Are the criteria for PD-MCI diagnosis comprehensive? A Machine Learning study with modified criteria.

BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) includes deficits in different cognitive domains, and one domain to explore for neurocognitive impairment following the DSM-V is social cognition. However, this domain is not included in current criteria for PD-MCI diagnosis. Moreover, tests vary across studies. It is, therefore, crucial to optimize cognitive assessment in PD-MCI. We aimed to do so by using Machine Learning. METHODS: 275 PD patients were included. Four cognitive batteries were created: two Standard ones (Levels I and II), applying current criteria and "traditional" tests; two Alternative ones (Levels I and II), which incorporated a test of social cognition. These batteries were included in the Random Forest (RF) classifier. To assess RF performance, the AUC was considered, and the Variable Importance Index was estimated to understand the contribution of each test in PD-MCI classification. RESULTS: Standard Level I and II showed an AUC of 0.852 and 0.892, while Alternative Level I and II showed an AUC of 0.898 and of 0.906. Variable Importance Index revealed that TMT B-A, Ekman test, RAVLT-IR, MoCA, and Action Naming were tests that most contributed to PD-MCI classification. CONCLUSION: The Alternative level I assessment demonstrated a similar classification capacity to the Standard level II assessment. This finding suggests that in the cognitive assessment of PD patients, it is crucial to consider the most affected cognitive domains in this clinical population, including social cognition. Taken together, these results suggest to revise current criteria for the diagnosis of PD-MCI.

"Communicative competence assessment of the person with aphasia caregiver: Standardization of the ACCA-CHECKLIST".

Aphasia constitutes a very complex clinical entity that requires a "competent" caregiver to interact with the person with aphasia (PWA). The literature lacks a valid and reliable set of standardized tools which can offer objective and quantifiable data of a caregiver's communicative competence. The aim of the study was to develop, standardize and validate an evaluation tool suited to measur the caregivers' competence in communicating with family members affected by aphasic disorders. Forty-two patients with aphasia and their respective caregivers were enrolled in the study. Caregivers' communicative competence was assessed through a new evaluation tool called ACCA-cl. Aphasia severity and functional communication abilities of the PWA were also investigated. Our data showed encouraging results regarding the reliability and the validity of the ACCA-cl scale in detecting the caregiver's communicative competence, especially as far as verbal content was considered. This scale can also be used to assess the improvement achieved by the caregiver after a communication training. The analysis provides encouraging findings for verbal content scales of the ACCA-cl and its possible use in clinical settings as a quantitative tool for detecting changes induced by the educational method of the caregiver. The tool is currently available in Italian.

The Social and Cognitive Online Training (SCOT) project: A digital randomized controlled trial to promote socio-cognitive well-being in older adults.

OBJECTIVES: Effective prevention programs targeting risk factors for cognitive decline in the elderly are recommended given the progressive increase in the aging of the general population. The Social and Cognitive Online Training (SCOT) project is a randomized, controlled, parallel clinical trial designed to prevent the age-related decline in executive and social functions. METHODS: The study included 60 cognitively healthy older adults (age = 71.8±5.3, education = 12.3±3.7, MoCA = 25.1±2.4). Participants underwent a baseline clinical and neuropsychological assessment and were then assigned to either an experimental group (SCOT) or a non-specific cognitive training group (CON). Both 8-week digital interventions included two individual cognitive training sessions and one group meeting per week. Post-intervention assessment evaluated the efficacy of the training on specific outcome measures: the Tower of London for executive functioning, the Ekman-60 Faces test, and the Mini-Social cognition & Emotional Assessment battery for social cognition. A measure of loneliness was included as an exploratory outcome. RESULTS: Baseline demographic and neuropsychological characteristics were balanced between SCOT (n = 29) and CON (n = 28) groups. Pre-post-intervention analyses showed improvements in executive functioning and social cognition in both groups, without significant interaction effects. Exploratory post-hoc analyses stratifying the SCOT group by training performance showed significant post-training improvements in executive functioning, emotion recognition, and cognitive theory of mind for high-performing participants. DISCUSSION: Results provide preliminary evidence for the beneficial effects of SCOT training, particularly for those who performed best during the training. The SCOT training could represent a new intervention to promote socio-cognitive well-being in the context of active ageing and dementia prevention.

Neural Correlates of Semantic Interference and Phonological Facilitation in Picture Naming: A Systematic Review and Coordinate-Based Meta-analysis.

Semantic interference (SI) and phonological facilitation (PF) effects occur when multiple representations are co-activated simultaneously in complex naming paradigms, manipulating the context in which word production is set. Although the behavioral consequences of these psycholinguistic effects are well-known, the involved brain structures are still controversial. This paper aims to provide a systematic review and a coordinate-based meta-analysis of the available functional neuroimaging studies investigating SI and PF in picture naming paradigms. The included studies were fMRI experiments on healthy subjects, employing paradigms in which co-activations of representations were obtained by manipulating the naming context using semantically or phonologically related items. We examined the principal methodological aspects of the included studies, emphasizing the existing commonalities and discrepancies across single investigations. We then performed an exploratory coordinate-based meta-analysis of the reported activation peaks of neural response related to SI and PF. Our results consolidated previous findings regarding the involvement of the left inferior frontal gyrus and the left middle temporal gyrus in SI and brought out the role of bilateral inferior parietal regions in PF.

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.

Functional alterations in resting-state networks for Theory of Mind in Parkinson's disease.

In Parkinson's disease (PD), impairment of Theory of Mind (ToM) has recently attracted an increasing number of neuroscientific investigations. If and how functional connectivity of the ToM network is altered in PD is still an open question. First, we explored whether ToM network connectivity shows potential PD-specific functional alterations when compared to healthy controls (HC). Second, we tested the role of the duration of PD in the evolution of functional alterations in the ToM network. Between-group connectivity alterations were computed adopting resting-state functional magnetic resonance imaging (rs-fMRI) data of four groups: PD patients with short disease duration (PD-1, n = 72); PD patients with long disease duration (PD-2, n = 22); healthy controls for PD-1 (HC-1, n = 69); healthy controls for PD-2 (HC-2, n = 22). We explored connectivity differences in the ToM network within and between its three subnetworks: Affective, Cognitive and Core. PD-1 presented a global pattern of decreased functional connectivity within the ToM network, compared to HC-1. The alterations mainly involved the Cognitive and Affective ToM subnetworks and their reciprocal connections. PD-2-those with longer disease duration-showed an increased connectivity spanning the entire ToM network, albeit less consistently in the Core ToM network, compared to both the PD-1 and the HC-2 groups. Functional connectivity within the ToM network is altered in PD. The alterations follow a graded pattern, with decreased connectivity at short disease duration, which broadens to a generalized increase with longer disease duration. The alterations involve both the Cognitive and Affective subnetworks of ToM.

Verbal and non-verbal recognition memory assessment: validation of a computerized version of the Recognition Memory Test.

BACKGROUND: The use of computerized devices for neuropsychological assessment (CNADs) as an effective alternative to the traditional pencil-and-paper modality has recently increased exponentially, both in clinical practice and research, especially due to the pandemic. However, several authors underline that the computerized modality requires the same psychometric validity as "in-presence" tests. The current study aimed at building and validating a computerized version of the verbal and non-verbal recognition memory test (RMT) for words, unknown faces and buildings. METHODS: Seventy-two healthy Italian participants, with medium-high education and ability to proficiently use computerized systems, were enrolled. The sample was subdivided into six groups, one for each age decade. Twelve neurological patients with mixed aetiology, age and educational level were also recruited. Both the computerized and the paper-and-pencil versions of the RMT were administered in two separate sessions. RESULTS: In healthy participants, the computerized and the paper-and-pencil versions of the RMT showed statistical equivalence for words, unknown faces and buildings. In the neurological patients, no statistical difference was found between the performance at the two versions of the RMT. A moderate-to-good inter-rater reliability between the two versions was also found in both samples. Finally, the computerized version of the RMT was perceived as acceptable by both healthy participants and neurological patients at System Usability Scale (SUS). CONCLUSION: The computerized version of the RMT can be used as a reliable alternative to the traditional version.

Social perception in deaf individuals: A meta-analysis of neuroimaging studies.

Deaf individuals may report difficulties in social interactions. However, whether these difficulties depend on deafness affecting social brain circuits is controversial. Here, we report the first meta-analysis comparing brain activations of hearing and (prelingually) deaf individuals during social perception. Our findings showed that deafness does not impact on the functional mechanisms supporting social perception. Indeed, both deaf and hearing control participants recruited regions of the action observation network during performance of different social tasks employing visual stimuli, and including biological motion perception, face identification, action observation, viewing, identification and memory for signs and lip reading. Moreover, we found increased recruitment of the superior-middle temporal cortex in deaf individuals compared with hearing participants, suggesting a preserved and augmented function during social communication based on signs and lip movements. Overall, our meta-analysis suggests that social difficulties experienced by deaf individuals are unlikely to be associated with brain alterations but may rather depend on non-supportive environments.

Connectome-based fingerprint of motor impairment is stable along the course of Parkinson's disease.

Functional alterations in brain connectivity have previously been described in Parkinson's disease, but it is not clear whether individual differences in connectivity profiles might be also linked to severity of motor-symptom manifestation. Here we investigated the relevance of individual functional connectivity patterns measured with resting-state fMRI with respect to motor-symptom severity in Parkinson's disease, through a whole-brain, data-driven approach (connectome-based predictive modeling). Neuroimaging and clinical data of Parkinson's disease patients from the Parkinson's Progression Markers Initiative were derived at baseline (session 1, n = 81) and at follow-up (session 2, n = 53). Connectome-based predictive modeling protocol was implemented to predict levels of motor impairment from individual connectivity profiles. The resulting predictive model comprised a network mainly involving functional connections between regions located in the cerebellum, and in the motor and frontoparietal networks. The predictive power of the model was stable along disease progression, as the connectivity within the same network could predict levels of motor impairment, even at a later stage of the disease. Finally, connectivity profiles within this network could be identified at the individual level, suggesting the presence of individual fingerprints within resting-state fMRI connectivity associated with motor manifestations in Parkinson's disease.

The Role of Working Memory and Short-Term Memory in Sentence Comprehension: A Systematic Review and Meta-Analysis in Probable Alzheimer's Disease.

The role of either short-term memory (STM) or working memory (WM) in sentence comprehension is a matter of debate. Although it is commonly accepted that memory resources are necessary for sentence comprehension, there is no agreement regarding the nature of their role. The aim of this review is to investigate and synthesize assessment tools and correlation data between STM or WM and sentence comprehension in probable Alzheimer's disease (AD). To this aim, a systematic review and meta-analysis of the literature was conducted according to the PRISMA guidelines. PubMed, Web of Science, Scopus, PsycInfo, and LLBA databases were searched. Two independent authors selected peer-reviewed articles published in English and focused on the relationship between STM or WM and sentence comprehension in probable AD. A total of 11 case-control studies were included at the end of the selection process. Most studies adopted offline tasks to evaluate sentence comprehension, while a small number of authors applied online experimental tasks. The digit span forward and backward were the most employed standardized tests to evaluate phonological STM and WM, respectively. The meta-analysis results supported the association between performance on STM and WM and comprehension tasks. However, moderate heterogeneity was found, mainly due to the small number of included studies, especially for STM, and the substantial variability of the adopted tasks. Therefore, in order to clarify the specific source of language comprehension deficits, new and sophisticated experiments should be conducted using adequate material.

Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

Concrete and Abstract Concepts in Primary Progressive Aphasia and Alzheimer's Disease: A Scoping Review.

The concreteness effect (CE), namely a better performance with concrete compared to abstract concepts, is a constant feature in healthy people, and it usually increases in persons with aphasia (PWA). However, a reversal of the CE has been reported in patients affected by the semantic variant of Primary Progressive Aphasia (svPPA), a neurodegenerative disease characterized by anterior temporal lobe (ATL) atrophy. The present scoping review aims at identifying the extent of evidence regarding the abstract/concrete contrast in Alzheimer's disease (AD) and svPPA and associated brain atrophy. Five online databases were searched up to January 2023 to identify papers where both concrete and abstract concepts were investigated. Thirty-one papers were selected and showed that while in patients with AD, concrete words were better processes than abstract ones, in most svPPA patients, there was a reversal of the CE, with five studies correlating the size of this effect with ATL atrophy. Furthermore, the reversal of CE was associated with category-specific impairments (living things) and with a selective deficit of social words. Future work is needed to disentangle the role of specific portions of the ATL in concept representation.

The Right Temporal Lobe and the Enhancement of Voice Recognition in Congenitally Blind Subjects.

BACKGROUND: Experimental investigations and clinical observations have shown that not only faces but also voices are predominantly processed by the right hemisphere. Moreover, right brain-damaged patients show more difficulties with voice than with face recognition. Finally, healthy subjects undergoing right temporal anodal stimulation improve their voice but not their face recognition. This asymmetry between face and voice recognition in the right hemisphere could be due to the greater complexity of voice processing. METHODS: To further investigate this issue, we tested voice and name recognition in twelve congenitally blind people. RESULTS: The results showed a complete overlap between the components of voice recognition impaired in patients with right temporal damage and those improved in congenitally blind people. Congenitally blind subjects, indeed, scored significantly better than control sighted individuals in voice discrimination and produced fewer false alarms on familiarity judgement of famous voices, corresponding to tests selectively impaired in patients with right temporal lesions. CONCLUSIONS: We suggest that task difficulty is a factor that impacts on the degree of its lateralization.

The FACE test: a new neuropsychological task to assess the recognition of complex mental states from faces.

BACKGROUND: Social cognition deficits are reported in several neurodegenerative diseases, including Parkinson's disease (PD). However, the availability of tasks for the clinical assessment is still limited, preventing the full characterization of socio-cognitive dysfunctions in neurological patients. This study aims to present a new task to assess the recognition of complex mental states from faces (FACE test), reporting normative data for the Italian population and an example of its clinical application to 40 PD patients. METHODS: Two-hundred twenty-nine Italian participants with at least 5 years of education were enrolled. Data were analyzed according to the method of equivalent scores; test-retest reliability and convergent validity were assessed. Two short versions of the FACE test were defined for clinical and research purposes. The prevalence of deficits in the FACE test was computed in the PD sample, as well as correlations with cognitive performance and diagnostic accuracy. RESULTS: Regression analyses revealed significant effects of demographic variables on FACE performance, with younger and more educated individuals showing higher scores. Twenty-eight percent of PD patients showed borderline/pathological performance, which was correlated with emotion recognition/attribution abilities, and attentive-executive functions. The FACE test was accurate (80%) in distinguishing PD patients with socio-cognitive dysfunctions from both controls and PD patients without emotion recognition/attribution difficulties. CONCLUSION: The FACE test represents a new tool assessing the ability to recognize complex mental states from facial expressions. Overall, these results support its use in both clinical and research settings, as well as the presence of affective processing deficits in a subsample of PD patients.

The role of verbal short-term memory in complex sentence comprehension: An observational study on aphasia.

BACKGROUND: The comprehension profile of people with agrammatism is a debated topic. Syntactic complexity and cognitive resources, in particular phonological short-term memory (pSTM), are considered as crucial components by different interpretative accounts. AIM: To investigate the interaction of syntactic complexity and of pSTM in sentence comprehension in a group of persons with aphasia with and without agrammatism. METHODS & PROCEDURES: A cohort of 30 participants presenting with aphasia was assessed for syntactic comprehension and for pSTM. A total of 15 presented with agrammatism and 15 had fluent aphasia. OUTCOMES & RESULTS: Linear nested mixed-model analyses revealed a significant interaction between sentence type and pSTM. In particular, participants with lower pSTM scores showed a reduced comprehension of centre-embedded object relatives and long coordinated sentences. Moreover, a significant interaction was found between sentence type and agrammatism, with a lower performance for passives within the agrammatic group. CONCLUSIONS & IMPLICATIONS: These results confirm that pSTM is involved in the comprehension of complex structures with an important computational load, in particular coordinated sentences, and long-distance filler gap dependencies. On the contrary, the specific deficit of the agrammatic group with passives is a pure syntactic deficit, with no involvement of pSTM.

Which components of famous people recognition are lateralized? A study of face, voice and name recognition disorders in patients with neoplastic or degenerative damage of the right or left anterior temporal lobes.

We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At the familiarity level, we found, as expected, a dissociation between a greater impairment of patients with right ATL lesions on the non-verbal (face and voice) recognition modalities and of those with left ATL lesions on name familiarity. Equally expected were results obtained at the naming level, because the worse naming scores for faces and voices were observed in left-sided patients. Less foregone were, for two reasons, results obtained at the semantic level. First, no difference was found between the two hemispheric groups when scores obtained on the verbal (name) and non-verbal (face and voice) recognition modalities were account for. Second, the face and voice recognition modalities showed a different degree of right lateralization. All groups of patients showed, indeed, both at the familiarity and at the semantic level, a greater difficulty in the recognition of voices regarding faces, but this difference reached significance only in patients with right ATL lesions, suggesting a greater right lateralization of the more complex task of voice recognition. A model aiming to explain the greater right lateralization of the more perceptually demanding voice modality of person recognition is proposed.

Deep Brain Stimulation in Parkinson Disease: A Meta-analysis of the Long-term Neuropsychological Outcomes.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidum internus (GPi) improves motor functions in patients with Parkinson's disease (PD) but may cause a decline in specific cognitive domains. The aim of this systematic review and meta-analysis was to assess the long-term (1-3 years) effects of STN or GPi DBS on four cognitive functions: (i) memory (delayed recall, working memory, immediate recall), (ii) executive functions including inhibition control (Color-Word Stroop test) and flexibility (phonemic verbal fluency), (iii) language (semantic verbal fluency), and (iv) mood (anxiety and depression). Medline and Web of Science were searched, and studies published before July 2021 investigating long-term changes in PD patients following DBS were included. Random-effects model meta-analyses were performed using the R software to estimate the standardized mean difference (SMD) computed as Hedges' g with 95% CI. 2522 publications were identified, 48 of which satisfied the inclusion criteria. Fourteen meta-analyses were performed including 2039 adults with a clinical diagnosis of PD undergoing DBS surgery and 271 PD controls. Our findings add new information to the existing literature by demonstrating that, at a long follow-up interval (1-3 years), both positive effects, such as a mild improvement in anxiety and depression (STN, Hedges' g = 0,34, p = 0,02), and negative effects, such as a decrease of long-term memory (Hedges' g = -0,40, p = 0,02), verbal fluency such as phonemic fluency (Hedges' g = -0,56, p < 0,0001), and specific subdomains of executive functions such as Color-Word Stroop test (Hedges' g = -0,45, p = 0,003) were observed. The level of evidence as qualified with GRADE varied from low for the pre- verses post-analysis to medium when compared to a control group.

Cognitive reserve and emotion recognition in the context of normal aging.

The Cognitive Reserve (CR) hypothesis accounts for individual differences in vulnerability to age- or pathological-related brain changes. It suggests lifetime influences (e.g., education) increase the effectiveness of cognitive processing in later life. While evidence suggests CR proxies predict cognitive performance in older age, it is less clear whether CR proxies attenuate age-related decline on social cognitive tasks. This study investigated the effect of CR proxies on unimodal and cross-modal emotion identification. Sixty-six older adults aged 60-78 years were assessed on CR proxies (Cognitive Reserve Index Questionnaire, NART), unimodal(faces only, voices only), and cross-modal (faces and voices combined) emotion recognition and executive function (Stroop Test). No CR proxy predicted performance on emotion recognition. However, NART IQ predicted performance on the Stroop test; higher NART IQ was associated with better performance. The current study suggests CR proxies do not predict performance on social cognition tests but do predict performance on cognitive tasks.