BACKGROUND:This study aimed at identifying neuropsychological sub-phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks. METHODS:We used individual task-/item-level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non-demented ALS to derive neuropsychological sub-phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo-spatial measures. RESULTS:The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub-phenotypes were identified: dysexecutive MCI-single- and multiple-domain (dMCI-sd: 63%; dMCI-md: 24%, respectively); non-dysexecutive MCI-single- and multiple-domain (ndMCI-sd: 12%; ndMCI-md: 1%, respectively). MBI was classified as follows: apathetic MBI-single- and multiple-domain (aMBI-sd: 40%; aMBI-md: 20%, respectively); apathetic-disinihibited/perseverative MBI-multiple domain (ad/pMBI-md: 21%); disinihibited/perseverative MBI-multiple domain (d/pMBI-md: 7%); psychotic MBI-single- and multiple-domain (psyMBI-sd: 2%; psyMBI-md: 3%, respectively); unclassifiable MBI-multiple domain (uMBI-md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI). CONCLUSIONS:This study delivers a provisional, ECAS-based classification for the neuropsychological sub-phenotyping of non-demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.

Social cognition, essential for interpreting and responding to social contexts, is frequently impaired in neurological and psychiatric disorders. Multiple brain regions, organized in large-scale brain networks, represent the neurobiological substrate of social cognitive abilities, and are the main target of neurodegeneration in the fronto-temporal dementia spectrum. The focus of this review is a specific anatomic subcomponent of these networks, i.e. the amygdalo-hippocampal complex (AHC). Animal models suggest that the AHC is involved in processes underlying social cognition through both localized mechanisms and integration within large-scale networks. In humans, AHC pathology in conditions such as Alzheimer's disease (AD), epilepsy, and autoimmune encephalitis (AIE) has been associated with social cognition impairment. In AD and Mild Cognitive Impairment (MCI) deficits in Theory of Mind (ToM), empathy, and emotion recognition are common and linked to medial temporal atrophy. In focal frontal and temporal lobe epilepsy, seizures and interictal dysfunctions disrupt social cognition, particularly ToM, from early stages. In AIE, marked fear recognition deficits are closely related to amygdala involvement. These conditions highlight the association between social cognition impairments and damage to the AHC. From a theoretical perspective, investigating the relationship between the AHC and social cognition may advance our understanding of the neurobiological underpinnings of social behavior. Clinically, the systematic assessment of social cognition in patients with conditions affecting the AHC appears warranted, potentially improving diagnosis, prognostic evaluation, and therapeutic strategies.

BackgroundBoth anterograde and retrograde amnesia can typically co-occur in limbic autoimmune encephalitis (LAE), including the forms associated with antibodies to CASPR2/LGI1, two protein complexed with the voltage-gated potassium channel (VGKC). However, isolated retrograde amnesia is very rare, and it has never been described in LAE.MethodsWe report two patients with CASPR2 LAE who showed isolated retrograde amnesia, without other significant cognitive impairments. A systematic literature review was performed in accordance with the PRISMA guidelines on patients with LAE, antibodies to the VGKC complex (including LGI1, CASPR2, or the VGKC), and memory impairment.ResultsWe identified 467 patients from 29 studies. Fourteen/467 had retrograde amnesia (2.9%), which co-occurred with anterograde amnesia in 12 with VGKC antibodies (7 with LGI1 LAE-like clinical phenotypes). Our two cases with CASPR2 LAE (2/469, 0.4%) were the only ones with isolated retrograde amnesia, which was actively investigated in only 56/467 patients. Thirteen/14 patients, including the two with isolated retrograde amnesia, had partial or poor cognitive improvement.ConclusionsRetrograde amnesia is rare but likely under-recognized in VGKC-complex antibodies LAE and associates with poor recovery. When isolated, it adds to the spectrum of CASPR2 LAE. These findings promote insights into retrograde amnesia pathophysiology, deserving investigation across the whole spectrum of AE.

This national expert-based Delphi-consensus aims at formulating recommendations on the management of dementia care in Italy. This effort seems important and timely given in light of a new scenario arising from a new biological definition of Alzheimer’s disease (AD) and the availability of disease-modifying treatments (DMTs). the Steering Committee of the Italian Neurological Society for dementia (SINdem) created appropriate statements. Invited SINdem experts were requested to vote on the statements according to a modified three-round Delphi method. Only those statements reaching Grade A (full agreement ≥ 75

BACKGROUND:The Three-Objects-Three-Places (3O3P) test is a 5-min screen for episodic memory impairment due to Alzheimer's disease, known for its briefness and easy administration, culture- and language-free nature, and the absence of specific equipment. However, no studies have validated its potential in memory clinic cohorts. The aim of this study was to test its convergent, discriminant, and known-group validities and to define thresholds for its clinical use. METHODS:We included 2062 cognitively unimpaired (CU), mild cognitive impairment (MCI) and dementia patients from the Geneva Memory Center cohort who underwent the 3O3P test in the context of clinical practice. Convergent and discriminant validities were assessed using an exploratory factor analysis. The known-group validity was assessed in CU vs. MCI and dementia using the area under the curve (AUC). 3O3P test scores vs. amyloid and tau positivity, neurodegeneration, and cognition (ATNC) were assessed using the Kruskal-Wallis test. The 3O3P test cut-offs were calculated using sensitivity, specificity, PPV, NPV, and accuracy. RESULTS:Mean age was 72 years (SD = 11), 60% were female, mean education was 13 years (SD = 4), and mean MMSE was 25 (SD = 5). The 3O3P and Delayed Total Recall tests loaded strongly on the "memory" factor and weakly on "non-memory" factors. The 3O3P test can discriminate CU vs. MCI (AUC = 0.71) and dementia (AUC = 0.92). Higher 3O3P scores were associated with lower prevalence of ATNC (p < 0.001). A 3O3P value of 7 can detect MCI and dementia patients. CONCLUSIONS:The 3O3P test has demonstrated good convergent, discriminant, and known-group validity in a large memory clinic population.

Metacognition may give useful insight in early stages of Alzheimer’s disease (AD) continuum. Recent studies suggest differences in the ability of judging their own cognitive performance along clinical stages. For instance, subjects with mild cognitive impairment (MCI) overestimate, whereas people with subjective cognitive decline (SCD) tend to underestimate their cognitive performance. One cognitive function compromised in prodromal AD is prospective memory (PM), which refers to the ability to remember something that has to be done. However, the metacognitive abilities in PM tasks are still not clear when comparing individuals with varying degrees of cognitive impairment. Our study included 94 subjects from the Geneva Memory Center which are cognitively unimpaired (CU; n = 53), SCD (n = 26), and MCI (n = 15). All subjects performed a PM task with judgements of learning (JOL) to evaluate their metacognition. For that, participants were instructed to memorize a list of pairs of words and to press a specific key if the first word of the pair appeared in a posterior lexical decision task. A one-way ANOVA tested the differences in PM performance and corresponding JOLs among the three clinical groups. Lastly, the association of PM metacognition with subjective complaints and anxiety levels was tested using Pearson correlations. The PM ability was significantly different among clinical groups (F = 10.5, p<0.001). Post-hoc analysis revealed that MCI showed significantly lower PM in comparison with CU (p<0.001) and SCD (p = 0.003). Moreover, the JOL of PM also differed among the three groups (F = 4.5, p = 0.02), namely the MCI group showed lower JOLs in comparison with CU (p = 0.04). Likewise, correlations suggested a significant association between PM-JOLs and subjective complaints (self-other; R = 0.33, p = 0.006), whereas the association with anxiety was not statistically significant (p>0.05). Our study suggested differences in the PM and its JOL between MCI and CU/SCD. However, our study was not able to differentiate between the CU and SCD groups at the PM and the corresponding JOL, even though their difference was significantly correlated with subjective functioning.

The differential diagnosis between Alzheimer’s disease (AD) and other causes of dementia is essential but challenging. Therefore, there is an increasing need for early, reliable, and non-invasive tests to distinguish between different forms of dementia. To determine whether neuropsychological tests assessing visuospatial function can improve confidence in the clinical diagnosis of AD. Retrospective observational single-center cohort study involving all patients consecutively referred to our outpatient clinic for cognitive disorders who underwent neuropsychological assessment between 2013 and 2018. In addition to demographic and functional variables, each patient underwent neuropsychological tests to assess cognitive performance, memory, and executive, language, and visuospatial ability, according to clinical protocols. The clinical diagnosis of cognitive disorders, based on standard diagnostic criteria, served as the gold standard. Accuracy measures of visuospatial tests to diagnose AD were calculated. Additionally, a new index derived from the sum of four items (Rey-Osterrieth figure copying, Copy of Drawings, Clock Drawing Test, and years of schooling) was tested (ReDCOOL). Of the 342 patients analyzed, 308 were diagnosed with dementia or mild cognitive impairment, including 60 with AD. AD patients exhibited the worst performance in visuospatial tests, and the utilization of the ReDCOOL index proved to be more dependable in identifying AD compared to other tests (AUROC 0.729, 95

Background: The embodied cognition approach, as applied to concrete knowledge, is centred on the role of the perceptual and motor aspects of experience. To extend the embodied framework to abstract knowledge, some studies have suggested that further dimensions, such as affective or social experiences, are relevant for the semantic representations of abstract concepts. The objective of this study is to develop a measure that can quantitatively capture the multidimensional nature of abstract concepts. Methods: We used dimension-rating methods, known to be suitable, to account for the semantic representations of abstract concepts, to develop a new database of 964 Italian words, rated by 542 participants. Besides classical psycholinguistic variables (i.e., concreteness, imageability, familiarity, age of acquisition, semantic diversity) and affective norms (i.e., valence, arousal), we collected ratings on selected dimensions characterizing the semantic representations of abstract concepts, i.e., introspective, mental state, quantitative, spatial, social, moral, theoretical, and economic dimensions. The measure of exclusivity was incorporated to quantify the number of dimensions, and the respective relevance, for each concept. Concepts with a high value of exclusivity rely on only one/a few dimension/s with high value on the respective rating scale. Results: A multidimensional representation characterized most abstract concepts, with two robust major clusters. The first was characterized by dense intersections among introspective, mental state, social, and moral dimensions; the second, less interconnected, cluster revolved around quantitative, spatial, theoretical, and economic dimensions. Quantitative, theoretical, and economic concepts obtained higher exclusivity values. Conclusions: The present study contributes to the investigation of the semantic organization of abstract words and supports a controlled selection and definition of stimuli for clinical and research settings.

INTRODUCTION:Knowledge gaps remain about the prognosis of mild cognitive impairment (MCI). Conversion rates to dementia vary widely, and reversion to normal cognition has gained attention. This review updates evidence on MCI conversion risk and probability of stability and reversion. METHODS:We searched databases for studies on MCI prognosis with ≥3 years of follow-up, established criteria for MCI and dementia, and performed a meta-analysis using a random-effects model to assess conversion risk, reversion, and stability probability. Meta-regressions identified sources of heterogeneity and guided subgroup analysis. RESULTS:From 89 studies (mean follow-up: 5.2 years), conversion risk was 41.5% (38.3%-44.7%) in clinical and 27.0% (22.0%-32.0%) in population-based studies, with Alzheimer's dementia as the most common outcome. Stability rates were 49.3% (clinical) and 49.8% (population). Reversion was 8.7% (clinical) and 28.2% (population). DISCUSSION:Our findings highlight higher conversion in clinical settings and 30% reversion in population studies, calling for sustainable care pathway development. Highlights:Prognosis for mild cognitive impairment (MCI) varies by setting; dementia risk is higher and the probability of reversion is lower in clinical-based studies.In both clinical and population settings, cognitive stability is ≈50%.A reorganization of health services could ensure sustainable care for individuals with MCI.Significant heterogeneity in MCI studies impacts data interpretation; follow-up length is crucial.Long-term prognosis studies on MCI in low- and middle-income countries are urgently needed.

The COVID-19 pandemic has accelerated the adoption of digital health technologies across disciplines, including clinical neuropsychology, where accessible and efficient platforms for cognitive diagnosis and monitoring are needed. However, limited user-friendliness often prevents their use, particularly among the elderly. Few studies have explored usability (Us) and user experience (UX) of teleneuropsychology platforms in real-world clinical settings. This study reports Us and UX data of a certified tablet-based teleneuropsychology platform developed for mild cognitive impairment (MCI) detection. Examiner and User interfaces were evaluated respectively by clinical neuropsychologists (n = 15, mean age 29.7 ± 3.8 years) and healthy volunteers (n = 15, mean age 58 ± 8.1 years). Us and UX were assessed using validated questionnaires: System Usability Scale (SUS), Post-Study System Usability Questionnaire (PSSUQ), Telehealth Usability Questionnaire (TUQ), and User Experience Questionnaire (UEQ). Familiarity with technology was measured using the Information Technology Familiarity Questionnaire (ITF). Non-parametric tests compared Us, UX, and ITF scores between groups; correlation analyses explored associations between demographic variables and questionnaire outcomes. Both groups showed good-to-excellent Us and UX, with no significant differences between them. Technology familiarity was significantly higher in the Examiner group. Correlation analyses revealed significant associations between ITF scores and demographic variables, with younger and more educated individuals reporting better familiarity. This study emphasise how intuitive design and engaging interfaces, like those of the tested platform, can mitigate technological barriers in sensitive context and foster acceptance, even among older users with lower digital familiarity. Future work should refine usability metrics, develop standardized teleneuropsychology guidelines, and promote digital literacy.

BACKGROUND:This study aimed at assessing the applicability of a symptom-led staging system for primary progressive aphasia (PPA) based on retrospective medical records, as well as at exploring their demographic and clinical correlates. METHODS:75 PPA patients (10 semantic, 28 non-fluent, 22 logopenic, and 16 mixed variants) were retrospectively staged according to the PPA Progression Planning Aid (PPA-Squared) system, which stages the disease by accounting for clinical features along three axes: (1) Communication; (2) Non-Verbal Thinking and Personality; (3) Personal Care and Well-Being. The percentage of successfully staged patients was computed. The association between PPA-Squared scores and demographic and clinical data was tested via non-parametric tests. The predictive capability of PPA-Squared scores towards survival was explored via a Mantel-Cox test. RESULTS:89.3% of patients were successfully staged based on retrospective medical records. The PPA-Squared was associated with the MMSE (p < 0.001), ADL (p = 0.021), and IADL scores (p < 0.001) and a set of second-level cognitive measures tapping on attention, executive functions, language, long-term memory, and visuo-spatial abilities (p ≤ 0.049). No association was found between the PPA-Squared and demographic features, symptom duration, PPA phenotype, the presence of motor involvement, and survival. DISCUSSION:The PPA-Squared is a feasible and clinically valid tool for staging PPA patients based on their cognitive and functional status.

Harmonized neuropsychological assessment for neurocognitive disorders (NCDs) is an urgent priority in clinics. Neuropsychology assessments in NCDs seldom include tests exploring social cognitive skills. In 2022, we launched the SIGNATURE initiative to optimize socio-cognitive assessment in NCDs. Here, we report findings from the first initiative phase, including consortium creation and evaluation of the state of the art in socio-cognitive assessment in memory clinics. We developed an ad hoc online survey to explore practices and measures, relevance, and obstacles preventing the use of socio-cognitive testing in clinics. The survey was distributed within the SIGNATURE network. National coordinators were identified to disseminate the survey to local collaborators and scientific societies active in the field of dementia and/or neuropsychology. Data were analysed in aggregate form and stratified by geographical area and variables of interest. Four hundred and thirteen (413) responses from 10 European and Latin American geographical regions were recorded. Responders were balanced between physicians and psychologists. Seventy-eight (78) % of respondents reported no/limited experience with socio-cognitive measures; more than 85% agreed on their relevance in clinics. Ekman-60 faces was the most well-known and/or used task, followed by the Faux-Pas and Reading-the-Mind-in-the-Eyes tests. Lack of clinical measures, assessment time, guidelines, and education/training were reported as main obstacles. Real-life barriers prevent the adoption of socio-cognitive testing in clinics. Bidirectional collaboration between clinicians and researchers is required to address clinical needs and constraints and facilitate consistent socio-cognitive assessment.

BACKGROUND AND OBJECTIVES:Diagnosing the different variants of primary progressive aphasia (PPA) is challenging, but more accurate characterization can improve patient management and treatment outcomes. This study aimed to identify the following: (1) which speech features, alone or combined with language assessment and gray matter volumes (GMVs), best distinguish PPA variants and (2) how connected speech evolves in PPA. METHODS:This prospective study was conducted at IRCCS San Raffaele Hospital in Milan, Italy, between 2010 and 2021. We included patients with PPA who underwent neuropsychological assessments, including standard evaluation of language and the "Picnic Scene" speech test, and, when available, brain structural MRI. Clinical and language assessments were also performed at follow-up in a subgroup. Sequential feature selection models identified speech parameters that best differentiated groups, incorporating age, sex, education, standard language tests, and GMVs. In each PPA group, linear mixed-effect models analyzed speech changes over time. RESULTS:We included 95 patients with PPA (mean age 69 ± 9 years, 55 women [58%]; 40 with nonfluent variant PPA [nfvPPA], 35 with semantic variant PPA [svPPA], 20 with logopenic variant PPA [lvPPA]), of whom 82 underwent brain MRI and 34 had a follow-up visit after 10.2 months. Each model distinguished svPPA from the other PPA groups with high accuracy (R2 range 0.93-1.00; p < 0.001). No differences in accuracy were observed among models for this distinction. In differentiating nfvPPA and lvPPA groups, the models incorporating speech parameters (R2 = 0.92; p < 0.001), GMVs (R2 = 0.95; p < 0.001), and their combination (speech + GMVs; R2 = 0.97; p < 0.001) outperformed those using only standard language scores (R2 = 0.75; p = 0.01). Over time, patients with nfvPPA showed more phonological errors, the svPPA group exhibited more semantic and morphosyntactic errors along with difficulties in naming and syntax production, and patients with lvPPA exhibited reduced number of words per second and fewer words per sentence. DISCUSSION:All models were equally effective in distinguishing the svPPA group from the other 2 PPA subtypes. However, compared with using standard measures alone, incorporating speech measures from the "Picnic Scene" speech test, GMVs, or their combination into the models significantly improved accuracy in differentiating nfvPPA and lvPPA groups. The PPA variants showed distinct speech trajectories. These variables can aid in understanding disease progression, predicting patient outcomes, and planning speech therapy interventions in clinical practice.

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.

To identify: (i) which features of speech (alone or in combination with standard language tests and/or brain gray matter [GM] volumes) most effectively distinguish primary progressive aphasia (PPA) variants; (ii) how spontaneous speech evolved over time, and (iii) the best combination of features predicting speech evolution in each PPA variant.

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.

The Italian telephone-based Mini-Mental State Examination (Itel-MMSE) is considered a very easy tool for screening individuals with dementia, gained importance during COVID-19, but lacks validation and faces a ceiling effect. In the present study, we conducted a study standardizing and validating it, establishing cut-off values for two versions. Across 24 Italian sites, 707 healthy individuals (50–89 years, men: 268, women: 439) with diverse educational levels (3–24 years) were recruited. Subjects met criteria for normal conditions investigated through a semi-structured interview covering neurological, psychiatric, general medical, and psychopharmacological history. Two test versions were created to assess test–retest reliability at 45-day intervals. We also enrolled 187 subjects with Mild Cognitive Impairment (MCI) and 181 with Alzheimer's Disease (AD) for validation. The raw scores obtained on both versions of Itel-MMSE were set as dependent variables in linear regression models that included age, education, and gender as independent variables. Mean raw Itel-MMSE1 score was 20.82 (range: 13–22). Multiple linear regression demonstrated significant effects of sociodemographic variables for age and education, establishing a new cut-off ≥ 18.49. Mean raw Itel-MMSE2 score was 20.97 (range: 10–22), with a new cut-off ≥ 18.45. Validation showed high informative values, with areas under the curve (AUCs) for MCI and AD conditions and both versions (Itel-MMSE1: MCI AUC = 0.801, AD AUC = 0.907; Itel-MMSE2: MCI AUC = 0.827, AD AUC = 0.977). The Itel-MMSE proves valuable as a screening method for detecting and monitoring dementia in remote phone screenings, with different cut-offs aiding MCI patient identification in clinical settings.

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.

The COVID-19 pandemic has given rise to post-acute cognitive symptoms, often described as ‘brain fog’. To comprehensively grasp the extent of these issues, we conducted a study integrating traditional neuropsychological assessments with experimental cognitive tasks targeting attention control, working memory, and long-term memory, three cognitive domains most commonly associated with ‘brain fog’. We enrolled 33 post-COVID patients, all self-reporting cognitive difficulties, and a matched control group (N = 27) for cognitive and psychological assessments. Our findings revealed significant attention deficits in post-COVID patients across both neuropsychological measurements and experimental cognitive tasks, evidencing reduced performance in tasks involving interference resolution and selective and sustained attention. Mild executive function and naming impairments also emerged from the neuropsychological assessment. Notably, 61% of patients reported significant prospective memory failures in daily life, aligning with our recruitment focus. Furthermore, our patient group showed significant alterations in the psycho-affective domain, indicating a complex interplay between cognitive and psychological factors, which could point to a non-cognitive determinant of subjectively experienced cognitive changes following COVID-19. In summary, our study offers valuable insights into attention challenges faced by individuals recovering from COVID-19, stressing the importance of comprehensive cognitive and psycho-affective evaluations for supporting post-COVID individuals.

Background Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce. Methods Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients’ linguistic performance in a shared space. Patients had been studied with [ 18 F] FDG-PET. Correlations were performed between metabolic and behavioral data. Results Patients’ profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space. Discussion Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups.