Search Results (254)

Cognitive impairment is a frequent but heterogeneous consequence of SARS-CoV-2 infection, with objective cognitive deficits not always aligning with subjective cognitive complaints. Age, nutritional status, and stress-related biological pathways may contribute to this variability. The corticotropin-releasing hormone receptor 1 (CRHR1), a key regulator of stress and neuroendocrine responses, represents a biologically plausible candidate for post-infection cognitive vulnerability. In this pilot case–control study, we investigated associations between CRHR1 copy number variations (CNVs), prior viral exposures, and cognitive outcomes in adults following SARS-CoV-2 infection. Objective cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) and RBANS, alongside evaluation of subjective cognitive complaints and depressive symptoms. Analyses accounted for age and circulating levels of vitamins B12, B9, and vitamin D. CRHR1 CNVs affecting specific exons (Exon 1 [210 nucleotides] and Exon 11) were associated with objective cognitive impairment, whereas subjective cognitive complaints were more closely related to depressive symptoms than measurable cognitive deficits. Associations with age and certain viral seropositivities (HSV-1, HSV-2, and Hepatitis A) were also observed with objective cognitive outcomes; however, these findings should be interpreted cautiously given their exploratory nature. This study highlights CRHR1 CNVs as potential modifiers of objectively measured post-COVID-19 cognitive impairment and underscores the importance of distinguishing subjective cognitive complaints from objective cognitive dysfunction, providing a framework for future mechanistic and longitudinal studies. Full article

Introduction: Refractory Status Epilepsy Syndrome is a heterogeneous group of diseases associated with status epilepsy. Literature and definition have been conflicting and confusing in terms of their nomenclatures. New-onset refractory status epilepticus (NORSE) is a syndrome characterized by new onset refractory seizures in a previously health child. Febrile infection-related epilepsy syndrome (FIRES) is a similar syndrome now considered a variant of NORSE and is defined as a febrile event taking place between twenty-four hours and two weeks prior to the commencement of refractory status epilepticus. An autoimmune or inflammatory etiology is often implied in both conditions because infection is rarely identified. Aim: This review provides an update on hypotheses, etiology, pathophysiology, clinical features, diagnosis, laboratory evaluation, treatment, and perspectives for NORSE/FIRES. Methods: A PubMed Clinical Queries search is performed using keywords of NORSE and FIRES, on human subjects up to May 2025. All reviews, systematic reviews, case series and case reports were included. Results: Seizures are typically recalcitrant in NORSE/FIRES. Treatments include anti-seizure medications (ASM), ketogenic diet, immunotherapy (intravenous immunoglobulin ± plasmapheresis ± corticosteroid). The prognosis is usually poor. Most children would suffer refractory epilepsy and associated cognitive impairment if they survived. Guidelines and new consensus on NORSE/FIRES terminology have aided clinicians in managing status epilepticus in a previously healthy child that occurs ± a minor febrile episode. When an autoimmune or paraneoplastic condition is subsequently identified, the condition will be named accordingly. Conclusions: NORSE and FIRES are similar conditions except that vagus nerve stimulation appears to be more efficacious in NORSE than FIRES. We propose to define these heterogeneous and confusing conditions as “NOSES” as a two-criteria syndrome: New Onset + Status Epilepticus Syndrome, lasting for over 24 h despite the use of two standard ASM. Autoimmune, paraneoplastic and infectious encephalitis are specific diagnoses of NOSES with etiology subsequently identified. Full article

Background and objectives: This study examines how sociodemographic, clinical, and psychological factors within the patient–caregiver dyad affect caregiver burden and health-related quality of life (HRQoL) in cognitive impairment. By comparing baseline data with a 1-year follow-up, the research aims to identify key predictors of caregiver burden and well-being. Methods: A longitudinal observational study was conducted in an Italian rehabilitation hospital, recruiting 132 outpatients and their caregivers at baseline, categorized as (a) Mild Cognitive Impairment (MCI, n = 33); (b) dementia (DEM, n = 58); (c) healthy subjects (No-CI, n = 41). One year after baseline assessment (T0), patients were contacted and invited for an in-person follow-up re-evaluation (T1). Most attrition was related to the COVID-19 pandemic. Statistical analyses included non-parametric tests for group comparisons and stepwise multiple linear regression to identify predictors of burden, adjusting for confounders (e.g., age, gender, education, employment, co-residence). Results: A total of 51 subjects (age: 80.0 ± 6.1) and 34 caregivers (age: 58.8 ± 15.9) were evaluated. Patients were balanced by gender (53% males); most were retired (96%), married (62.7%), and cared for by sons (47%) or wife–husband (47%). Caregivers (females: 85%) were married (68.3%) and active workers (46.4%). Over one year, 17 No-CI subjects developed MCI or DEM; 15 MCI patients progressed to DEM. Caregiver HRQoL negatively correlated with distress and burden in MCI and DEM groups. Patient cognitive status, functional abilities, neuropsychiatric symptoms, and gender predicted caregiver burden, emphasizing the interplay between clinical and demographic factors. Conclusions: It is essential to monitor psychosocial factors in both the patient and the caregiver to develop effective prevention and support strategies. Full article

Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral syndrome following infection with SARS-CoV-2, which shares many clinical features with CFS. Both conditions involve chronic immune activation, raising questions about their immunopathological overlap. Objectives: This study aimed to compare immune biomarkers between patients with ME/CFS or Long COVID and healthy controls to explore shared immune dysfunction. Methods: We analyzed lymphocyte subsets, cytokine profiles, psychological status and their correlations in 190 participants, 65 with CFS, 54 with Long COVID, and 70 healthy controls. Results: When compared to healthy subjects, results in both conditions were marked by lower levels of lymphocytes (CFS—2.472 × 10⁹/L, p = 0.006, LC—2.051 × 10⁹/L, p = 0.009), CD8⁺ T cells (CFS—0.394 × 10⁹/L, p = 0.001, LC—0.404 × 10⁹/L, p = 0.001), and NK cells (CFS—0.205 × 10⁹/L, p = 0.001, LC—0.180 × 10⁹/L, p = 0.001), and higher levels of proinflammatory cytokines such as IL-6 (CFS—3.35 pg/mL, p = 0.050 LC—4.04 pg/mL, p = 0.001), TNF (CFS—2.64 pg/mL, p = 0.023, LC—2.50 pg/mL, p = 0.025), IL-4 (CFS—3.72 pg/mL, p = 0.041, LC—3.45 pg/mL, p = 0.048), and IL-10 (CFS—2.29 pg/mL, p = 0.039, LC—2.25 pg/mL, p = 0.018). Conclusions: Notably, there were no significant differences between CFS and Long COVID patients in the tested biomarkers. These results demonstrate that ME/CFS and Long COVID display comparable immune and inflammatory profiles, with no significant biomarker differences observed between the two groups. Full article

Background/Objectives: Creatine monohydrate (CrM) supplementation is well-established for enhancing physical performance and accelerating recovery in several sporting contexts. However, beyond these traditional performance benefits, its effects on sleep metrics and cognitive function have not been thoroughly investigated. This investigation aimed to determine the effect of a loading phase of CrM on sleep metrics, physical performance, psycho-cognitive aspects, and recovery in physically active men. Methods: In a randomized, double-blind, placebo-controlled crossover design, 14 physically active men ingested 20 g/day of CrM or placebo (PL) for 7 days, during which their habitual exercise routines were maintained and standardized across both intervention phases. Sleep metrics were monitored throughout the interventions using wrist-worn actigraphy. On the day following the completion of each supplementation phase, participants rated their sleep quality using the Sleep Subjective Quality (SSQ) scale, and the Hooper questionnaire was used to monitor participants’ well-being status. Physical performance was assessed using the 5 m shuttle run test (5mSRT), which measured total distance (TD), best distance (BD), performance decrement (PD), fatigue index (FI), and the rating of perceived exertion (RPE). Affective valence was determined using the feeling scale (FS) and cognitive function was evaluated using the digit cancellation test (DCT). Recovery and muscle soreness perceptions were evaluated at multiple time points (pre-exercise, 5 min, 24 h, 48 h, and 72 h post-exercise) using the perceived recovery status (PRS) and the delayed onset muscle soreness (DOMS) scales, respectively. Results: During the supplementation, CrM improved sleep quality compared to PL, as measured with the SSQ scale (d = 0.81, p = 0.009), and was associated with an earlier in-bed time (r = 0.60; p = 0.026). However, CrM did not affect sleep latency (t = 0.98; p = 0.35), sleep efficiency (t = 0.018; p = 0.98), or total sleep time (t = 0.25; p = 0.81). After the supplementation phase, CrM resulted in significantly lower muscle soreness scores, as measured by the Hooper questionnaire (d = −0.59; p = 0.046), improved cognitive performance on the DCT (d = 0.77; p = 0.013), and enhanced TD (r = 0.88; p < 0.001) and BD (r = 0.76; p < 0.05) during the 5mSRT. However, CrM did not significantly affect other exercise-related measures such as RPE, fatigue index (FI), or performance decrement (PD) during the 5mSRT, nor did it alter other subjective recovery scales compared to PL, up to 72 h following the end of the supplementation phase (all p > 0.05). Conclusions: A 7-day CrM loading protocol improved subjective sleep quality during the supplementation phase, enhanced cognitive performance, and increased physical output during high-intensity intermittent exercise. CrM also reduced muscle soreness, but did not significantly affect objective sleep parameters, or recovery markers up to 72 h post-exercise. These findings suggest that CrM may offer additional benefits beyond its traditional ergogenic role. Trial Registration: This trial was registered on 18 September 2023 at the Pan African Clinical Trials Registry (PACT) (identifier: PACTR202309597156293). Full article

Background: Apolipoprotein E4 (APOE4) represents a major genetic risk factor for Alzheimer’s disease. Objectives: We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and APOE genotypes in individuals of predominantly African descent aged 55 years and more. Genotyping of two single-nucleotide polymorphisms, rs7412 and rs429358, of the APOE gene was performed. Results: Among 310 individuals, the mean age was 75.64 years, the mean BMI was 25.94 kg/m², and the prevalence of CI was 18.1%. Most subjects were ε3/ε3 carriers (49%), while ε2-carriers and ε4-carriers represented 14.5% and 36.5%, respectively. Older age, the presence of undernutrition, and APOE4 carriers were more frequently found in underweight vs. non-underweight individuals and in those with CI vs. those without CI. The adjusted odds ratios for prevalent CI were nearly four times higher for underweight individuals compared to obese individuals. Those carrying two ε4 alleles exhibited three times the odds of CI (OR = 3.31 (95% CI: 1.15–9.91), p = 0.026) compared to those with no ε4 alleles. Conclusions: In this cross-sectional study, being underweight and carrying the ApoE ε4 allele were independently associated with cognitive impairment. These findings suggest that monitoring weight changes and APOE genotypes in older adults may have clinical significance. Full article

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is a validated alternative to inpatient care for complicated infections, ensuring clinical efficacy, safety, and cost-effectiveness. However, its impact on patient-centered outcomes such as nutritional status, frailty, and cognitive well-being has rarely been studied. Methods: We conducted a multicentric retrospective observational study of patients treated with OPAT between April 2024 and July 2025 in two tertiary care hospitals. Baseline demographics, comorbidities, weight, frailty status (Rockwood Clinical Frailty Scale (CFI)), and infection-related variables were collected. Follow-up assessments evaluated body weight, frailty, and subjective cognitive status. Clinical outcomes, adverse events, and hospital readmissions were recorded. Results: Of 139 patients treated with OPAT, 119 were included in the analysis (56% male, median age 67 years). Common comorbidities were ischemic heart disease (33%), diabetes mellitus (29%), chronic pulmonary disease (22%), and solid tumors (19%). The most frequent infections were urinary tract infections (UTIs) (29%), osteomyelitis (25%), and pneumonia (17%). Multidrug-resistant (MDR) organisms were isolated in 66% of cases. Clinical recovery occurred in 82,5% of patients, while 16% required readmission in the next 30 days; no deaths were reported. Body weight (median 73 vs. 73.0 kg at baseline, p = 0.43) and frailty index (median 2.5 vs. 2.4, p = 0.16) remained stable. Cognitive status was unchanged in 85.6%, declined in 5.9%, and improved in 8.5%. Conclusions: OPAT was confirmed to be clinically robust and well tolerated, with additional potential benefits in preserving weight, frailty status, and cognitive well-being. These findings suggest that OPAT not only ensures infection control but may also protect against hospitalization-related functional decline. Prospective studies incorporating standardized geriatric and cognitive assessments are needed to confirm these preliminary findings and define OPAT’s broader role in holistic patient care. Full article

Fulfilling the demand for functional food with cost safety and environmental sustainability, our novel anthocyanin-enriched functional drink containing the purple waxy corn cob-derived functional ingredient “MP1” showed cognitive enhancing effects with safety in bilaterally ovariectomized rats, a validated model of menopause. Since no clinical evidence that confirms the mentioned effect was available until now, we conducted a two-arm, randomized, double-blind, placebo-controlled, crossover study to confirm the benefits mentioned above. A total of 32 menopausal participants were divided into placebo and MP1 (400 mg) groups, and were subject to a 2-month study period. Safety parameters, working memory and brain components, especially N100 and P300, the negative and positive potentials derived from the event-related potential (ERP) which indicated attention and cognitive processing, together with oxidative stress markers acetylcholinesterase (AChE) and monoamine oxidase (MAO), were assessed at baseline and every month. No serious side effects or toxicity signs were observed. Subjects who consumed MP1 also had decreased N100 and P300 latency, improved working memory and decreased oxidative stress status. Therefore, a byproduct of purple corn can successfully serve as a novel functional ingredient for developing a cognitive enhancer drink with the qualities of safety, cost reduction, and environmental sustainability promotion. Full article

Background: Stroke is a major cerebrovascular disease characterized by disrupted cerebral blood flow, leading to neuronal damage and significant physical, cognitive, and emotional sequelae. While advancements in acute stroke management have improved survival rates, long-term complications such as cognitive impairment and depression continue to hinder recovery. This study addresses these dimensions within the context of ischemic stroke. Aim: The aim of this study was to analyze the cognitive status, functionality, and depressive symptoms in patients with ischemic stroke, exploring interrelations between cognitive, functional, and emotional outcomes to prioritize clinical interventions. Design: This was an analytical, observational, cohort, and prospective study. Methods: The study included 81 subjects diagnosed with ischemic stroke admitted to the Neurology Department of Lucus Augusti University Hospital. Data were collected at three time points—admission, discharge, and follow-up—using validated instruments such as the National Institutes of Health Stroke Scale, Mini-Mental State Examination, Barthel Index, and Beck Depression Inventory. Statistical analyses included Spearman’s correlation, Kruskal–Wallis, and Mann–Whitney tests. Results: Patients with greater cognitive impairment at admission showed poorer functional recovery and higher depressive symptoms during follow-up. Depressive symptoms remained minimal in most cases, but correlations with cognitive and functional deficits were significant. NIHSS scores at admission strongly predicted both functional and emotional recovery, reinforcing its value in early prognosis and therapeutic planning. Conclusions: This study highlights the importance of integrating cognitive, functional, and emotional dimensions into stroke care protocols to optimize patient recovery and improve long-term outcomes. Full article

This study examines how objective (OSES) and subjective (SSES) socioeconomic status influence adolescent moral reasoning through distinct psychological mechanisms. Analyzing 4122 Chinese adolescents (Mage = 14.38), we found SSES enhanced moral internalization via strengthened social identity, while OSES reduced moral stereotyping through cognitive flexibility. Contrary to expectations, parental emotional warmth failed to buffer against SSES-related declines in internalization, with higher SSES predicting reduced internalization across parenting contexts. Results reveal socioeconomic status operates through dual pathways—social identity processes for SSES and cognitive flexibility for OSES—while challenging assumptions about parenting’s protective role. The findings suggest tailored interventions: identity-building programs for SSES-related moral development and cognitive training for OSES-linked reasoning biases, advancing theoretical understanding of moral development in diverse socioeconomic contexts. Full article

Background/objectives: Aging is associated with a decline in physiological and cognitive functions. Periodontitis, a disease affecting the periodontal tissues, increases in prevalence with age. Bacteria and inflammatory mediators resulting from periodontitis can trigger neuroinflammation and potentially accelerate the progression of neurodegenerative diseases. This study aimed to evaluate the association between periodontal status, salivary flow rate, salivary cortisol levels, and cytokine levels with cognitive status in elderly Indonesian subjects. Methods: This cross-sectional study involved 70 participants aged ≥ 60 years from several social institutions in Jakarta and the Dental Hospital, Faculty of Dentistry, Universitas Indonesia. All participants provided written informed consent before the examination. Periodontal parameters, including plaque score, calculus index, bleeding on probing, number of remaining teeth, and functional tooth units, were assessed. Unstimulated salivary flow was collected over five minutes, and salivary cortisol levels were measured. Gingival crevicular fluid samples from the deepest periodontal pockets were collected to measure cytokine levels (TNF-α and IL-1β). Both cortisol and cytokine levels were analyzed using ELISA. Cognitive function was evaluated using the Hopkins Verbal Learning Test. Results: Plaque score, calculus index, and bleeding on probing were moderately associated with cognitive scores (p < 0.05). In contrast, the number of remaining teeth, functional tooth units, periodontitis severity, salivary flow rate, salivary cortisol, and cytokine levels were not significantly associated with cognitive scores (p > 0.05). Conclusions: These findings suggest that elderly individuals with cognitive impairment tend to have poorer periodontal health than those with normal cognitive function. Full article

Background: The relationship between mild cognitive impairment (MCI) and subjective well-being remains poorly understood. We examined associations between cognitive function and well-being domains in community-dwelling older Japanese adults with and without MCI. Subjects and Methods: A cross-sectional analysis of 710 community-dwelling Japanese adults aged 65–75 years was carried out. Well-being was measured using the Philadelphia Geriatric Center Morale Scale (PGCMS score ≥ 13 indicates high well-being), comprising agitation, attitude toward aging, and lonely dissatisfaction subscales. MCI was defined as a Montreal Cognitive Assessment (MoCA) score of 18–25. Multivariable logistic regression examined potential associations between socio-demographic and health factors. Results: Among the participants (mean age 70.0 ± 2.5 years, 49% women), 423 (59.6%) had MCI. The MCI status was not associated with overall well-being (OR 1.06, 95% CI: 0.72–1.57, p = 0.77). However, within the MCI group, each 1-point increase in the MoCA score was associated with lower agitation (OR 1.21, 95% CI: 1.04–1.41) but higher lonely dissatisfaction (OR 0.83, 95% CI: 0.70–0.98, p = 0.02). No associations were observed in the non-MCI group. Conclusions: Cognitive function shows domain-specific rather than global associations with well-being in individuals with MCI. Full article

Our study tracks the development of 105 Roma children between 3 and 5 (median age: 51 months), enrolled in an NGO-aided developmental program. Each child undergoes pre- and post-assessment based on the Developmental Assessment of Young Children (DAYC), a standard tool used to track the progress in early childhood development and detect delays. Data are gathered from three sources, teacher, parent/caregiver and specialist, covering four developmental domains and adaptive behavior scale. There are subjective biases; however, in the post-assessment, the teachers’ and parents’ evaluations converge. The test results confirm significant improvement in all areas ($p<0.0001$), with the highest being in cognitive skills $32.2\%$ and the lowest being in physical development $14.4\%$. We also apply machine learning methods to impute missing data and predict the likely future progress for a given student in the program based on the initial input, while also evaluating the influence of environmental factors. Our weighted ensemble regression models are coupled with principal component analysis (PCA) and yield average coefficients of determination $R^2\approx 0.7$ for the features of interest. Also, we perform k-means clustering in the plane cognitive vs. social–emotional progress and consider the classification problem of predicting the group in which a given student would eventually be assigned to, with a weighted $F_1$-score of $0.83$ and a macro-averaged area under the curve (AUC) of $0.94$. This could be useful in practice for the optimized formation of study groups. We explore classification as a means of imputing missing categorical data too, e.g., education, employment or marital status of the parents. Our algorithms provide solutions with the $F_1$-score ranging from $0.92$ to $0.97$ and, respectively, an AUC between $0.99$ and 1. Full article

Background: Physical activity (PA) and adequate micronutrient intake are essential for brain development and may influence cognitive function and academic achievement. However, few large-scale studies have assessed the combined effects of PA and multi-micronutrient supplementation (MMNS) in school-age children. Methods: A cluster-randomized placebo-controlled trial in four peri-urban Tanzanian schools assigned children to one of four groups: (i) PA alone; (ii) MMNS alone; (iii) PA plus MMNS; or (iv) placebo. Children were followed over two school years with assessments at baseline, 14 months, and 26 months. Cognitive function was assessed using computerized Flanker tasks. Academic achievement was evaluated through end-of-year exams in mathematics and Kiswahili subject scores. Anthropometric measures determined nutritional status. Data were analyzed using generalized estimated equations (GEE). Results: Complete data from 559 children (326 girls, 233 boys) aged 6–12 years showed differing characteristics across groups, particularly age and body mass index. No significant intervention effects on cognitive function were found. MMNS groups (alone or combined with PA) showed significantly higher Kiswahili scores, while PA alone had the lowest performance compared to placebo. No intervention effect was found in mathematics. Sex, hemoglobin level, and baseline measures were key predictors for cognition or academic performance. Conclusions: PA and MMNS interventions showed no significant cognitive or academic improvements versus placebo. Further research should optimize school-based nutrition and PA programs for improved learning outcomes. Full article

Cognitive decline among older people is a growing concern worldwide since it impacts quality of life and independence. Recently, we reported that an epicatechin-enriched product improves cardiometabolic status, physical performance/mobility, and quality of life (QoL) in over-60-year-old subjects. Here, we explored the effects of an (−)-epicatechin-enriched cacao supplement on the cognitive conditions of older and sedentary individuals residing in a community center. Twelve persons with the inclusion criteria were included in this proof-of-concept study. We evaluated reasoning, memory, attention, coordination, and perception using CogniFit software, version 4.6.18. Patients received a mixture of cacao flour and 15 mg of free (−)-epicatechin twice daily for 3 months. The main results from the trial suggested a positive and significant improvement in perception, coordination, reasoning, attention, and memory. Full article