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IntroductionA new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic.MethodsA list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak.ResultsIn total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open.ConclusionThis paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia.

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches—namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide.

Corticobasal syndrome (CBS) is a clinical syndrome determined by various underlying neurodegenerative disorders requiring a pathological assessment for a definitive diagnosis. A literature review was performed following the methodology described in the Cochrane Handbook for Systematic Reviews to investigate the additional value of traditional and cutting-edge cerebrospinal fluid (CSF) and serum/plasma biomarkers in profiling CBS. Four databases were screened applying predefined inclusion criteria: (1) recruiting patients with CBS; (2) analyzing CSF/plasma biomarkers in CBS. The review highlights the potential role of the association of fluid biomarkers in diagnostic workup of CBS, since they may contribute to a more accurate diagnosis and patient selection for future disease-modifying agent; for example, future trial designs should consider baseline CSF Neurofilament Light Chains (NfL) or progranulin dosage to stratify treatment arms according to neuropathological substrates, and serum NfL dosage might be used to monitor the evolution of CBS. In this scenario, prospective cohort studies, starting with neurological examination and neuropsychological tests, should be considered to assess the correlations of clinical profiles and various biomarkers.

Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients. Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry. Results: sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant right ATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants. Conclusion: We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD.

We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression. A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans. Based on the genotype–phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment. This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation.

BACKGROUND: Traditional board games can entail significant skills encompassing several cognitive functions across different domains. Therefore, they may potentially represent effective cognitive interventions in the aging population with or without Alzheimer's disease or other types of dementia. OBJECTIVE: We aimed at verifying the hypothesis that traditional board games can prevent or slow down cognitive decline, through a systematic review on traditional board games and dementia. METHODS: We searched five databases with tailored search strings. We included studies assessing the impact of board games on elderly subjects at risk of or suffering from cognitive impairment, or subjects with cognitive impairment irrespective of age. Studies where the effect of board games was not separated by cards or other games were excluded. A meta-analysis was performed for specific cognitive and non-cognitive outcomes. RESULTS: Board games improved mental function, as measured by Montreal Cognitive Assessment (p = 0.003) and Mini-Mental State Examination (p = 0.02). Ska and Go improved Trail Making Test -A, while Mahjong improved executive functions. There was no consistent effect across different games on Digit Span or Categorical Fluency. Chess improved quality of life measured with the WHO-QoL-OLD scale (p < 0.00001). Mahjong temporarily improved depressive symptoms. Go increased BDNF levels and left middle temporal gyrus and bilateral putamen metabolism. CONCLUSIONS: Traditional board games may slow global cognitive decline and improve the quality of life in elderly subjects. Different games have varying impacts on specific cognitive domains, possibly mediated by functional and biological factors.

Background and ObjectivesMRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA).MethodsIn this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested.ResultsAs defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The

In individui con disturbi cerebrali sospetti o confermati, lo screening cognitivo tramite test performance-based convoglia informazioni di rilievo sia in termini diagnostici e prognostici che in ambito interventistico. Inoltre, tali test vengono spesso impiegati come misure di outcome nell’ambito di studi clinici aventi come oggetto la cognizione. Pertanto, gli screener cognitivi devono possedere solide caratteristiche statistiche e di usabilità. Tuttavia, nel panorama Italiano, gli screener cognitivi non sempre possiedono tali caratteristiche. Inoltre, in Italia, le pratiche di screening cognitivo da remoto sono state storicamente poco considerate, nonostante si prestino facilmente ad essere erogate a distanza tramite media di facile impiego, come il telefono. Tuttavia, avendo il potenziale di abbattere barriere geografiche, logistiche, socio-demografiche ed economiche, la disponibilità di screener cognitivi telefonici implicherebbe rilevanti vantaggi sia in ambito clinico che per l’implementazione e la portata a termine di studi clinici. In ragione di quanto suddetto, nelle prime due Sezioni della presente Dissertazione, in seguito ad una panoramica generale dei principi sottesi alle procedure di screening, viene fornita un’esauriente cornice per lo studio statistico degli screener cognitivi – affrontando 1) le loro applicazioni a fini di screening di popolazione e di case-finding nella pratica e ricerca cliniche, nonché le questioni relative a 2) proprietà clinimetriche (i.e., caratteristiche psicometriche e diagnostiche), 3) taratura (con un focus sul metodo dei Punteggi Equivalenti) e 4) usabilità trasversale/longitudinale. Inoltre, la Sezione 2 riporta una discussione dettagliata e critica 1) sul razionale, 2) su vantaggi e svantaggi e 3) sulle applicazioni cliniche/di ricerca degli screener cognitivi telefonici – focalizzandosi anche 4) sugli aspetti statistici relativi alla loro standardizzazione. Nella terza Sezione, in seguito ad una sinossi aggiornat, In individuals with suspected or confirmed brain disorders, cognitive screening via performance-based tests conveys pivotal information both towards diagnosis and prognosis and within interventional settings. Moreover, such tests are often employed as outcomes measures within clinical studies addressing cognition. Hence, cognitive screeners need to come with sound statistical and feasibility features. However, within the Italian scenario, cognitive screeners do not always present with such characteristics. Moreover, remote cognitive screening procedures have been historically underdeveloped in Italy, despite easily lending themselves to be delivered from a distance via practicable media, such as the telephone. However, by bridging down geographical, logistical, socio-demographic and economic barriers, the availability of telephone-based cognitive screeners would both entail improvements in healthcare settings and ease the implementation and accomplishment of clinical studies. Given the above premises, within the first two Sections of the present Dissertation, after outlining the principles underlying screening procedures in general, a comprehensive, practical framework for the statistical study of cognitive screeners is delivered – addressing 1) their applications for population-screening and case-findings aims within both clinical practice and research, as well as the issues of 2) clinimetrics (i.e., psychometrics and diagnostics), 3) norm derivation (with a focus on the Equivalent Score method) and 4) cross-sectional/longitudinal feasibility. In addition, Section 2 delivers an extensive, critical discussion on the 1) rationale, 2) benefits and shortcomings and 3) clinical/research applications of telephone-based cognitive screeners – also focusing on 4) the statistical issues related to their standardization. Within the third Section, after providing an up-to-date synopsis of the Italian status quo as to the statistical features of both in-person and telephone-bas

Behavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological and behavioral abnormalities seen in persons with dementia (PwD), significantly impacting their quality of life and that of their caregivers. Current assessment tools, such as the Neuropsychiatric Inventory (NPI), are limited by recall bias and lack of direct observation. This study aims to overcome this limitation by making caregiver reports more objective through the use of a novel instrument, referred to as the BPSDiary. This randomized controlled trial will involve 300 caregiver-PwD dyads. The objective is to evaluate whether the use of the BPSDiary could significantly reduce caregiver burden, assessed using the Zarit Burden Interview (ZBI), compared to usual care. The study will include adult PwD, caregivers living with or close to the patient, and BPSD related to the HIDA (hyperactivity, impulsivity, irritability, disinhibition, aggression, agitation) domain. Caregivers randomized to the intervention arm will use the BPSDiary to record specific BPSD, including insomnia, agitation/anxiety, aggression, purposeless motor behavior, and delusions/hallucinations, registering time of onset, severity, and potential triggers. The primary outcome will be the change in ZBI scores at 3 months, with secondary outcomes including changes in NPI scores, olanzapine equivalents, NPI-distress scores related to specific BPSD domains, and caregiver and physician satisfaction. The study will be conducted in 9 Italian centers, representing diverse geographic and sociocultural contexts. While potential limitations include the relatively short observation period and the focus on specific BPSD disturbances, the BPSDiary could provide physicians with objective data to tailor appropriate non-pharmacological and pharmacological interventions. Additionally, it may empower caregivers by encouraging reflection on BPSD triggers, with the potential to improve the quality of life for both PwD and t

Background: Analysis of subtypes of picture naming errors produced by patients with Alzheimer's disease (AD) have seldom been investigated yet may clarify the cognitive and neural underpinnings of naming in the AD spectrum. Objective: To elucidate the neurocognitive bases of picture naming in AD through a qualitative analysis of errors. Methods: Over 1000 naming errors produced by 70 patients with amnestic, visuospatial, linguistic, or frontal AD were correlated with general cognitive tests and with distribution of hypometabolism on FDG-PET. Results: Principal component analysis identified 1) a Visual processing factor clustering visuospatial tests and unrecognized stimuli, pure visual errors and visual-semantic errors, associated with right parieto-occipital hypometabolism; 2) a Concept-Lemma factor grouping language tests and anomias, circumlocutions, superordinates, and coordinates, correlated with left basal temporal hypometabolism; 3) a Lemma-Phonology factor including the digit span and phonological errors, linked with left temporo-parietal hypometabolism. Regression of brain metabolism on individual errors showed that errors due to impairment of basic and higher-order processing of object visual attributes or of their interaction with semantics, were related with bilateral occipital and left occipito-temporal dysfunction. Omissions and superordinates were linked to degradation of broad and basic concepts in the left basal temporal cortex. Semantic-lexical errors derived from faulty semantically- and phonologically-driven lexical retrieval in the left superior and middle temporal gyri. Generation of nonwords was underpinned by of phonological impairment within the left inferior parietal cortex. Conclusion: Analysis of individual naming errors allowed to outline a comprehensive anatomo-functional model of picture naming in classical and atypical AD.

Background: Reduced phonemic fluency is extremely frequent in progressive supranuclear palsy (PSP), but its neural correlate is yet to be defined. Objective: We explored the hypothesis that poor fluency in PSP might be due to neurodegeneration within a dominant frontal circuit known to be involved in speech fluency, including the opercular area, the superior frontal cortex (BA6), and the frontal aslant tract connecting these two regions. Methods: We correlated performance on a letter fluency task (F, A, and S, 60 s for each letter) with brain metabolism as measured with Fluoro-deoxy-glucose Positron Emission Tomography, using Statistical Parametric Mapping, in 31 patients with PSP. Results: Reduced letter fluency was associated with significant hypometabolism at the level of left BA6. Conclusion: Our finding is the first evidence that in PSP, as in other neurogical disorders, poor self-initiated, effortful verbal retrieval appears to be linked to dysfunction of the dominant opercular-aslant-BA6 circuit.

Hallucinations are common in neurodegenerative dementias, being present in a significant proportion of patients. Most of the available studies show that acetylcholinesterase inhibitors may be beneficial in preventing and treating hallucinations in patients with neurodegenerative and even psychiatric disorders, even though there are reports that they might also develop as an adverse effect of such therapy. However, a clear causal relationship for the latter association was not previously established. Here we describe 2 cases of patients treated with donepezil who developed complex multimodal hallucinations, which could be causally linked to the drug by means of a challenge-dechallenge (and rechallenge in one case) paradigm. We also provide a narrative review of the literature regarding donepezil and hallucinations and propose a hypothesis to explain the occurrence of this phenomenon.

Background: This study compares the performance at the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) across the healthy adult lifespan in an Italian population sample. Methods: The MMSE and MoCA were administered to 407 Italian healthy native-speakers (165 males; age range 20–93 years; education range 4–25 years). A generalized Negative Binomial mixed model was run to profile MMSE and MoCA scores across 8 different age classes (≤ 30; 31–40; 41–50; 51–60; 61–70; 71–80; 81–85; ≥ 86) net of education and sex. Results: MMSE and MoCA total scores declined with age (p < 0.001), with the MoCA proving to be “more difficult” than the MMSE (p < 0.001). The Age*Test interaction (p < 0.001) indicates that the MoCA proved to profile a sufficiently linear involutional trend in cognition with advancing age and to be able to detect poorer cognitive performances in individuals aged ≥ 71 years. By contrast, MMSE scores failed in capturing the expected age-related trajectory, reaching a plateau in the aforementioned age classes. Discussion: The MoCA seems to be more sensitive than the MMSE in detecting age-related physiological decline of cognitive functioning across the healthy adult lifespan. The MoCA might be therefore more useful than the MMSE as a test for general cognitive screening aims.

Tic related disorders affect 4–20% of the population, mostly idiopathic, can be grouped in a wide spectrum of severity, where the most severe end is Tourette Syndrome (TS). Tics are arrhythmic hyperkinesias to whom execution the subject is forced by a “premonitory urge” that can be classified as sensory tic, just-right experience or urge without obsession. If an intact volitional inhibition allows patients to temporarily suppress tics, a lack or deficit in automatic inhibition is involved in the genesis of the disorder. Studies have assessed the presence of intrinsic microscopic and macroscopic anomalies in striatal circuits and relative cortical areas in association with a hyperdopaminergic state in the basal forebrain. Prepulse inhibition (PPI) of the startle reflex is a measure of inhibitory functions by which a weak sensory stimulus inhibits the elicitation of a startle response determined by a sudden intense stimulus. It is considered an operation measure of sensorimotor gating, a neural process by which unnecessary stimuli are eliminated from awareness. Evidence points out that the limbic domain of the CSTC loops, dopamine and GABA receptors within the striatum play an important role in PPI modulation. It is conceivable that a sensorimotor gating deficit may be involved in the genesis of premonitory urge and symptoms. Therefore, correcting the sensorimotor gating deficit may be considered a target for tic-related disorders therapies; in such case PPI (as well as other indirect estimators of sensorimotor gating) could represent therapeutic impact predictors.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer’s disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment.

Background: This study aimed to provide equating norms for the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) from a sample of healthy Italian adults. Methods: Four-hundred and seven Italian healthy adults (165 males, 242 females; mean age = 60.61 ± 13.74 years, range= 20–93; mean education = 12.2 ± 4.42 years, range= 4–25) were administered the MMSE and the MoCA. ‘MMSE-to-MoCA’ and ‘MoCA-to-MMSE’ conversion tables were derived via log-linear smoothing equi-percentile equating (LSEE). Equivalence between empirical and conversion-derived scores was determined with a two one-sided test (TOST) procedure. Results: Conversion-derived scores were statistically equivalent to empirical ones for both the MMSE (p = 0.948) and the MoCA (p = 0.437). The LSEE yielded impossible/unreliable conversion estimates for floor scores on both tests, whereas conversions for uppermost scores were highly consistent. Discussion: The present data will help avoid inter-rater heterogeneity in cross-sectionally and longitudinally adopting either one of the two cognitive screening tests, and to retrospective analyze data collected via either one test or the other.

Background: Cognitive screening tests (CSTs) are crucial to neuropsychological diagnostics, and thus need to be featured by robust psychometric and diagnostic properties. However, CSTs happen not to meet desirable statistical standards, negatively affecting their level of recommendations and applicability. This study aimed at (a) providing an up-to-date compendium of available CSTs in Italy, (b) report their psychometric and diagnostic properties, and (c) address related limitations. Methods: This review was implemented by consulting Preferred Reporting Items for Systematic Reviews and Meta-Analyses and pre-registered on the International Prospective Register of Systematic Reviews. Standardization and usability studies focusing on norms, validity, reliability, or sensitivity/specificity (and derived metrics) in adults were considered for eligibility. Quality assessment was performed by means of an ad hoc checklist collecting information on sampling, psychometrics/diagnostics, norming, and feasibility. Results: Sixty studies were included out of an initial N = 683. Identified CSTs (N = 40) were classified into general, domain-, and disease-specific (N = 17, 7, and 16, respectively), the latter being less statistically robust than remaining categories. Validity and reliability evidence was provided for 29 and 26 CSTs, respectively, sensitivity/specificity for 20 and norms for 33. Prevalence- and post-test-based diagnostic metrics were seldomly represented; factorial structures, ceiling/floor effects, and acceptability rarely investigated; content, face, and ecological validity never assessed. Discussion: Although available Italian CSTs overall met basic psychometric/diagnostic requirements, their statistical profile often proved to be poor on several properties that are desirable for clinical applications, with a few exceptions among general and domain-specific ones.

Background: Deficits of executive functioning (EF) are frequently found in neurological disorders. The Frontal Assessment Battery (FAB) is one of the most widespread and psychometrically robust EF screeners in clinical settings. However, in Italy, FAB norms date back to 15 years ago; moreover, its validity against “EF-loaded” global cognitive screeners (e.g., the Montreal Cognitive Assessment, MoCA) has yet to be tested. This study thus aimed at (a) providing updated normative data for the Italian FAB and (b) assessing its convergent validity with the MoCA. Methods: Four-hundred and seventy-five healthy Italian native speakers (306 females, 169 males; mean age: 61.08 ± 15.1; mean education: 11.67 ± 4.57) were administered by the MoCA and the FAB. FAB items were divided into three subscales: FAB-1 (linguistically mediated EF), FAB-2 (planning), and FAB-3 (inhibition). Regression-based norms were derived (equivalent scores) for all FAB measures. Results: Age and education were predictive of all FAB measures, whereas no gender differences were detected. The FAB and its sub-scales were related to MoCA measures—the strongest associations being found with MoCA total and MoCA-EF scores. FAB sub-scales were both internally related and associated with FAB total scores. Discussion: The FAB proved to have convergent validity with both global cognitive and EF measures in healthy individuals. The present study provides updated normative data for the FAB and its sub-scales in an Italian population sample, and thus supports an adaptive usage of this EF screener.

Background: The availability of fine-grained, culture-specific psychometric outcomes can favor the interpretation of scores of the Montreal Cognitive Assessment (MoCA), the most frequently used instrument to screen for mild cognitive dysfunctions in both instrumental and non-instrumental domains. This study thus aimed at providing: (i) updated, region-specific norms for the Italian MoCA, by also (ii) comparing them to pre-existing ones with higher geographical coverage; (iii) information on sensitivity and discriminative capability at the item level. Methods: Five hundred and seventy nine healthy individuals from Northern Italy (208 males, 371 females; age: 63.4 ± 15, 21–96; education: 11.3 ± 4.6, 1–25) were administered the MoCA. Item Response Theory (IRT) was adopted to assess item difficulty and discrimination. Normative values were derived by means of the Equivalent Scores (ESs) method, applied to the MoCA and its sub-scales. Average ESs were also computed. Agreement with previous ESs classification was assessed via Cohen’s k. Results: Age and education significantly predicted all MoCA measures except for Orientation, which was related to age only. No sex differences were detected when tested along with age and education. Substantial disagreements with previous ESs classifications were detected. Several items proved to be scarcely sensitive, especially the place item from Orientation and the letter detection task. Memory items showed high discriminative capability, along with certain items assessing executive functions and orientation. Discussion: Item-level information herewith provided for the Italian MoCA can help interpret its scores by Italian practitioners. Italian practitioners should consider an adaptive use of region-specific norms for the MoCA.

Introduction: Neurological soft signs (NSS) are subtle non-localizing sensorimotor abnormalities initially reported as increased in primary headache patients. The aims of this study were confirming with full power NSS increased expression in migraine and, collaterally, determining if psychiatric traits or white matter lesions at brain imaging could influence this result. Methods: Forty drug-free episodic migraine outpatients (MH) were recruited with 40 matched controls. NSS were determined by the 16-item Heidelberg scale; depression, anxiety and QoL by the HAM-D; the STAI-X1/X2; and the SF36, respectively. The Fazekas scale on brain MR studies was applied in n = 32 MH, unravelling deep white matter signal alterations (DWM). MH characteristics, including the headache disability inventory (HDI), were recorded. Results: NSS were 46% increased in MH vs. controls (p = 0.0001). HAM-D and STAI-X1/X2 were increased in MH, while SF36 was unchanged, but they all failed to influence NSS, just as MH characteristics. NSS scores were increased in MH-DWM + (n = 11, + 85%) vs. MH-DWM − (n = 21, + 27%) vs. controls (p < 0.0001). NSS increased expression in MH was influenced by DWM, while psychiatric traits and headache characteristics failed to do so. Discussion/conclusions: NSS are increased in MH and probably not influenced by the affective status, possibly marking a dysfunction within the cerebellar-thalamic-prefrontal circuit that may deserve further attention from the prognostic point of view.