Background: Inflammasomes regulate the activation of caspases resulting in inflammation; inflammasome activation is dysregulated in Alzheimer’s disease (AD) and plays a role in the pathogenesis of this condition. Glibenclamide, an anti-inflammatory drug, could be an interesting way to down-modulate neuroinflammation. Methods: In this pilot study we verified with ex vivo experiments whether a glibenclamide-loaded nanovector (GNV) could reduce the NLRP3-inflammasome cascade in cells of AD patients. Monocytes isolated from healthy controls (HC) and AD patients were cultured in medium, alone or stimulated with LPS + nigericin in presence/absence of GNV. ASC-speck positive cells and inflammasome-related genes, proteins, and miRNAs expressions were measured. The polymorphisms of ApoE (Apolipoprotein E), specifically rs7412 and rs429358, as well as those of NLRP3, namely rs35829419, rs10733113, and rs4925663, were also investigated. Results: Results showed that ASC-speck+ cells and Caspase-1, IL-1β, and IL-18 production was significantly reduced (p < 0.005 in all cases) by GNV in LPS + nigericin-stimulated cells of both AD and HC. Notably, the NLRP3 rs10733113 AG genotype was associated with excessive inflammasome-related gene and protein expression. GNV significantly down-regulates inflammasome activation in primary monocytes, at least at protein levels, and its efficacy seems to partially depend on the presence of the NLRP3 rs10733113 genotype. Conclusions: All together, these results showed that GNV is able to dampen inflammation and NLRP-3 inflammasome activation in an ex vivo monocyte model, suggesting a possible role for GNV in controlling AD-associated neuroinflammation.

Technologies for frail elderly individuals facilitate the integration of care services, support the post-discharge period, and enhance independence and quality of life while reducing isolation. However, the lack of methodological rigor in studies on technologies for diagnosing and treating geriatric syndromes limits applied research. This study aimed to develop and validate a checklist considering technical readiness, clinical needs, and context to support the use of technologies primary in clinical practice and also in research settings. To this aim, a Delphi procedure was conducted in four rounds, followed by a pilot test assessing the checklist’s practical effectiveness. Twenty-nine items were defined and discussed. Among them, no item was deleted, while a total of eight items were reformulated. At the end of the assessment steps, 73% of items showed a high median relevance rating. The pilot test showed the difficulty in finding relevant information to complete the checklist as the only critical issue. This tool represents the first validated checklist in the field of technology-based healthcare for elderly individuals and supports the application of technologies in the diagnosis and treatment of geriatric syndromes by clinicians and researchers.

Post-traumatic amnesia (PTA), recently conceptualized as part of the broader syndrome known as post-traumatic confusional state (PTCS), marks a critical phase of recovery following moderate-to-severe traumatic brain injury (TBI). Indeed, this state is characterized not only by anterograde memory impairment but also by disorientation, agitation, and attention deficits. Given the phenotypic overlap between PTA/PTCS and delirium—both marked by fluctuating cognitive and attentional disturbances—EEG represents a promising tool for elucidating shared pathophysiological mechanisms. While delirium is typically associated with diffuse EEG slowing and the presence of slow-wave activity (SWA), thought to reflect underlying global cortical disruption, it remains unclear whether PTCS exhibits similar EEG underpinnings. In this prospective longitudinal study, we assessed dynamic EEG correlates of PTCS using the Grand Total EEG (GTE) score. We enrolled 42 consecutive TBI patients, classifying them at baseline into PTA/PTCS or emerged from PTA/PTCS, based on validated clinical assessments. Patients with PTA/PTCS exhibited significantly higher baseline GTE scores compared to TBI controls, reflecting severe EEG abnormalities characterized by diffuse slowing and disrupted rhythmic activity. Longitudinal follow-up revealed significant EEG improvements paralleling clinical recovery, confirming EEG’s sensitivity to dynamic clinical changes. Furthermore, the severity of EEG abnormalities significantly correlated with the duration of PTA/PTCS, underscoring EEG’s potential as an objective biomarker for monitoring recovery trajectories. Notably, these findings were independent of pharmacological confounders, as medication regimens were not significantly different across groups and timepoints. Our results support a reconceptualization of PTA/PTCS as a functional encephalopathy, analogous to delirium, with EEG slowing reflecting widespread yet reversible cortical dysfunction. By capturing these transient yet clinically critical changes, clinical EEG— quantified via GTE scores—offers a novel tool for diagnosing PTA/PTCS, stratifying its severity, and objectively monitoring its evolution in acute and subacute rehabilitation settings.

Background/Objectives: Cognitive impairment is highly prevalent among hospitalised adults but often remains under-recognised, particularly in non-neurological rehabilitation settings where clinical attention is mainly focused on physical recovery. Undetected cognitive impairment may adversely affect rehabilitation outcomes, functional recovery, and long-term care planning. Methods: A multicentre, prospective, longitudinal study, with a single-group assignment and a diagnostic purpose, will be conducted across three rehabilitation centres of the Don Carlo Gnocchi Foundation (Italy), enrolling 384 patients aged ≥45 years without severe psychiatric or neurological disorders, other than cognitive impairment, admitted to cardiac, pulmonary, orthopaedic rehabilitation, or intermediate care units for non-neurological conditions. At baseline (T0), all participants will undergo standardised clinical and cognitive screening. Individuals with suspected cognitive impairment, operationally defined as an Equivalent Score (ES) of 1 on the Montreal Cognitive Assessment–MoCA total score and/or an ES of 0 or 1 on at least one MoCA cognitive domain, including the Memory Index Score (MIS), and a random sample of those without, will undergo a comprehensive neuropsychological assessment. Participants with neuropsychologically defined cognitive impairment, based on objective deficits in the comprehensive neuropsychological assessment, will undergo plasma biomarker testing (GFAP, NfL, pTau-217), APOE genotyping, and brain CT. Participants with a MoCA total ES of 0 will be classified as having cognitive impairment on the basis of screening alone. At two prespecified sites, consecutive consenting participants with neuropsychologically defined cognitive impairment will additionally undergo an EEG vigilance protocol, auditory P300 recording, seven-day actigraphy, and overnight polysomnography. Patients with neuropsychologically defined cognitive impairment at T0 will undergo a 12-month follow-up assessment (T1) of the progression of cognitive impairment and plasma biomarkers; those enrolled in the neurophysiological substudy will additionally repeat the EEG vigilance protocol. Expected Results: The study will provide a conservative (lower-bound) estimate of the prevalence of documented and non-documented cognitive impairment, together with an estimate corrected for partial verification bias, in non-neurological rehabilitation settings. It will further characterise the cognitive profiles and examine their correlations with biomarkers of neurodegeneration (GFAP, NfL, pTau-217), APOE genotype, relative EEG spectral power and sleep intrusion measures, P300 latency and amplitude, actigraphy-derived Sleep Efficiency, and polysomnography-derived sleep stage proportions. Longitudinal data will enable the evaluation of cognitive trajectories and their biological correlates. Conclusions: The COGinREHAB study addresses a critical gap in rehabilitation medicine by implementing a structured, multimodal approach to the identification and characterisation of cognitive impairment in patients with non-neurological conditions. Its findings may facilitate earlier detection of cognitive impairment and inform the development of personalised rehabilitation and care pathways. Trial registration: ClinicalTrials.gov, NCT07731334.