University of Genoa

Introduction: Infections significantly impact morbidity and mortality in lung transplant (LuTx) recipients. This survey focused on documenting current practices regarding the prevention and management of infections in LuTx in Italy. Methods: A 52-question survey was administered online in the period from December 1, 2023, to January 31, 2024, assessing center characteristics, Tx team organization, microbiological investigations, infection prevention, and management. All Italian LuTx centers were invited to participate. Results: Nine out of 10 Italian LuTx centers answered. Most centers (6/9, 67%) performed LuTx only on adults. Chronic infection or colonization by Mycobacterium abscessus and Burkholderia cenocepacia is considered a contraindication to LuTx in five and two centers, respectively. For cytomegalovirus D+/R- patients, prophylaxis is used in six centers (67%), with a variable duration from 3 to 12 months. Two centers also use IgG. Three centers (33%) use a pre-emptive strategy. Four centers (45%) screen for Human herpesvirus 8 infection. Regarding antibiotic prophylaxis, most centers (6/9, 67%) utilise a dual regimen of anti-pseudomonal penicillin plus glycopeptide. The two most common durations of antibiotic prophylaxis were 72 h and 7 days, each reported by two centers (22%). Targeted prophylaxis against fungal infections is employed by a minority of centers (4/9, 44%). Inhaled amphotericin B is the most common antifungal, used as targeted prophylaxis (2/4, 50%) and universal prophylaxis (2/5, 40%). Almost all centers (8/9, 89%) involve the Tx infectious diseases specialist in the recipient management since the pre-listing period. Conclusion: There is considerable heterogeneity in infection management among Italian LuTx centers. Establishing a shared platform for data collection and outcome evaluation is essential to improve infection management.

Purpose Immunoglobulin G4-related disease (IgG4-RD) is a complex systemic fibroinflammatory condition with different clinical manifestations affecting multiple organ systems. Despite its rarity, the disease presents diagnostic and therapeutic challenges due to its mimicry of malignancies and other immune-mediated disorders. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease is the current state of art to confirm the diagnosis of IgG4-RD even in the absence of histological analysis. However, this classification excludes atypical sites, focusing on the more typical ones, even in case of histological confirmation. In the ENT field, several localizations of this disease have been described. Methods We report two clinical cases at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa affected by IgG4-RD arising in atypical sides of the head and neck region. Additionally, we perform a clinical review of the current literature. Discussion The review provides an extensive overview of IgG4-RD, encompassing epidemiology, clinical manifestations, diagnostic approaches, and therapeutic strategies. We discuss the evolution of diagnostic criteria, emphasizing the necessity of interdisciplinary collaboration among clinicians, radiologists, and pathologists for accurate diagnosis. Diagnostic imaging plays a crucial role, with characteristic radiological patterns aiding in the identification of affected organs. However, definitive diagnosis often requires histopathological confirmation, highlighting the importance of biopsy in challenging cases. We also focus on the treatment of IgG4-RD which poses significant challenges, with glucocorticoids remaining the cornerstone of therapy. Emerging steroid-sparing agents such as rituximab and Dupilumab, show promising results in refractory or recurrent disease. Conclusions IgG4-RD is a multisystemic fibroinflammatory disease that can potentially affect any part of the body. The 2019 ACR/EULAR 3-stage classification criteria for IgG4-RD considers only a few head and neck sites. Therefore, it is of paramount importance that neurosurgeons, head and neck surgeons, and oral and maxillofacial pathologists are familiar with the clinicopathological manifestations of IgG4-RD in these sites to avoid misdiagnosis and inappropriate treatment, which can lead to a decrease in patients’ quality of life. To our knowledge, there are no risk factors or genetic predispositions. Further studies are needed to elucidate the pathophysiology of IgG4-RD with the aim of providing a targeted therapy that could spare steroid-related effects and reduce relapses.

Masonry arches play a crucial role in the seismic response of historic masonry buildings. Although masonry arches are often subjected to large support displacements that alter and deform their geometries over time, their response to seismic actions is generally analysed using idealized, perfect geometries. This paper aims to assess the effect of large support displacements on the response of masonry arches to lateral loads. To this end, a small-scale segmental dry-joint masonry arch subjected to the vertical displacement of one support was investigated. Using a rigid block modelling approach recently proposed in the literature, the arch was modelled as an assemblage of rigid voussoirs connected by no-tension frictional contact interfaces. The response of the arch to lateral loads, applied in one direction, and to vertical support displacements was assessed through nonlinear static analyses. To evaluate the effect of support displacements, lateral loads were applied to a series of deformed arch geometries resulting from the application of increasing values of the imposed vertical displacement. The results of the numerical analyses provided new insights into how support displacements affect the lateral load response of masonry arches, showing that they may significantly reduce both the horizontal action triggering collapse and the ultimate displacement capacity.

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restores light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.

Unreinforced masonry (URM) buildings are highly susceptible to cumulative damage, as demonstrated by the damage observations collected during and after numerous earthquake sequences. However, most previous numerical studies assessing cumulative damage in URM buildings have failed to fully capture the extent of the phenomenon observed in real events. This article aims to address this gap by applying a newly developed methodology for modeling the accumulation of damage in URM buildings in risk assessment case studies. This methodology quantifies the cumulative damage using an energy- and displacement-based damage index (DI) within a component-based framework. The methodology is validated using data from the URM school building in Visso that sustained severe, progressive damage during the 2016 Central Italy earthquake sequence. Additionally, this DI is employed to develop hazard-consistent, damage-state-dependent fragility curves for five case-study URM buildings through consecutive nonlinear dynamic analyses. The fragility analysis results align with real-world observations, indicating a significant reduction in structural capacity due to cumulative damage. These set of fragility curves are then utilized in a risk assessment exercise. The last part of this study compares the impact on risk estimates when incorporating damage accumulation and earthquake sequences using the proposed methodology versus the conventional approach, which assumes only independent mainshocks affecting buildings in their intact state. The results reveal that the conventional approach underestimates the average annual losses for these five URM buildings in Central Italy by 45%–85%. Although the level of underestimation may vary for other URM buildings in other regions, it is undeniable that the conventional approach consistently underestimates the risk for URM structures by a significant margin.

The gluteal region has become a rising area of interest in plastic surgery in recent years, as reflected in body contouring surgery trends. In this study, the authors explain what the arrow effect consists of and how to highlight it during a Brazilian butt lift or a gluteal liposculpture: liposuction of the sacral triangle, fat grafting of the upper gluteal quadrants, liposuction of the dimples of Venus and of the midline superficially to the spinal column, and fat grafting of the erector spinae muscles.

The blood-brain barrier (BBB) maintains brain homeostasis but also prevents most drugs from entering the brain. No paracellular diffusion of solutes is allowed because of tight junctions that are made impermeable by the expression of claudin5 (CLDN5) by brain endothelial cells. The possibility of regulating the BBB permeability in a transient and reversible fashion is in strong demand for the pharmacological treatment of brain diseases. Here, we designed and tested short BBB-active peptides, derived from the CLDN5 extracellular domains and the CLDN5-binding domain of Clostridium perfringens enterotoxin, using a robust workflow of structural modeling and in vitro validation techniques. Computational analysis at the atom level based on solubility and affinity to CLDN5 identified a CLDN5-derived peptide not reported previously called f1-C5C2, which was soluble in biological media, displayed efficient binding to CLDN5, and transiently increased BBB permeability. The peptidomimetic strategy described here may have potential applications in the pharmacological treatment of brain diseases.

Metaphor comprehension has been investigated in neurodevelopmental disorders, but studies devoted to adults with dyslexia are few and present inconsistent results. The present study sought to investigate how adults with dyslexia process novel metaphors. Individual differences in vocabulary, working memory, and Theory of Mind were also assessed. An online metaphor comprehension task based on the Visual World Paradigm was carried out with eye-tracking. Metaphors and corresponding literal sentences were aurally presented in isolation, and participants were asked to select a picture that best corresponded to the sentence they heard. Our results indicated that participants with dyslexia chose metaphor interpretations at a similar rate as did the control group. However, online processing data indicated generally slower response times, with a particular delay in processing metaphorical utterances. Eye movement analyses provided further insights into the underlying nature of the processing slowdowns, highlighting specific challenges encountered by individuals with dyslexia when interpreting figurative language.

Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hyper-sensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods , enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.

Background Dementia with Lewy bodies (DLB) is a an a‐synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB‐related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis. DLBRP has been identified in few different cohorts but lacks a multicentric validation. Methods FDG PET scans from 259 DLB patients and 176 normal controls (NC) were obtained from eight centres from European DLB Consortium (EDLB, 180 patients), Alzheimer’s disease Neuroimaging Initiative (ADNI, 135 NC) and local dataset from Ljubljana (LJU, 79 patients and 41 NC). FDG PET scans were pre‐processed and we used topographic profile rating to calculate the DLBRP expression (i.e. subject scores). Subject scores were compared between groups using t tests and ANOVA and correlated with clinical parameters using Pearson’s correlation coefficient. Results Patients from different centres differed in MMSE (p < 0.001), proportion of patients with parkinsonism (p < 0.001) and visual hallucinations (p < 0.001), but not in age (p = 0.15) or sex distribution (p = 0.13). DLB patients from all centres had significantly higher DLBRP expression than NCs (all p < 0.001). We could accurately distinguish between DLB and NC (AUC = 0.983) based on DLBRP expression. We observed a negative correlation between DLBRP expression and MMSE (r = –0.30, p < 0.001). The expression of DLBRP differed among centres, post hoc analysis showed that only patients from Barcelona had significantly lower DLBRP subject scores in comparison to other groups but they were also less cognitively impaired. Patients with visual hallucinations (p < 0.001) had significantly higher DLBRP expression than those without hallucinations and patients with abnormal Datscan™ (p = 0.02) had higher DLBRP expression than those with normal Datscan™. Other core features, levodopa or antidementives did not affect the DLBRP expression. Conclusions We showed that DLBRP can accurately distinguish between DLB and NC from multiple centres and different scanners. The DLBRP expression correlated with measurements of cognitive impairment. This validation study confirms that the DLBRP is a robust metabolic imaging biomarker of DLB.

Background Patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) are characterized by abnormalities in resting‐state electroencephalographic (rsEEG) rhythms as measures of brain neural synchronization dysfunction (Babiloni et al., PMID: 33860614). Here, we tested the two following hypotheses that those rsEEG abnormalities: (i) may be higher in ADMCI patients than in patients with MCI not due to AD (noADMCI); and (ii) may be related to the AD diagnostic amyloid‐tau biomarkers derived from cerebrospinal fluid (CSF). Method Datasets in 70 ADMCI patients, 45 patients noADMCI, and 45 normal elderly (Healthy) participants originated from a Eurasian archive. The eyes‐closed rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta and gamma bands. The eLORETA freeware estimated rsEEG cortical sources. Result Statistical results showed: (i) compared with the Healthy group, the posterior alpha rsEEG source activities were more reduced in the ADMCI group than in the noADMCI group (p < 0.001; Figure 1); (ii) in the ADMCI group, a strong negative correlation between the CSF phospho‐tau levels and the occipital alpha rsEEG source activities was observed (r = 0.4, p < 0.001; Figure 2). Interestingly, in the ADMCI group, no correlation between the CSF and magnetic resonance imaging (MRI; neurodegeneration) variables was observed. Conclusion In ADMCI patients, the abnormalities of cortical neural synchronization mechanisms underpinning brain arousal and vigilance are related to the AD diagnostic phospho‐tau biomarkers and precede a similar relationship between AD amyloid‐tau and neurodegeneration biomarkers. Remarkably, the amyloid‐tau‐neurodegeneration (ATN) AD model may be enriched with those pathophysiological ‘P’ biomarkers as revealed by rsEEG rhythms.

Background Vigilance and sleep disturbances in Alzheimer’s and related diseases, even at the stage of mild cognitive impairment (MCI), have been extensively documented, showing abnormal daytime naps and alterations in the sleep‐wake cycle. However, the EEG correlates of the transition from wakefulness to light sleep have not yet been compared between MCI patients due to Alzheimer’s vs. other neurodegenerative diseases. Therefore, it is unclear whether there are specific features of these correlates in Alzheimer’s disease (AD) patients. This issue was investigated in the present study for the first time. Method Data were analyzed from an international database (https://www.pdwaves.eu/) comprising neuropsychological tests, long resting‐state EEG recordings, cerebrospinal fluid biomarkers, and MRI. For this study, 18 ADMCI patients, 9 NOADMCI patients, and 11 age‐ and sex‐matched healthy (Nold) participants showing transitions from wakefulness to light sleep during the EEG recording were selected based on the evaluation of two researchers blinded to the diagnoses. EEG periods were classified into four classes according to Hori et al.’s criteria: eyes open, eyes closed, EEG flattening, and EEG ripples (the last two representing drowsiness/light sleep stages). Individual alpha frequency peak (IAF) was obtained and used to determine EEG delta, theta, and alpha (1, 2, and 3) bands. Regional EEG cortical sources (Frontal, Parietal, and Occipital) were estimated using eLORETA freeware and the ratio of the source current density for the eyes closed and ripples conditions (EC/R) was considered as the EEG correlate of sleep‐wake transitions. Result Participants’ characteristics are reported in Table 1. The ANOVA showed a 2‐way interaction between Group and Band (p<.001), unveiling reduced EC/R source activity in the alpha 2 (p‐values<.001) and alpha 3 (p‐values<.001) bands in the ADMCI and NOADMCI groups (Figure 1). No differences in EEG source activity were found between the ADMCI and NOADMCI groups (p>.05). Conclusion The preliminary results of the present study showed widespread abnormalities in the cortical neurophysiological mechanisms oscillating at alpha frequencies in patients with Alzheimer’s and related diseases at the stage of MCI, but no differences between Alzheimer’s and non‐Alzheimer’s diseases. Future studies should cross‐validate these findings with larger clinical populations and test their relationship with night sleep disorders.

Background Several clinical guidelines and recommendations have been developed to improve the diagnostic process of patients with dementia, with the aim of optimising patient care and fostering a cost‐effective use of resources. However, patient characteristics and organizational factors in clinical practice can lead physicians to deviate from recommendations. In this context, process mining (PM) is a powerful technique for evaluating the compliance of actual to ideal diagnostic pathways, but has never been used in the cognitive field. This study aims to pilot the use of PM to study the diagnostic workup of patients with cognitive complains in an academic memory clinic. Method We retrospectively reviewed medical charts of 539 consecutive new patients referred to the University Hospitals of Geneva (Switzerland) between July 2021 and December 2022. The collected information includes socio‐demographic data, number and dates of clinical visits and biomarker exams (e.g., FDG‐, amyloid‐, tau‐PET, cerebrospinal fluid ‐ CSF). The pMineR package, a R library for PM, was used for data inspection and process discovery (e.g., First Order Markov Model ‐ FOMM, Careflow Miner ‐ CFM) to extract features of most frequent diagnostic pathway according to clinical stage. Result Patients were 96 subjective cognitive decline (SCD; MMSE: 28.5±1.6), 308 Mild Cognitive Impairment (MCI; MMSE: 26.5±2.7), and 135 Mild Dementia (DEM; MMSE: 22.7±3.2). FOMM showed that all SCD patients received a syndromic diagnosis based on a detailed neuropsychological evaluation and a morphological imaging. CSF was the first‐line biomarker to ascertain the aetiology of cognitive impairment, used in 90 MCI (30%) and 32 DEM (24%). A second‐line biomarker (e.g., amyloid‐, FDG‐, Tau‐PET) was required in 23% of MCI and 16% of DEM. Differential PM with CFM revealed that DEM was more commonly referred to the first clinical assessment with morphological imaging than MCI (DEM:68/135vs.MCI:123/308, ratio:1.8; p = 0.047). Conclusion These preliminary results demonstrate that the PM approach is appropriate for describing the diagnostic workup in memory clinics. Using the same approach and study design, a further project will evaluate the diagnostic pathways in 6 European academic memory clinics and contrast them to recommendations recently issued from a large European consensus effort (Frisoni, LancetNeurol 2024).

Background In 2020, five Italian scientific societies issued diagnostic recommendations to improve the rational and combined use of biomarkers in the clinical practice of Italian memory clinics (Boccardi et al., 2020). The present project will aim to compare the most frequent diagnostic workups in three academic memory clinics before (pre‐recommendations: January 2018 ‐ December 2019) and after (post‐recommendations: October 2022 ‐ October 2023) the release of the recommendations to assess their implementation in clinical routine. Preliminary results on pre‐recommendations data are presented here. Method We retrospectively reviewed the medical charts of consecutive patients referred to the academic memory clinics of Padova, Chieti, and Roma for a first visit in the pre‐recommendations period. The collected information included socio‐demographic data, number and dates of clinical visits and biomarker exams (i.e., FDG‐, amyloid‐, tau‐PET, cerebrospinal fluid [CSF], DAT SPECT/PET, and cardiac MIBG scintigraphy). A diagnostic hypothesis was extracted for each clinical visit until the final diagnosis. Result Since October 2022, 500 patients’ medical charts were reviewed. Patients were divided into three groups: 148 (30%) patients came to clinical observation not for diagnostic purposes (e.g., second opinion, disability claim), 242 (48%) received a diagnosis based on neuropsychological assessment and morphological imaging only, and 110 (22%) were in a biomarker‐based diagnostic pathway. The latter group included 31 patients with Alzheimer’s disease (AD), 19 with frontotemporal lobar degeneration (FTLD), 28 with a Lewy body spectrum disease (LBD), and 32 with non‐neurodegenerative aetiology or vascular dementia. Biomarker‐based diagnoses of AD, FTLD and non‐neurodegenerative diseases were commonly based on FDG‐PET (AD: 77%, FTLD: 84%, non‐neurodegenerative: 66%) and CSF (52%, 37%, and 44%). In LBD (n = 28), the first‐choice biomarker was FDG‐PET (61%), followed by DAT SPECT/PET (39%). Conclusion This preliminary analysis outlines the most frequent diagnostic pathways, providing the prevalence of the use of biomarkers in Italian academic memory clinics in the pre‐recommendations period. Once the post‐recommendations data collection is completed, we will evaluate whether the recommendations are feasible and usable in real‐world clinical workups by applying process‐mining techniques (Gatta et al., 2020) to estimate the prevalence and type of deviations from the ideal pathway based on recommendations.

Background Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients. Since hypometabolism presumably precedes overt brain atrophy, we additionally investigate the association between regional gene expression and hypometabolism in DLB. Method To investigate the association between gene expression and regional volumes, 165 DLB patients along with 165 age‐ and sex‐matched healthy controls from three European centres and the Mayo Clinic (USA) were included. Regional volumes were quantified from MRI using SPM12 in 112 cortical, subcortical, and cerebellar brain regions, and compared between groups, using w‐scores. Regional expression data of seven genes involved in the formation and degradation of pathological protein aggregates (APOE, APP, BIN1, GBA, MAPT, SNCA, TMEM175) was extracted from six healthy donors from the Allen Human Brain Atlas and correlated with regional volumetric w‐scores. To assess the predictive value of regional gene expression on regional volumes we used Gaussian stepwise backwards linear regression including all seven genes as predictors. To investigate the association between gene expression and hypometabolism, we are currently applying the same analysis pipeline to FDG‐PET data of 139 DLB patients from 8 European centres. Result Most brain regions showed lower volumes in DLB patients compared to healthy controls, with differences being most pronounced in occipital and parietal lobes. Regional expression of APOE correlated positively with regional volumes in DLB. Conversely, regional expression of MAPT correlated negatively with regional volumes. Both APOE and MAPT gene expression were significant predictors of regional volumes in the regression analysis. None of the other gene expression values was significantly associated with regional volumes in DLB. Conclusion Our findings show that regional expression of genes associated with the abnormal accumulation of amyloid and tau, common co‐pathologies in DLB, partially account for the brain atrophy pattern observed in DLB patients. Analyses are ongoing for the hypometabolism pattern. Our finding emphasises the relevance of co‐pathologies in predicting atrophy progression and identifying potential targets for future disease‐modifying treatments.

Background Alzheimer's disease (AD) is the most common form of dementia, predominantly manifesting as amnestic impairment. However, atypical presentations such as logopenic variant of primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS) and frontal AD pose diagnostic challenges. This study presents preliminary data from a retrospective analysis investigating brain functional differences between typical and atypical AD forms. Specifically, a structural connectome, a comprehensive map of anatomical white matter connections in the brain, was employed alongside late‐phase amyloid [¹⁸F]FBB PET, which resembles focal regional amyloid uptake. Additionally, the research aims to examine whether early‐phase amyloid [¹⁸F]FBB PET can serve as a surrogate for glucose metabolism throughout various brain regions, similar to [¹⁸F]FDG PET. Method Thirty patients have been recruited, including 13 with atypical AD (median age 70; median MMSE 21) and 17 with typical amnestic phenotype (median age 71; median MMSE 23). Neuropsychological tests, 3D isotropic T1 MRI, [¹⁸F]FDG PET, and [¹⁸F]FBB PET (consisting of 3 early frames and 1 late frame) were performed for each subject. Structural and functional images underwent spatial registration, segmentation, and intensity normalization, using a custom Python pipeline based on FreeSurfer and ANTs tools. Basic statistics were employed to establish functional patterns and assess their statistical significance. Structural connectomes derived from probabilistic tractography on DWI images of 30 healthy subjects were employed. Result Results revealed a significant preservation of the hippocampus in atypical AD phenotypes (p<0.05). The connectome analysis demonstrated variations in interconnections among late‐phase amyloid PET uptake regions, distinguishing between atypical and typical AD forms. Additionally, there is support for the hypothesis that early‐phase amyloid PET serves as a reliable marker for synaptic dysfunction. Conclusion In conclusion, these preliminary findings suggest that structural connectomes in PET imaging can unveil unique neurodegenerative pathways in atypical AD patients. Moreover, the study supports the notion that early amyloid PET phases can provide insights into neurodegeneration among patients with atypical AD, akin to [¹⁸F]FDG PET.

Background The amplitude of resting‐state electroencephalographic (rsEEG) rhythms is a promising neurophysiological biomarker to investigate the abnormalities of oscillatory neurophysiological thalamocortical mechanisms related to the general cortical arousal and vigilance in wakefulness in patients with dementia due to neurodegenerative diseases as Alzheimer’s disease (ADD), Parkinson’s disease (PDD) and Lewy Body disease (DLB). Here, we tested the hypothesis that the reactivity of posterior rsEEG alpha (about 8‐12 Hz) rhythms during the transition from eyes‐closed to ‐open condition may be lower in PDD patients than in DLB patients. Methods A Eurasian database provided clinical‐demographic‐rsEEG datasets in 35 ADD patients, 65 PDD patients, 30 DLB patients, and 25 matched cognitively unimpaired (Healthy) persons. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. The eLORETA freeware was used to estimate cortical rsEEG sources. Results Results showed substantial (i.e., greater than ‐10%) reduction (reactivity) in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 88% of the Healthy seniors, 53% of ADD patients, 53% of the DLB patients, and only 37% of the PDD patients (Figure 1). In these alpha‐reactive participants, there was lower reactivity in the posterior alpha source activities in the three neurodegenerative (i.e., ADD, PDD, and DLB) groups than in the Healthy group. Furthermore, the reduction of the occipital alpha reactivity was stronger in the PDD and DLB groups than in the ADD group. Finally, the reduction of the parietal alpha reactivity was stronger in the PDD group than in the ADD and DLB groups (Figure 2). Conclusion These results suggest that ADD, PDD, and DLB patients may be characterized by very poor reactivity in the posterior cortical mechanisms desynchronizing rsEEG alpha rhythms in relation to increased vigilance levels as an interesting neurophysiological biomarker. This biomarker may be used as a primary endpoint for interventions with drugs or brain electromagnetic stimulations to improve vigilance regulation and quality of life in neurodegenerative patients, allowing them to follow TV programs and interactions in their social environment.

Background Dementia with Lewy bodies (DLB) is a an α‐synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB‐related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis. DLBRP has been identified in few different cohorts but lacks a multicentric validation. Methods FDG PET scans from 259 DLB patients and 176 normal controls (NC) were obtained from eight centres from European DLB Consortium (EDLB, 180 patients), Alzheimer’s disease Neuroimaging Initiative (ADNI, 135 NC) and local dataset from Ljubljana (LJU, 79 patients and 41 NC). FDG PET scans were pre‐processed and we used topographic profile rating to calculate the DLBRP expression (i.e. subject scores). Subject scores were compared between groups using t tests and ANOVA and correlated with clinical parameters using Pearson’s correlation coefficient. Results Patients from different centres differed in MMSE (p < 0.001), proportion of patients with parkinsonism (p < 0.001) and visual hallucinations (p < 0.001), but not in age (p = 0.15) or sex distribution (p = 0.13). DLB patients from all centres had significantly higher DLBRP expression than NCs (all p < 0.001). We could accurately distinguish between DLB and NC (AUC = 0.983) based on DLBRP expression. We observed a negative correlation between DLBRP expression and MMSE (r = –0.30, p < 0.001). The expression of DLBRP differed among centres, post hoc analysis showed that only patients from Barcelona had significantly lower DLBRP subject scores in comparison to other groups but they were also less cognitively impaired. Patients with visual hallucinations (p < 0.001) had significantly higher DLBRP expression than those without hallucinations and patients with abnormal Datscan™ (p = 0.02) had higher DLBRP expression than those with normal Datscan™. Other core features, levodopa or antidementives did not affect the DLBRP expression. Conclusions We showed that DLBRP can accurately distinguish between DLB and NC from multiple centres and different scanners. The DLBRP expression correlated with measurements of cognitive impairment. This validation study confirms that the DLBRP is a robust metabolic imaging biomarker of DLB.