Search Results (560)

Background/Objectives: Dementia is a leading cause of cognitive decline, with significant challenges for early detection and timely intervention. The lack of effective, user-centred technologies further limits clinical response, particularly in underserved areas. This study aimed to develop and describe a co-design process for creating a Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-compliant, AI-powered Smart Assistant (SmartApp) to monitor neurocognitive decline, while ensuring accessibility, clinical relevance, and responsible AI integration. Methods: A co-design framework was applied using a novel combination of Agile principles and the Double Diamond Model (DDM). More than twenty iterative Scrum sprints were conducted, involving key stakeholders such as clinicians (psychiatrist, psychologist, physician), designers, students, and academic researchers. Prototype testing and design workshops were organised to gather structured feedback. Feedback was systematically incorporated into subsequent iterations to refine functionality, usability, and clinical applicability. Results: The iterative process resulted in a SmartApp that integrates a DSM-5-based screening tool with 24 items across key cognitive domains. Key features include longitudinal tracking of cognitive performance, comparative visual graphs, predictive analytics using a regression-based machine learning module, and adaptive user interfaces. Workshop participants reported high satisfaction with features such as simplified navigation, notification reminders, and clinician-focused reporting modules. Conclusions: The findings suggest that combining co-design methods with Agile/DDM frameworks provides an effective pathway for developing AI-powered clinical tools as per responsible AI standards. The SmartApp offers a clinically relevant, user-friendly platform for dementia screening and monitoring, with potential to support vulnerable populations through scalable, responsible digital health solutions. Full article

Background: The fetal period is critical for neurodevelopment, with maternal diet emerging as a key environmental factor influencing long-term child health. This study investigated the associations between maternal dietary patterns during pregnancy and neurocognitive and behavioral outcomes in 4-year-old children, with a particular focus on sex-related differences. Methods: We used data from the Piccolipiù Italian birth cohort, including 2006 mother/child pairs. Maternal dietary intake during pregnancy was assessed via a questionnaire and categorized into distinct patterns using Principal Component Analysis (PCA). Child neurodevelopment was evaluated at age 4 using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Child Behavior Checklist (CBCL 1.5–5). Linear and logistic regression models were employed, adjusting for potential confounders and stratifying by child sex. Results: Two major maternal dietary patterns were identified: “Processed and high-fat foods” and “Fresh foods and fish”. Higher maternal adherence to the “Processed and high-fat foods” pattern was associated with increased externalizing behaviors in offspring (β = 0.88; 95%CI 0.28–1.49; p = 0.004). In males, this pattern was associated with an increased clinical risk of Attention Deficit Hyperactivity Disorder (ADHD) (OR (Odds Ratio) = 1.13; 95%CI: 1.02–1.26; p = 0.021). Conclusions: Our findings indicate that maternal consumption of a diet rich in processed and high-fat foods during pregnancy is associated with increased behavioral problems in children, with sex-specific vulnerabilities: slightly higher externalizing behaviors in girls and an increased risk of ADHD in boys. These results underscore the importance of promoting healthy maternal dietary patterns during pregnancy as a targeted early prevention strategy for supporting child neurodevelopment. Full article

Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial dysfunction considered central to its associated comorbidities. Despite notable advances in OSA research, the biological mechanisms driving these complications remain insufficiently understood. The present study aimed to examine the associations between redox status, proinflammatory biomarkers, and the gene expression of full-length receptor for advanced glycation end products (flRAGE) and transforming growth factor beta 1 (TGF-β1) in relation to the presence and severity of OSA. Materials and Methods: The study cohort comprised 125 participants with diagnosed OSA and 42 controls without evidence of OSA. General and clinical characteristics were recorded for all participants. Laboratory analyses included the assessment of redox and inflammatory markers in serum and plasma, while flRAGE and TGF-β1 messenger ribonucleic acids (mRNA) were quantified in peripheral blood mononuclear cells. Results: Patients with OSA demonstrated elevated oxidative stress and inflammation, characterized by increased total antioxidant status (TAS) and C-reactive protein CRP levels, together with reduced concentrations of soluble RAGE (sRAGE). The severity of OSA, indicated by the apnea-hypopnea index, increases total oxidative status (TOS) and TGF-β1 mRNA, while sRAGE decreases. The sRAGE–ROS-related factor was negatively associated with OSA, whereas the redox status factor showed a positive association. TOS was independently and positively correlated with OSA severity. Conclusions: Individuals with OSA exhibit a state of enhanced oxidative stress and inflammation. Increasing severity of OSA was associated with rising TOS and TGF-β1 mRNA expression, accompanied by declining sRAGE concentrations. A combined redox–inflammatory biomarker profile was found to be associated with both the presence and severity of OSA. Full article

Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article

Glaucoma is traditionally classified as an ocular disease characterized by progressive retinal ganglion cell (RGC) loss and optic nerve damage. However, emerging evidence suggests that its pathophysiology may extend beyond the eye, involving trans-synaptic neurodegeneration along the visual pathway and structural changes within central brain regions, including the lateral geniculate nucleus and visual cortex. In this narrative review, we have used the phrase ‘brain involvement’ to underscore central changes that accompany or follow retinal ganglion cell loss; we have not intended to redefine glaucoma as a primary cerebral disorder. Neuroimaging studies and neurocognitive assessments in adult glaucoma patients, primarily older individuals with primary open-angle glaucoma reveal that glaucoma patients may exhibit alterations in brain connectivity and cortical thinning, aligning it more closely with neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This evolving neurocentric perspective raises important questions regarding shared mechanisms—such as mitochondrial dysfunction, chronic inflammation, and impaired axonal transport—that may link glaucomatous optic neuropathy to central nervous system (CNS) pathology. These insights open promising therapeutic avenues, including the repurposing of neuroprotective and neuroregenerative agents, targeting not only intraocular pressure (IOP) but also broader CNS pathways. Furthermore, neuroimaging biomarkers and brain-targeted interventions may play a future role in diagnosis, prognosis, and individualized treatment. This review synthesizes current evidence supporting glaucoma as a CNS disease, explores the mechanistic overlap with neurodegeneration, and discusses the potential clinical implications of glaucoma within a neuro-ophthalmologic paradigm. Full article

Background: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders. Methods: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined. Results: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes. Conclusions: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies. Full article

Background: COVID-19 has been associated with multisystemic sequelae, including persistent neurocognitive impairment and emerging metabolic alterations. Growing evidence suggests that glial dysfunction and inflammation may play a pivotal role in both cognitive decline and new-onset diabetes following SARS-CoV-2 infection. Objectives: This study aimed to assess the prevalence and characteristics of cognitive impairments in post-COVID-19 patients and to explore their correlation with new-onset diabetes, neuroanatomical changes, and psychological symptoms, with a specific focus on gender differences. Methods: A total of 245 patients (mean age 56.8 ± 12 years), previously diagnosed with COVID-19, were enrolled between April 2021 and August 2023. Participants underwent a comprehensive neuropsychological assessment (MMSE, Rey-Osterrieth Figure, FAB, Hamilton, STAI, IES-R), structured interviews, and, in a subset, brain MRI. Individuals with pre-existing neurological disorders were excluded. Data were analyzed for cognitive performance, neuroimaging abnormalities, and metabolic outcomes, including new-onset diabetes. Results: Cognitive dysfunction was identified in 87% of participants: mild in 47%, moderate in 21.6%, and severe in 10.8%. Glial alterations on MRI were observed in 51%, hippocampal atrophy in 9%, and temporal lobe reduction in 4%. Notably, 12% of patients developed new-onset diabetes post-COVID, of whom 80% exhibited mild to moderate cognitive deficits. Depressive symptoms were present in 80.9%, and anxiety in 93.5%, with significantly higher incidence in female patients. PTSD symptoms correlated with greater cognitive impairment. Ongoing research into the mechanisms underlying these persistent cognitive impairments in subjects with and without types 1 and 2 diabetes. This paper presents the final data of the research published in the previous article referenced in the bibliography. Conclusions: This study highlights a significant association between cognitive decline and new-onset diabetes in post-COVID patients, likely mediated by systemic inflammation and glial dysfunction. Particularly noteworthy are the findings of neuroanatomical alterations, including nonspecific glial signal changes, hippocampal atrophy, and temporal lobe volume reductions, suggesting post-infectious cerebral vulnerability with potential long-term consequences. These results support the need for integrating cognitive screening, brain neuroimaging, and metabolic monitoring into post-COVID care pathways—especially for women and individuals presenting with anxiety or depressive symptoms. An early and interdisciplinary approach is essential to address the neuro-metabolic and cerebral sequelae of long COVID. Full article

Background: Obesity is a complex disorder with both metabolic and neurocognitive consequences, including impairments in prefrontal cortex (PFC)-dependent learning and memory. Combination pharmacotherapy may offer a more effective approach for addressing obesity-induced cognitive deficits. Objective: This study evaluated the effects of 30-day co-administration of lorcaserin (5-HT₂C agonist) and betahistine (H₁ agonist/H₃ antagonist) in reversing cognitive deficits in a diet-induced obesity (DIO) rat model. Methods: Male Lewis rats were subjected to DIO and administered lorcaserin (2 mg/kg) and betahistine (5 mg/kg), either alone or in combination, via intraperitoneally implanted osmotic minipumps for 30 days. Y-maze, novel object recognition, and object-in-place (OIP) tests were used to assess cognitive functions. In vivo electrophysiological recordings were employed to examine effects of the combination treatment on ventral tegmental area (VTA) dopaminergic neuron activity. Results: Obese Western-diet-fed rats showed lower discrimination scores in the OIP task, a behavioral test that engages PFC functions, while their performance in the Y-maze and novel object recognition tasks was similar to that of non-obese Control-diet-fed rats. Combination treatment with lorcaserin and betahistine significantly improved the OIP scores of obese rats. However, the combination treatment did not reduce body weight or obesity-associated morphometrical parameters. Electrophysiological recordings revealed a reduction in the number of spontaneously active dopaminergic neurons in the VTA of obese rats. Lorcaserin and betahistine co-treatment significantly increased the number of spontaneously active dopaminergic neurons of obese animals. Conclusions: These results demonstrate the potential of combination lorcaserin–betahistine treatment to reverse obesity-related cognitive deficits, possibly through enhancement of mesocortical dopaminergic neuron activity. Full article

Background/Objectives: Post-stroke cognitive impairment significantly impacts long-term functional outcomes, particularly in instrumental activities of daily living (IADLs). Working memory training (WMT) has emerged as a potential cognitive rehabilitation strategy; however, its transfer to real-world functionality remains unclear. This study evaluated whether adaptive computerized WMT enhances IADLs performance compared to a non-adaptive control condition in chronic stroke survivors. Methods: A single-blind, randomized controlled trial was conducted with 50 adults aged 50–79 years, ≥12 months post-ischemic stroke, and diagnosed with a mild neurocognitive disorder. Participants were randomized to adaptive WMT or non-adaptive cognitive training, each completing 25 home-based sessions over 12 weeks via a standardized online platform. Primary outcomes included the Lawton and Brody IADL Scale and the Working Memory Questionnaire (WMQ); secondary outcomes included the Working Memory Index (WMI) from the WAIS-IV. Analyses included frequentist and Bayesian methods. Results: Both groups showed significant pre–post improvements in IADL independence and WMI (p < 0.05; BF₁₀ > 10), with no significant between-group differences on overall IADL outcomes. The adaptive WMT group demonstrated specific gains in WMQ—Storing (p = 0.033; BF₁₀ = 3.83), while the control group improved in WMQ—Attention and IADL—Assistance Required (p = 0.004–0.035; BF₁₀ > 6). Bayesian ANOVA indicated that these effects were primarily driven by the interventions, with minimal influence from depressive symptoms or global cognition. Conclusions: Adaptive WMT yielded domain-specific cognitive benefits but did not enhance IADL performance beyond non-adaptive training. These findings highlight the limited far transfer of WMT and the importance of designing ecologically valid, multimodal rehabilitation strategies post-stroke. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood and adolescence, characterized by symptoms of inattention, hyperactivity, and impulsivity. These symptoms often interfere with academic, social, and family functioning. In recent years, the use of digital tools and video games has garnered attention as an innovative and engaging approach for neurocognitive rehabilitation. The primary objective of this randomized controlled study was to investigate the comparative effects of two cognitive intervention approaches—one based on new technologies and one using traditional methods—on attention, inhibitory control, and processing speed in children and adolescents diagnosed with ADHD. Thirty-three participants aged 6–17 years were randomly assigned to either an experimental group (n = 17), which received Nintendo Switch-based therapy, or a control group (n = 16), which received traditional board game therapy. Both interventions lasted 8 weeks and included 16 sessions. Outcomes were assessed using the WISC-V, STROOP, and CARAS-R tests. Results showed significant within-group improvements in both groups. The control group exhibited gains in sustained attention and inhibitory control (CARAS-R and STROOP tests, p < 0.05), while the experimental group improved significantly in processing speed, as measured by the WISC-V (p = 0.001). However, no significant differences were found between groups. These findings suggest that both interventions may be effective for enhancing different cognitive processes in children with ADHD. Importantly, the use of familiar digital technologies like the Nintendo Switch may promote greater motivation and adherence to treatment. Further research with larger samples and long-term follow-up is warranted to validate and extend these preliminary findings, as the current sample size was not powered to detect medium or small effects. Full article

mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology. Full article

Background and Objectives: Sleep complaints are particularly relevant in the development of children, affecting cognitive development, neuropsychological functioning, and learning abilities. The aims of this study were as follows: (i) to determine the incidence of sleep disorders in low-risk infants and toddlers with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), using the Italian version of the Sleep Disturbance Scale for Children (SDSC); and (ii) to compare the data with those of a healthy control group. Materials and Methods: This is a cross-sectional case–control study involving a total of 167 infants and toddlers (aged 6–36 months) with HIE treated with TH and 160 typically developing infants assessed using the SDSC filled out by the mother. A neurocognitive assessment was also performed. Exclusion criteria were mild perinatal asphyxia, major brain lesions, congenital malformations, severe postnatal infectious diseases, metabolic complications, cerebral palsy, neurodevelopmental impairment, and epilepsy. Results: In the study group, an abnormal total SDSC score was found in 1.8% of infants; 10% of infants had an abnormal score on at least one of the SDSC factors. No specific differences in the SDSC total and the factor scores were observed between the study and control group, with the exception of difficulties in maintaining sleep and sleep hyperhidrosis, with higher scores in HIE infants. Conclusions: Low-risk infants and toddlers with HIE showed a low incidence of sleep disorders, similar to those observed in control group, with some exceptions. As these incidences may increase significantly with age, further clinical assessments will be needed to confirm these data at older ages. Full article

Background: Developmental dyslexia (DD) is the most common form of specific learning disorders (SLDs). From a neurocognitive point of view, dyslexic reading is associated with atypical neurofunctional patterns in the left hemisphere, mainly in the posterior areas linked to lexical access and phonological processing. Nowadays, rehabilitation treatments do not aim to fix the disorder but rather improve adaptive skills. On the other hand, the transcranial direct current stimulation (tDCS) has recently gained popularity in this field. In fact, a few studies have documented enhanced accuracy and speed after the tDCS over the parietal cortex, although the results were mainly limited to non-word reading. Methods: We conducted a single-case study employing an innovative multifocal eight-channel tDCS aimed at increasing the reading network activity in the left hemisphere and inhibiting the contralateral areas. The participant was a 9-year-old boy with a diagnosis of severe mixed-type specific learning disorder. The high-definition multifocal tDCS was administered over key areas of the frontal, temporal, parietal, and occipital lobes (four 3.14 cm² electrodes per hemisphere) in conjunction with tachistoscope training over a span of 10 weeks, with three sessions per week for a total of thirty sessions. Standardized assessments of reading were carried out at the beginning, at the end of the treatment, and at one- and six-month follow-up. Results: The treatment led to a 77% improvement in the accuracy of passage reading and an 83% improvement in the reading of high-frequency short words, with stable results at the 1- and 6-month follow-up. By contrast, in line with the severity of the disorder, there were only slight improvements in the speed parameter. Conclusions: This is the first study to document such remarkable improvements in reading in a case of severe SLD: if confirmed, these promising findings could pave the way for an effective, non-invasive rehabilitation for SLDs using multifocal tDCS. However, future studies are needed to overcome the limitations of single-case studies, such as the lack of control conditions and quantifiable analysis. Full article

Dementia with Lewy bodies (DLB), the second common primary degenerative neurocognitive disorder after Alzheimer disease (AD), frequently presents concurrent co-pathologies that impact clinical presentation and progression. Neuropathological studies have demonstrated a high prevalence of coexistent AD-related neuropathological changes (ADNC), TAR DNA-binding protein 43 (TDP-43) proteinopathies, and cardiac and aging-related disorders, while frontotemporal lobar degeneration (FTLD) and tau-related syndromes play a minor role as DLB-related co-pathologies. Cerebrovascular lesions, including cerebral amyloid angiopathy, are the most prevalent non-neurodegenerative co-pathologies. Cardiovascular disorders, hypertension, and hyperlipidemia are also frequent comorbidities. Due to their high prevalence and clinical impact on DLB patients, clinical trials should account for these and other co-pathologies in their design and selection. Evaluation of these co-pathologies using and interpreting biomarkers may allow greater clinical diagnostic accuracy and the opportunity to better predict clinical progression. Therefore, there is an increasing need for biomarkers in dementia research. This review discusses the kind and frequency of the different co-pathologies in DLB and their clinical impact. It evaluates the possible value of disease-specific biomarkers and how they are helpful in the assessment and prevention of DLB and its co-pathologies. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article