau181 and EVs ratio are promising biomarkers for the identification of individuals at risk of degenerative dementia. Combining the core AD plasma biomarkers with EVs ratio can aid in diagnosing the early stages of AD dementia.

Frontotemporal dementia (FTD) is a heterogeneous disorder for which disease-modifying treatments are lacking. Non-invasive brain stimulation (NIBS) has emerged as a potential therapeutic approach to modulate dysfunctional neural networks and support residual plasticity. This systematic review aims to provide an updated overview of current NIBS applications across the main clinical syndromes associated with FTD, namely behavioral variant FTD (bvFTD), semantic variant of primary progressive aphasia (svPPA), and nonfluent variant of PPA (nfvPPA). According to PRISMA guidelines, twenty-seven studies investigating NIBS interventions in major FTD phenotypes met the inclusion criteria, predominantly employing transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS). tDCS, particularly when combined with language therapy, consistently improved several language abilities in PPA, with some evidence of maintenance over time. Benefits were most consistently reported in nfvPPA, whereas effects in svPPA were more limited and domain-specific. rTMS studies showed short-term improvements in language and executive functions, especially following stimulation of left frontal regions. In bvFTD, findings were heterogeneous, with social-cognitive outcomes appearing more sensitive to stimulation, whereas global cognitive measures showed more variable effects. NIBS, particularly tDCS combined with behavioral interventions, shows symptomatic potential in selected FTD phenotypes, but methodological heterogeneity and small samples warrant larger, well-controlled trials.

Background: In recent years, there has been increasing interest in the application of repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct-Current Stimulation (tDCS) to enhance and rehabilitate the language abilities in individuals with neurodegenerative diseases. Objective: The aim of this narrative literature review is to investigate the usefulness of rTMS and tDCS to improve language abilities in people with Primary Progressive Aphasia (PPA). Methods: This narrative literature review was conducted through a search of the PubMed online database to identify studies investigating the effects of multiple sessions of rTMS or tDCS on language abilities in PPA patients, applied either as stand-alone interventions or in combination with language treatment. Results: Thirty-three studies fulfilled the inclusion criteria; five studies employed rTMS without language treatment; two studies applied tDCS as stand-alone intervention; twenty-two studies combined tDCS with language treatment; and four studies assessed the effects of tDCS during verbal task without language treatment. Conclusions: rTMS and tDCS applied with or without concomitant language treatment appear to be promising interventions for enhancing language abilities in PPA, with sustained effects reported over time. Further research is necessary to optimise stimulation protocols and to improve our understanding of their long-term effects. Moreover, randomised controlled trials (RCTs) with larger sample sizes are critically needed to clarify the true impact of brain stimulation in PPA, with a focus on changes in cognitive and functional performance, neural activity, and potential molecular correlates.

The non-fluent/agrammatic variant of primary progressive aphasia is a neurodegenerative disorder characterized by effortful language production and impaired comprehension of grammatically complex sentences. Recently, interest in non-pharmacological interventions has increased, particularly regarding techniques that allow for non-invasive brain stimulation, such as transcranial direct current stimulation. The main purpose of this study was to investigate whether the use of anodal transcranial direct current stimulation applied to the dorsolateral prefrontal cortex during individualized language training for 25 min a day at 5 days a week for 2 weeks would lead to significant oral naming improvements in patients with agrammatic variant of primary progressive aphasia. Specifically, we hypothesized that anodal transcranial direct current stimulation plus individualized language training may improve the oral naming of treated and untreated objects compared with both placebo transcranial direct current stimulation plus individualized language therapy and anodal transcranial direct current stimulation combined with computerized cognitive training. Forty-seven agrammatic variant of primary progressive aphasia patients were consecutively enrolled and randomized into one of three groups that received the following treatments: (i) anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex during individualized language rehabilitation treatment; (ii) placebo transcranial direct current stimulation during individualized language rehabilitation treatment; or (iii) anodal transcranial direct current stimulation with computerized cognitive training. Clinical, neuropsychological and language assessments were recorded at baseline (T0), post-treatment (T1, 2 weeks) and at 12 weeks from T0 (T2). Magnetic resonance imaging data, functional magnetic resonance imaging data and blood samples were collected at T0 and T1. All of the groups demonstrated improvements in oral object naming at T1, with maintenance effects being observed at T2. At T1, the enhancement in the oral naming of treated and untreated objects was significantly greater in patients who underwent anodal transcranial direct current stimulation during individualized language rehabilitation treatment. There were no significant changes observed across the groups regarding the magnetic resonance imaging, functional magnetic resonance imaging or blood biochemical marker data. Our results support the beneficial effects of individualized language rehabilitation treatment in combination with anodal transcranial direct current stimulation in agrammatic variant of primary progressive aphasia patients.

BackgroundMild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD) are heterogeneous conditions that may indicate early dementia. Virtual Reality (VR) is emerging as a promising non-pharmacological tool for cognitive training. However, its effectiveness in these populations remains unclear. This systematic review examines the impact of VR-based cognitive interventions in individuals with SCD and MCI.MethodsA systematic review was conducted in accordance with PRISMA guidelines. Studies published between 2019 and 2025 investigating VR-based cognitive interventions in individuals diagnosed with SCD or MCI were identified through searches in PubMed, Scopus, Embase, and Web of Science. Eligible studies included randomized controlled trials (RCTs), experimental studies, and usability studies.ResultsNineteen studies met the inclusion criteria, including 14 RCTs, 2 usability studies, and 3 experimental studies. The majority of studies reported significant improvements in various cognitive domains, particularly memory, attention, and executive function, following VR-based interventions. Several studies also highlighted the positive impact of VR on user engagement and motivation, with high adherence and low dropout rates. However, there was considerable variability in intervention protocols, cognitive outcome measures, and participant characteristics. Most studies focused on individuals with MCI, while research on SCD populations remains limited and preliminary. Methodological quality varied, with some studies lacking adequate sample sizes or long-term follow-up.ConclusionVR-based cognitive interventions appear to be a feasible and potentially effective approach for enhancing cognitive function in individuals with MCI, with emerging evidence also supporting their use in SCD. Despite encouraging results, further high-quality, large-scale trials are needed to validate these findings, standardize intervention protocols, and explore long-term benefits.Systematic review registrationCRD42025644894.

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. Methods: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. Results: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians’ diagnostic confidence when TMS data were incorporated. Conclusions: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability.

BACKGROUND:The Italian Interceptor project is aimed at identifying a prodromal dementia phase and developing a nationwide organizational model. This study compares the sociodemographic and neuropsychological characteristics of mild cognitive impairment non-converters (MCI-NC) and MCI-converters (MCI-C) to dementia, including Alzheimer's disease (AD), enrolled during the Interceptor project. METHODS:Sociodemographic, clinical, and neuropsychological data of MCI individuals were collected at baseline (December 2018 to October 2020) and every six-month follow-up visit for 3 years. Logistic regression and Random Forest classifier were used to describe the study population. RESULTS:From 356 participants, 104 were MCI-C, whereas 252 were MCI-NC. Compared to MCI-NC, MCI-C were predominantly female (p = 0.020), older (p < 0.001), and more cognitively impaired (p < 0.001). Higher physical activity was protective for progression (p < 0.001), but no difference was observed for smoking exposure (p = 0.312) between the two groups. Similar results were found for AD individuals compared to MCI-C/non-AD. The ROC curve based on a Random Forest classifier distinguishing MCI-C from MCI-NC showed an area under the curve (AUC) of 0.7347. CONCLUSIONS:Our findings confirm previous evidence in literature and may increase the insight on dementia pathology and help in defining intervention strategies to prevent or slow down disease progression.

Background: Healthy cognitive functioning is a primary component of well-being, independence, and successful aging. Cognitive deficits can arise from various conditions, such as brain injury, mental illness, and neurological disorders. Rehabilitation is a highly specialized service limited to patients who have access to institutional settings. In response to this unmet need, telehealth solutions are ideal for triggering the migration of care from clinics to patients’ homes. Objectives: The aim of EARLY-COGN^3 will be threefold: (1) to test the efficacy of a digital health at-home intervention (tele@cognitive protocol) as compared to an unstructured cognitive at-home rehabilitation in a cohort of patients with Chronic Neurological Diseases (CNDs); (2) to investigate its effects on the biomolecular and neurophysiological marker hypothesizing that people with CNDs enrolled in this telerehabilitation program will develop changes in biological markers and cortical and subcortical patterns of connectivity; (3) to analyze potential cognitive, neurobiological, and neurophysiological predictors of response to the tele@cognitive treatment. Method: In this single-blind, randomized, and controlled pilot study, we will assess the short- and long-term efficacy of cognitive telerehabilitation protocol (tele@cognitive) as compared to an unstructured cognitive at-home rehabilitation (Active Control Group—ACG) in a cohort of 60 people with Mild Cognitive Impairment (MCI), Subjective Cognitive Complaints (SCCs), or Parkinson’s Disease (PD). All participants will undergo a clinical, functional, neurocognitive, and quality of life assessment at the baseline (T0), post-treatment (5 weeks, T1), and at the 3-month (T2) follow-up. Neurophysiological markers and biomolecular data will be collected at T0 and T1. Conclusions: EARLY-COGN^3 project could lead to a complete paradigm shift from the traditional therapeutic approach, forcing a reassessment on how CNDs could take advantage of a digital solution. (clinicaltrials.gov database, ID: NCT06657274)

INTRODUCTION:Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis. METHODS:This cohort study included 374 participants (96 AD, 278 FTLD). Plasma phosphorylated tau (p-tau)217, neurofilament light chain (NfL), brain-derived tau, glial fibrillary acidic protein, and the amyloid beta1-42/1-40 ratio were measured. Receiver operating characteristic curve analyses assessed diagnostic accuracy, and a three-range threshold approach was used to stratify patients based on the most accurate biomarker. RESULTS:Plasma p-tau217 effectively distinguished AD from FTLD, with the NfL/p-tau217 ratio showing superior accuracy. The three-range approach identified thresholds with 95% and 97.5% sensitivity and specificity, reducing the need for cerebrospinal fluid testing by 75% and 54%, respectively. DISCUSSION:Plasma p-tau217 and the NfL/p-tau217 ratio are promising non-invasive biomarkers for differentiating AD from FTLD, suggesting their use as a potential alternative to traditional diagnostic methods. HIGHLIGHTS:Plasma phosphorylated tau (p-tau)217 distinguishes Alzheimer's disease (AD) from frontotemporal lobar degeneration (FTLD) with high accuracy. The neurofilament light chain/p-tau217 ratio showed the highest accuracy for differentiating AD from FTLD. A three-range threshold reduces the need for invasive cerebrospinal fluid testing or amyloid positron emission tomography imaging.

INTRODUCTION:Modeling the survival rate in syndromes associated with frontotemporal lobar degeneration (FTLD) is essential to assess disease trajectories. METHODS:In 262 patients with FTLD, we considered plasma neurofilament light chain (NfL), glial fibrillary acidic protein, brain-derived tau, phosphorylated tau217 and amyloid beta (Aβ42/Aβ40). The FTLD Survival Score (FTLD-SS) was calculated by the β coefficients of the variables independently associated with survival rate. RESULTS:Increased plasma NfL levels (p < 0.001), older age at evaluation (p = 0.002), positive family history (p = 0.04), and motor phenotypes (p < 0.001) were associated with reduced survival. The predictive validity of FTLD-SS was 0.75 (95% confidence interval, 0.59-0.91) at 1 year. DISCUSSION:Survival rate in FTLD is shaped by intensity of neurodegeneration (using plasma NfL as proxy) together with certain clinical variables. The FTLD-SS may serve as a simple tool for survival rate estimation and for patient stratification in clinical trials. HIGHLIGHTS:Plasma neurofilament light chain and clinical variables can predict survival in frontotemporal lobar degeneration (FTLD)-associated syndromes. FTLD Survival Score (FTLD-SS), computed with survival predictors, may serve as a simple tool for patient stratification. FTLD-SS is associated with greater atrophy in frontal and putamen areas.

INTRODUCTION:Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia, with 30%-50% of cases progressing to dementia. However, some individuals remain stable over time, even when presenting biomarker profiles that indicate high risk. Understanding the neural mechanisms underlying this resilience is essential for developing targeted preventive strategies. METHODS:Within the Italian INTERCEPTOR project, we investigated electroencephalography (EEG) markers of resilience in MCI individuals who exhibited reduced hippocampal volume and abnormal fluorodeoxyglucose-positron emission tomography (FDG-PET) at baseline but remained stable and did not progress to dementia after 36 months. Two MCI subgroups were compared: those who do not convert (sMCI-resilient) and those who converted (cMCI) to dementia. A third group of cognitively healthy, age- and education-matched older adults served as controls. Baseline EEG analyses examined spectral power, delta/alpha ratio, functional connectivity, and graph-theoretical network properties. RESULTS:Compared with sMCI-resilient subjects, cMCI individuals exhibited increased frontal delta power, reduced posterior alpha power, and an elevated delta/alpha ratio in the right temporal region, consistent with cortical dysfunction. In contrast, sMCI-resilient subjects showed stronger frontal and temporal alpha-band connectivity and higher small-world (SW) index values in the alpha-2 band, suggesting more efficient network organization. DISCUSSION:Specific EEG signatures-characterized by adaptive spectral patterns, preserved connectivity, and efficient network topology-may represent neurophysiological correlates of resilience in high-risk MCI. These findings highlight the potential of EEG markers for early intervention and stratification strategies in individuals at risk of dementia. Highlights:Electroencephalography (EEG) markers differentiate resilience and progression in mild cognitive impairment (MCI) individuals with high-risk biomarker profiles.Converters (cMCI) show increased delta power, reduced alpha activity, and higher delta/alpha ratios, indicating cortical dysfunction.Resilient MCI (sMCI) maintain healthy delta profiles, enhanced frontal alpha power, and stronger anterior connectivity.Graph-theoretical analysis reveals higher small-world (SW) index in resilient MCI, suggesting efficient and flexible network organization.EEG is a non-invasive, accessible tool to capture both risk and resilience factors, with potential for early diagnosis and personalized interventions.

Objective Rehabilitation is an important player in preventing and reducing the high impact of disability on everyday functioning in chronic neurological diseases (CNDs), especially if timely, intensive, and multidimensional. However, to date, rehabilitation is often a service accessible only to a few people, and the issue of a progressive decrease in treatment adherence still remains to be addressed. This study protocol describes an RCT whose aim is to test the effectiveness in terms of adherence of DANCE Rehabilitation EXperience (DANCEREX-DTx), a new digital therapeutic solution which combines a holistic, multidimensional program based on dance and music with an innovative motivational system. Methods The randomized, single-blind, controlled trial will involve 192 patients with CNDs from three rehabilitation centers in Italy. Participants will be randomized (with an allocation ratio of 2:2:1) into three interventions: (1) DANCEREX treatment, (2) multidimensional dance-based program, and (3) educational program. Groups will be assessed at the baseline (T0), after intervention (T1—after 12 weeks), and after six months from enrollment (T2). The primary outcome will be treatment adherence in terms of the number of drop-outs and the percentage of attended sessions on the total prescribed. Moreover, a multifaceted evaluation, including quality of life and clinical/functional measures, will be conducted at each time-point. Surrogate measures (neuroimaging and neurobiological) will be collected at T0 and T1. Finally, usability and acceptability will be assessed at T1. Results We expect the validation, in terms of usability, acceptability, and effectiveness of DANCEREX-DTx as an innovative rehabilitation program able to respond in a sustainable way to the great need for rehabilitation of people with CNDs. Conclusion With DANCEREX-DTx, we aspire to change the hospital-centered paradigm of rehabilitation care to bring it to the patients' homes, making them active in their treatment path and promoting motivation and adherence to treatment from the initial stages of the disease. Trial registration : The trial was registered in the clinicaltrials.gov database (identifier NCT06112639) on 2023-11-01.

The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer’s Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI). The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse® G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles. We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects. Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.

The availability of remotely administered neuropsychological batteries is crucial to provide access to care in extraordinary situations, e.g., the recent pandemic, and for individuals with reduced mobility. Here we present the normative data of the remotely administered version of the Italian Uniform Data Set Neuropsychological Battery (tele-I-UDSNB), developed by our group. I-UDSNB included Craft Story, Benson Figure, Digit Span, Semantic and Phonemic Fluency, Trail Making Test A and B, Picture Naming, and the Five Words Test, which were adapted to be administered via web-based communication software. The tele-I-UDSNB was administered to 157 healthy participants who also underwent the face-to-face version of the battery. Regression models were used to evaluate the impact of demographic variables on performance and to obtain reference norms. The effect of modality and order of administration was assessed by factorial ANOVAs. Age predicted the performances on most of the tests, whereas education was associated with performance on Craft Story, Benson Figure, Digit Span, Semantic and Phonemic Fluency, and Trail Making Test. Sex affected some subscores of Semantic Fluency and Digit Span. The modality of administration showed little influence on the performance, limited to scores related to Semantic Fluency. The tele-I-UDSNB could be a useful tool for tele-neuropsychological assessment, with the modality of administration only showing a limited effect on some sub-scores.

A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5-12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99-3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.

Abstract Background The identification and staging of Alzheimer’s Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. Methods One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. Results Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. Conclusions Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.