A digital teleneuropsychology platform for the diagnosis of mild cognitive impairment: from concept to certification as a medical device.

BACKGROUND: Innovative digital solutions are shaping a new concept of dementia care, opening additional venues for prevention, diagnosis, monitoring and treatment. Hereby, we report the development of a tablet-based teleneuropsychology platform (Tenèpsia®), from concept to certification as Medical Device (MD) Class IIA, as per new MD regulation 745/2017. METHODS: The platform was designed for the remote cognitive evaluation and created thanks to the effort of a collaborative working group including experts from three Italian scientific societies and Biogen Italia S.r.l. (hereafter "Biogen"), and developers from Xenia Reply and Inside AI. The development strategy was guided by converting traditional paper-and-pencil tests into digital versions while maintaining comparable neuropsychological features and optimizing patient accessibility and user experience. The experts focused on the choice and adaptation of traditional neuropsychology measures for a 45-min teleneuropsychology assessment. RESULTS: The developers created a web and a mobile interface, respectively, for the professional (neuropsychologist) and non-professional (patient and caregiver) use. Recording of voice, drawing and typing information was enabled. Instant dashboards provide a quick overview of the patient's condition. Simulation activities were performed to obtain MD certification, valid across Europe. CONCLUSION: Neuropsychology services will benefit from the implementation in clinics of harmonized digital tools with adequate scientific and technological standards. The use of digital cognitive testing for the diagnosis of mild cognitive impairment is expected to enhance patient and clinician outcomes through simplified, digital objective data collection, sparing of time and resources, with a positive impact on healthcare costs and access to treatments, reducing inequalities and delays in diagnosis and cure.

TACO: A Turkish database for abstract concepts.

The organization of abstract concepts reflects different dimensions, grounded in the brain regions coding for the corresponding experience. Normative measures of linguistic stimuli offer noteworthy insights into the organization of conceptual knowledge, but studies differ in the dimensions and classes of concepts considered. Additionally, most of the available information has been collected in English, without considering possible linguistic and cultural differences. Here, we aimed to create a comprehensive Turkish database for abstract concepts (TACO), including rarely investigated classes such as political concepts. We included 503 words-78 concrete (fruits, animals, tools) and 425 abstract (emotions, social, mental states, theoretical, quantity, space, political)-rated by 134 Turkish speakers for familiarity, imageability, age of acquisition, valence, arousal, quantity, space, theoretical, social, mental state, and political dimensions. We calculated dominance and exclusivity, indicating the dimension receiving the highest mean score for each word, and the position of the word along the unidimensional-multidimensional continuum, respectively. A principal component analysis (PCA) was conducted on the semantic dimensions. The results showed that mental state was the dominant dimension for most concepts. Moderate to low levels of exclusivity indicated that the concepts were multidimensional. PCA revealed three components: Component 1 captured the juxtaposition between social/mental state and magnitude polarities, Component 2 highlighted affective components, and Component 3 grouped together political and theoretical dimensions. The introduction of political concepts provided insights into the multidimensional nature of this unexplored class, closely intertwined with the theoretical dimension. TACO constitutes the first comprehensive Turkish database covering several abstract dimensions, paving the way for cross-linguistic and cross-cultural studies of semantic representations.

Italian Dementia-Friendly Hospital Trial (IDENTITÀ): efficacy of a dementia care intervention for hospital staff.

This study investigated the short-term impact and the retention of a dementia care intervention for healthcare staff working in an Italian acute hospital setting. Additionally, we identified the predictors of improvement across the intervention.Sixty-two healthcare staff from an Italian public hospital participated in a dementia care intervention consisting of 5 modules delivered in a 5-hour training program focusing on dementia management, knowledge, and care. A pre-test/post-test and six-months follow-up design was used to evaluate participants' changes in knowledge, attitudes, and confidence in dementia.The intervention significantly improved healthcare staff's dementia knowledge and confidence immediately after the end of the intervention. No significant changes were observed from post-test to follow-up, indicating retention of these outcomes over six months. Regarding attitude to dementia, we found an immediate improvement only in the Recognition of Personhood scale. Looking at the predictors of improvement, healthcare staff with lower levels of knowledge, attitudes, and confidence in dementia at pre-test were those who improved more following the intervention.These findings provide further evidence that dementia care interventions are suitable initiatives to promote knowledge and skills required to manage the needs of people with dementia in an acute hospital setting.

Feasibility of a standard cognitive assessment in European academic memory clinics.

INTRODUCTION: Standardized cognitive assessment would enhance diagnostic reliability across memory clinics. An expert consensus adapted the Uniform Dataset (UDS)-3 for European centers, the clinician's UDS (cUDS). This study assessed its implementation acceptability and feasibility. METHODS: We developed a survey investigating barriers, facilitators, and willingness to implement the cUDS. With a mixed-methods design, we analyzed data from academic memory clinics. RESULTS: Seventy-eight percent of responding clinicians were experienced neuropsychologists/psychologists and 22% were medical specialists coming from 18 European countries. Sixty-five percent clinicians were willing to implement cUDS. General barriers related to implementation (43%) and clinical-methodological domains (21%). Favorable clinicians reported finances (15%) and digitalization (9%) as facilitating, but unavailability of local norms (23%) as hindering. Unfavorable clinicians reported logistical (23%) and time issues (18%). DISCUSSION: Despite challenges, data showed moderate clinicians' acceptability and requirements to improve feasibility. Nonetheless, these results come from academic clinicians. The next steps will require feasibility evaluation in non-academic contexts.

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus.

INTRODUCTION: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome. METHODS: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria. RESULTS: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes. DISCUSSION: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

European consensus for the diagnosis of MCI and mild dementia: Preparatory phase.

INTRODUCTION: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. METHODS: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. RESULTS: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). DISCUSSION: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers' use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. HIGHLIGHTS: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.

Emotion Recognition Deficits in the Differential Diagnosis of Amnestic Mild Cognitive Impairment: A Cognitive Marker for the Limbic-Predominant Phenotype.

OBJECTIVE: Late-onset amnestic mild cognitive impairment (aMCI) with long disease course and slow progression has been recently recognized as a possible phenotypical expression of a limbic-predominant neurodegenerative disorder. Basic emotion recognition ability crucially depending on temporo-limbic integrity is supposed to be impaired in this group of MCI subjects presenting a selective vulnerability of medio-temporal and limbic regions. However, no study specifically investigated this issue. METHODS: Hereby, we enrolled 30 aMCI with a biomarker-based diagnosis of Alzheimer's disease (i.e., aMCI-AD, n = 16) or a biomarker evidence of selective medio-temporal and limbic degeneration (aMCI-mTLD, n = 14). Ekman-60 Faces Test (Ek-60F) was administered to each subject, comparing the performance with that of 20 healthy controls (HCs). RESULTS: aMCI-mTLD subjects showed significantly lower Ek-60F global scores compared to HC (p = 0.001), whose performance was comparable to aMCI-AD. Fear (p = 0.02), surprise (p = 0.005), and anger (p = 0.01) recognition deficits characterized the aMCI-mTLD performance. Fear recognition scores were significantly lower in aMCI-mTLD compared to aMCI-AD (p = 0.04), while no differences were found in other emotions. CONCLUSIONS: Impaired social cognition, suggested by defective performance in emotion recognition tasks, may be a useful cognitive marker to detect limbic-predominant aMCI subjects among the heterogeneous aMCI population.

Development and internal validation of a prognostic model for 15-year risk of Alzheimer dementia in primary care patients.

BACKGROUND: The exploitation of routinely collected clinical health information is warranted to optimize the case detection and diagnostic workout of Alzheimer's disease (AD). We aimed to derive an AD prediction score based on routinely collected primary care data. METHODS: We built a cohort selecting 199,978 primary care patients 60 + part of the Health Search Database between January 2002 and 2009, followed up until 2019 to detect incident AD cases. The cohort was randomly divided into a derivation and validation sub-cohort. To identify AD and non-AD cases, we applied a clinical algorithm that involved two clinicians. According to a nested case-control design, AD cases were matched with up to 10 controls based on age, sex, calendar period, and follow-up duration. Using the derivation sub-cohort, 32 potential AD predictors (sociodemographic, clinical, drug-related, etc.) were tested in a logistic regression and selected to build a prediction model. The predictive performance of this model was tested on the validation sub-cohort by mean of explained variation, calibration, and discrimination measurements. RESULTS: We identified 3223 AD cases. The presence of memory disorders, hallucinations, anxiety, and depression and the use of NSAIDs were associated with future AD. The combination of the predictors allowed the production of a predictive score that showed an explained variation (pseudo-R2) for AD occurrence of 13.4%, good calibration parameters, and an area under the curve of 0.73 (95% CI: 0.71-0.75). In accordance with this model, 7% of patients presented with a high-risk score for developing AD over 15 years. CONCLUSION: An automated risk score for AD based on routinely collected clinical data is a promising tool for the early case detection and timely management of patients by the general practitioners.

Dementia-friendly intervention for hospitalized older adults with cognitive impairments: results of the Italian Dementia-Friendly Hospital Trial (IDENTITÀ).

Objective: To evaluate whether a short training focused on improving dementia care practices of the hospital staff was able to counteract functional loss and to decrease negative outcomes at discharge among hospitalized older adults with cognitive impairment.Method: Sixty-eight hospitalized participants aged 65 and over with cognitive impairment were included in the study, allocated in the control group (n = 34) and intervention group (n = 34). The intervention consisted of a short training of the hospital staff aimed at improving the management of patients with cognitive impairment. Participants were evaluated within 48 h of hospital admission and at discharge using a battery of tests including Barthel Index, Mini-Mental State Examination, and Hospital Anxiety and Depression Scale.Results: The intervention group demonstrated shorter hospital length of stay and a maintenance of the functional status at discharge compared to the control group. We observed no differences in cognitive ability between the two groups, and a trend towards a decrease of anxious symptoms in the intervention group compared to the control group.Conclusion: The results suggest that an intervention, focused on improving dementia care practices in healthcare staff, has the potential to improve the outcomes for hospitalized older adults with cognitive impairment.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Evaluation of Discriminative Detection Abilities of Social Cognition Measures for the Diagnosis of the Behavioral Variant of Frontotemporal Dementia: a Systematic Review.

The use of social tasks in the neuropsychological assessment of the behavioral variant of frontotemporal dementia (bvFTD) is at present not required by diagnostic guidelines, despite extensive literature shows relevant social cognitive dysfunctions in such patients. In this systematic review, we explored the clinical maturity of social cognition measures in the diagnosis of bvFTD. Papers were selected according to the PRISMA guidelines by searching the PubMed and Medline databases. Only papers reporting indices of diagnostic accuracy and/or sensitivity/specificity in classifying bvFTD from controls or from other relevant diseases were considered. Quality of evidence was assessed through QUADAS-2. Among the 663 articles entered in the paper selection only 14 papers were eligible for the scope of the present review and showed an overall moderate-to-low quality. The major risk of bias was the lack of pathological confirmation. The evaluation of the accuracy of social cognition tasks in bvFTD detection compared to normal controls, as well as in the discrimination with Alzheimer's disease and psychiatric patients, is mainly focused on emotion recognition and theory of mind. However, the use of different cognitive measures, variable task formats and the limited normative data hamper study comparability. Although literature seems to suggest that emotion recognition and ToM tasks could be the best choice to ensure a high diagnostic accuracy in clinical settings, further comparative studies are required and no recommendation concerning the use of a specific social task in bvFTD diagnosis can be currently provided.

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

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

The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint.

Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.

Cortical correlates of behavioural change in amyotrophic lateral sclerosis.

BACKGROUND: Behavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD). METHODS: Behavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach's α was used to test the reliability of bvFTD-related FBI clustering in our cohort. RESULTS: Sixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort. CONCLUSIONS: In non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.

The left inferior frontal gyrus: A neural crossroads between abstract and concrete knowledge.

Evidence from both neuropsychology and neuroimaging suggests that different types of information are necessary for representing and processing concrete and abstract word meanings. Both abstract and concrete concepts, however, conjointly rely on perceptual, verbal and contextual knowledge, with abstract concepts characterized by low values of imageability (IMG) (low sensory-motor grounding) and low context availability (CA) (more difficult to contextualize). Imaging studies supporting differences between abstract and concrete concepts show a greater recruitment of the left inferior frontal gyrus (LIFG) for abstract concepts, which has been attributed either to the representation of abstract-specific semantic knowledge or to the request for more executive control than in the case of concrete concepts. We conducted an fMRI study on 27 participants, using a lexical decision task involving both abstract and concrete words, whose IMG and CA values were explicitly modelled in separate parametric analyses. The LIFG was significantly more activated for abstract than for concrete words, and a conjunction analysis showed a common activation for words with low IMG or low CA only in the LIFG, in the same area reported for abstract words. A regional template map of brain activations was then traced for words with low IMG or low CA, and BOLD regional time-series were extracted and correlated with the specific LIFG neural activity elicited for abstract words. The regions associated to low IMG, which were functionally correlated with LIFG, were mainly in the left hemisphere, while those associated with low CA were in the right hemisphere. Finally, in order to reveal which LIFG-related network increased its connectivity with decreases of IMG or CA, we conducted generalized psychophysiological interaction analyses. The connectivity strength values extracted from each region connected with the LIFG were correlated with specific LIFG neural activity for abstract words, and a regression analysis was conducted to highlight which areas recruited by low IMG or low CA predicted the greater activation of the IFG for abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be involved in semantic processing, was a significant predictor of LIFG activity differentiating abstract from concrete words. The results show that the abstract conceptual processing requires the interplay of multiple brain regions, necessary for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG can be thus identified as the neural crossroads between different types of information equally necessary for representing processing and differentiating abstract concepts from concrete ones.

Affective and cooperative social interactions modulate effective connectivity within and between the mirror and mentalizing systems.

Decoding the meaning of others' actions, a crucial step for social cognition, involves different neural mechanisms. While the "mirror" and "mentalizing" systems have been associated with, respectively, the processing of biological actions versus more abstract information, their respective contribution to intention understanding is debated. Processing social interactions seems to recruit both neural systems, with a different weight depending on cues emphasizing either shared action goals or shared mental states. We have previously shown that observing cooperative and affective social interactions elicits stronger activity in key nodes of, respectively, the mirror (left posterior superior temporal sulcus (pSTS), superior parietal cortex (SPL), and ventral/dorsal premotor cortex (vPMC/dPMC)) and mentalizing (ventromedial prefrontal cortex (vmPFC)) systems. To unveil their causal organization, we investigated the effective connectivity underlying the observation of human social interactions expressing increasing cooperativity (involving left pSTS, SPL, and vPMC) versus affectivity (vmPFC) via dynamic causal modeling in 36 healthy human subjects. We found strong evidence for a model including the pSTS and vPMC as input nodes for the observed interactions. The extrinsic connectivity of this model undergoes oppositely valenced modulations, with cooperativity promoting positive modulations of connectivity between pSTS and both SPL (forward) and vPMC (mainly backward), and affectivity promoting reciprocal positive modulations of connectivity between pSTS and vmPFC (mainly backward). Alongside fMRI data, such divergent effective connectivity suggests that different dimensions underlying the processing of social interactions recruit distinct, although strongly interconnected, neural pathways associated with, respectively, the bottom-up visuomotor processing of motor intentions, and the top-down attribution of affective/mental states.

Mediterranean Diet and Cognitive Status in Free-Living Elderly: A Cross-Sectional Study in Northern Italy.

OBJECTIVE: Few data are available on the Italian elderly population with regard to adherence to the Mediterranean diet (MD) and cognitive impairment. Our aim was to investigate adherence to the MD and its association with cognitive function in an Italian urban sample. METHODS: A cross-sectional study of 279 participants aged ≥ 65 years (80 men, 199 women) was carried out at a nutritional center. Adherence to the MD was evaluated using a 14-item questionnaire. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). RESULTS: The clinical and nutritional assessments performed revealed 30.1% to have a dietary pattern in accordance with the MD; 13.6% had suspected or mild cognitive impairment (MMSE score ≤ 23). The MD pattern was associated with a lower risk of cognitive impairment (odds ratio [OR] = 0.39; 95% confidence interval [CI], 0.15-0.99; p = 0.045), as was the consumption of wine (OR = 0.37; 95% CI, 0.16-0.84; p = 0.018) and nuts (OR = 0.30; 95% CI, 0.13-0.69, p = 0.005). No association was found with other food groups. CONCLUSION: A closer adherence to the MD was associated with a better cognitive status. Further cohort studies and randomized controlled trials are warranted.

Screening for Aphasia in NeuroDegeneration for the Diagnosis of Patients with Primary Progressive Aphasia: Clinical Validity and Psychometric Properties.

BACKGROUND: We evaluated the psychometric proprieties of the Screening for Aphasia in NeuroDegeneration (SAND) battery in Italian primary progressive aphasia (PPA) and movement disorder (MD) patients. METHODS: The sample included 30 consecutive PPA and 45 MD patients who completed the SAND battery together with a clinical interview and a neurological/neuropsychological examination and 130 healthy controls (HC). RESULTS: The SAND battery showed good internal consistency and good convergent and divergent validity. receiver operating characteristic analysis revealed an area under the curve of 0.978 for PPA versus HC and of 0.786 for PPA versus MD. A cutoff ≥3 gave a sensitivity of 0.933% and a specificity of 0.946% for discriminating PPA versus HC, whereas a cutoff ≥5 gave a sensitivity of 0.767% and a specificity of 0.667% for discriminating PPA versus MD. CONCLUSION: These results indicate that the SAND battery is an adequate, reliable, and valid diagnostic tool for PPA.