Search Results (3,212)

While most of the Alzheimer’s disease (AD) cases are sporadic and manifest after age 65 (late-onset AD, LOAD), a subset of patients develop symptoms earlier in life (early-onset, EOAD) due to mutations in the PSEN1, PSEN2, or APP genes with an autosomal-dominant inheritance pattern (AD-EOAD). In this study, we examined the association between age of onset (AoO) and first clinical manifestation (FCM) with the APOE and DAOA genotypes, previously described as modifiers of clinical phenotypes in LOAD and EOAD in 88 individuals clinically diagnosed with AD-EOAD due to the PSEN1 A431E variant (39 females, 49 males). We classified the population according to their genotype (APOEε2, APOEε3, and APOEε4 and DAOA G/G, G/A, and A/A) and FCM (cognitive, behavioral, motor, and memory impaired). Memory impairment was the most frequent symptom (51%), followed by motor disturbances (31.8%), cognitive symptoms other than memory (10.4%), and behavioral changes (6.8%). We found a significant association between APOE genotype and AoO (p < 0.001), with the APOEε4 allele being linked to a delayed onset (β = 4.04, SE = 1.11, p = 0.0003). Similarly, individuals with the DAOA rs2391191 A/A genotype showed a significantly later AoO compared to G/G carriers (β = 2.13, SE = 0.96, p = 0.0301). No significant association was found between APOE or DAOA genotypes and FCM. The findings suggest that both the APOEε4 allele and DAOA rs2391191 A/A genotype may act as genetic modifiers of AoO, delaying symptom onset in individuals with AD-EOAD. Further research is needed to elucidate the molecular pathways through which APOE and DAOA influence AD-EOAD progression. Full article

Background/Objectives: Academic stress arises when students perceive that university demands exceed their coping resources, leading to cognitive, behavioral, and physiological stress responses. This study examines the predictive role of academic stressors and sociodemographic variables across five dimensions of stress response. Methods: The sample comprised 1014 Spanish university students (64.5% women, 35.5% men; M = 20.56, SD = 3.50). Participants completed the Academic Stressors Scale (E-CEA) and the Stress Responses Scale (R-CEA). Hierarchical regression analyses were conducted in two blocks: sociodemographic variables were entered in the first block, followed by academic stressors in the second. Results: Academic stressors accounted for substantial variance in all five stress response dimensions: negative thoughts (47.8%), physical exhaustion (39.5%), physical agitation (32.9%), irritability (29.7%), and sleep disturbances (26.8%). The most recurrent predictors were beliefs about performance, exams, and academic overload. In contrast, sociodemographic variables explained a much smaller portion of the variance (5.9%) and were specifically linked to higher irritability among women and younger students, more negative thoughts among students in Arts and Humanities, and fewer physical symptoms and sleep disturbances in students from science and technical fields. Conclusions: The findings reveal that academic stressors are key contributors to psychological distress among university students, highlighting the need for institutional interventions to alleviate the most frequent stressors. Identifying student groups particularly vulnerable to academic stress further supports the implementation of tailored strategies that address the diversity of students’ profiles and needs. Full article

Apolipoprotein A (ApoA) proteins, ApoA-I, ApoA-II, ApoA-IV, and ApoA-V, play critical roles in lipid metabolism, neuroinflammation, and blood–brain barrier integrity, making them pivotal in neurological diseases such as Alzheimer’s disease (AD), stroke, Parkinson’s disease (PD), and multiple sclerosis (MS). This review synthesizes current evidence on their structural and functional contributions to neuroprotection, highlighting their dual roles as biomarkers and therapeutic targets. ApoA-I, the most extensively studied, exhibits anti-inflammatory, antioxidant, and amyloid-clearing properties, with reduced levels associated with AD progression and cognitive decline. ApoA-II modulates HDL metabolism and stroke risk, while ApoA-IV influences neuroinflammation and amyloid processing. ApoA-V, although less explored, is implicated in stroke susceptibility through its regulation of triglycerides. Genetic polymorphisms (e.g., APOA1 rs670, APOA5 rs662799) further complicate disease risk, showing population-specific associations with stroke and neurodegeneration. Therapeutic strategies targeting ApoA proteins, including reconstituted HDL, mimetic peptides, and gene-based approaches, show promise in preclinical models but face translational challenges in human trials. Clinical trials, such as those with CSL112, highlight the need for neuro-specific optimization. Further research should prioritize human-relevant models, advanced neuroimaging techniques, and functional assays to elucidate ApoA mechanisms inside the central nervous system. The integration of genetic, lipidomic, and clinical data offers potential for enhancing precision medicine in neurological illnesses by facilitating the generation of ApoA-targeted treatments and bridging current deficiencies in disease comprehension and therapy. Full article

Performance validity tests (PVTs) and symptom validity tests (SVTs) are central to evaluating neuropsychological test results in clinical adult ADHD assessments. Although their relationships have been widely examined, the constructs these measures assess remain poorly understood in applied contexts. This study investigates the conceptual similarities and distinctions of performance validity measures, i.e., the Groningen Effort Test (GET), the Medical Symptom Validity Test (MSVT), and the Amsterdam Short-Term Memory (ASTM) test, within a comprehensive diagnostic battery for adult ADHD. The diagnostic battery included symptom self-reports and a continuous performance test (CPT). Network and factor analyses investigated these relationships. A three-factor structure was hypothesized, consisting of (1) performance validity measures, (2) continuous performance measures, and (3) symptom reports (including embedded SVTs). Data from a large clinical referral sample (N = 461) of adults with suspected ADHD were analyzed to explore these constructs. Network analysis revealed that the PVTs did not form a cohesive network with CPT measures. Symptom reports, including embedded SVTs, formed their own cluster, separate from performance-based attention measures. Factor analysis rejected a unified construct of performance validity measures. Regression analysis showed that cognitive deficits, education level, and impulsivity predicted ASTM test performance, whilst the MSVT and GET did not. These findings suggest that PVTs should be interpreted in the context of ADHD assessment, particularly in high-stakes forensic evaluations, where the accuracy of performance evaluation is critical. Future research should explore multidimensional models of performance validity, addressing domain-specific underperformance and individual variability in ADHD evaluations. Full article

This study aims to analyze the effects of responsible consumption behavior on impulsive buying, and the mediating role of brand literacy in this relationship. Data collected from 524 Turkish participants using an online survey were analyzed using structural equation modeling (SEM). Responsible consumerism exhibited a negative direct effect on impulsive buying and a positive effect on brand literacy. Brand literacy, in turn, was negatively associated with impulsive buying and partially mediated the responsible consumerism–impulsive buying link. Over-consumption and impulsive buying have received considerable scholarly attention. Yet, only a small number of studies have tested whether value-driven orientations, such as responsible consumerism, can curb these impulses. Even fewer still probe the mediating cognitive role of consumer knowledge (e.g., brand literacy). Furthermore, most existing evidence comes from Western high-income settings. This study addresses that gap by empirically testing the responsible consumerism, brand literacy, and impulsive buying pathway in Türkiye, an emerging and rapidly digitalizing economy. Considering its cross-sectional nature and cultural limitations, this study recommends conducting future longitudinal studies and research in various cultural contexts. Full article

Background/Objectives: Individuals with posttraumatic stress disorder (PTSD) tend to show patterns of elevated cardiovascular disease (CVD) risk earlier in life than the general population. The need for effective interventions for CVD risk-reduction in PTSD is increasingly evident. In this paper we present preliminary results from a longitudinal study of a health behavior intervention, as an adjunct to standard trauma therapy in PTSD. The health behavior intervention addresses CVD-related heath behaviors (physical activity, nutrition, sleep, and stress) in a 12-week program delivered individually in 90-min sessions. Behavior change recommendations included: increased aerobic activity; establishing a balanced diet, enhancing consumption of fruits and vegetables and reducing sugars and fat/saturated fat; incorporating strategies to enhance sleep and lower PTSD-related disruptions (e.g., nightmares); and relaxation and cognitive coping skills to reduce general stress. Methods: Participants were randomized to the health behavior intervention plus standard trauma therapy experimental condition or a standard trauma therapy control group. Outcomes were measured at baseline and after the 12-week intervention phase. Sleep efficiency was measured from actigraphy watches. Physical activity was assessed by self-report and blood pressure was measured using an automated device. The preliminary outcomes are for 29 participants to date who have pre-post data. Results: Sleep efficiency was improved in the intervention group compared to controls (p < 0.05). The intervention group also evidenced significant pre-post increases in moderate physical activity compared to the control group (p < 0.05). Changes in vigorous physical activity did not reach statistical significance in this preliminary sample but the pattern of results are similar to those for moderate activity. Trends toward significance were also observed for pre-post changes in systolic (p = 0.06) and diastolic blood pressure (p = 0.07), with small reductions for the intervention group and increases for the control group. Conclusions: These findings provide preliminary information about the effectiveness of the health behavior intervention on multiple parameters for adults with PTSD. The findings suggest that focusing on health behavior change in multidisciplinary treatments for PTSD may enhance outcomes such as sleep and physical activity and potentially result in greater quality of life. However, the small preliminary sample size reported here should be considered when interpreting the outcomes. Further research may also determine how improvements in health parameters impact other indices of long-term cardiovascular health. Full article

The understanding of hidden emotions—situations in which individuals deliberately express an emotion different from what they genuinely feel—is a key skill in theory of mind (ToM) development. This ability allows children to reason about discrepancies between internal emotional states and external expressions and is closely tied to linguistic development, particularly vocabulary related to mental states, which supports complex emotional reasoning. Children who are deaf or hard of hearing (DHH), especially those born to hearing non-signing families and raised in oral language environments, may face challenges in early language exposure. This can impact the development of social and emotional skills, including the ability to understand hidden emotions. This study compares the understanding of hidden emotions in hearing children (n = 59) and DHH children (n = 44) aged 7–12 years. All children were educated in spoken language environments; none of the DHH participants had native exposure to sign language. Participants completed a hidden emotions task involving illustrated stories where a character showed a certain emotion in front of two observers, only one of whom was aware of the character’s true emotional state. The task assessed children’s understanding of the character’s emotional state as well as their ability to reason about the impact of hiding emotions on the beliefs of the observers. The results showed that the hearing children outperformed their DHH peers in understanding hidden emotions. This difference was not attributed to hearing status per se but to language use. Specifically, children’s spontaneous use of cognitive verbs (e.g., think or know) in their explanations predicted task performance across the groups, emphasizing the role of mental state language in emotional reasoning. These findings underscore the importance of early and accessible language exposure in supporting the emotional and social cognitive development of DHH children. Full article

Alzheimer’s disease (AD) is the most common form of dementia, affecting over 50 million people globally. Since 1906, efforts to understand this neurodegenerative disease and to develop effective treatments have continued to this day. Recognizing docosahexaenoic acid (DHA, 22:6n-3) as a safe, inexpensive and vital nutrient for brain health and cognitive protection due to its key role in brain development and function, this study explores novel, sustainable non-fish sources as potential dietary supplements to prevent or mitigate AD, within a blue biotechnology framework. Forty 5×FAD male mice, five weeks old, were allocated to five body weight-matched dietary groups (n = 8) and fed isocaloric diets based on AIN-93M standard chow for 6 months. Each diet, except the control feed (non-supplemented group), enclosed a modified lipid fraction supplemented with 2% of the following: (1) linseed oil (LSO, rich in alpha-linolenic acid (ALA,18:3n-3)); (2) cod liver oil (fish oil, FO, rich in both DHA and eicosapentaenoic acid (EPA, 20:5n-3)); (3) Schizochytrium sp. microalga oil (Schizo) with 40% of DHA; and (4) commercial DHASCO oil (DHASCO) with 70% of DHA. The different diets did not affect (p > 0.05) growth performance criteria (e.g., final body weight, daily feed intake, and body weight gain) suggesting no effect on the overall caloric balance or mice growth, but n-3 long-chain polyunsaturated-fatty acid (n-3 LCPUFA) supplementation significantly reduced total cholesterol (p < 0.001) and total lipids (p < 0.001). No systemic inflammation was detected in 5×FAD mice. In parallel, a beneficial modulation of lipid metabolism by DHA-enriched diets was observed, with polyunsaturated fatty acid incorporation, particularly DHA, across key metabolic tissues, such as the liver (p < 0.001) and the brain (p < 0.001). No behavioural variations were detected using an open-field test after 6 months of diet (p > 0.05). While mice fed a standard diet or LSO diet showed cognitive deficit, the incorporation of FO, Schizo or DHASCO oils into dietary routine showed promising protective effects on the working memory (p < 0.05) and the last two diets also on the recognition memory (p < 0.05) Increased neuronal count (p < 0.05), reflecting neuronal survival, was clearly observed with the fish oil diet. In turn, the number of TAU-positive cells (p < 0.05) was reduced in the Schizo diet, while β-amyloid deposition (p < 0.01) and the neuroinflammatory marker, IBA1 (p < 0.05), were decreased across all DHA-enriched diets. These promising findings open new avenues for further studies focused on the protective effects of DHA derived from sustainable and underexploited Schizochytrium sp. microalga in the prevention of AD. Full article

Background/Objectives: Olfactory impairment has been proposed as an early marker for Alzheimer’s disease (AD), yet the mechanisms linking sensory decline to genetic and environmental risk factors remain unclear. We aimed to identify early biomarkers and brain network alterations associated with AD risk by multimodal analyses in humanized APOE mice. Methods: We evaluated olfactory behavior, diffusion MRI connectomics, and brain and blood transcriptomics in mice stratified by APOE2, APOE3, and APOE4 genotypes, age, sex, high-fat diet, and immune background (HN). Behavioral assays assessed odor salience, novelty detection, and memory. Elastic Net-regularized multi-set canonical correlation analysis (MCCA) was used to link behavior to brain connectivity. Blood transcriptomics and gene ontology analyses identified peripheral molecular correlates. Results: APOE4 mice exhibited accelerated deficits in odor-guided behavior and memory, especially under high-fat diet, while APOE2 mice were more resilient (ANOVA: APOE x HN, F(2, 1669) = 77.25, p < 0.001, eta squared = 0.08). Age and diet compounded behavioral impairments (diet x age: F(1, 1669) = 16.04, p < 0.001). Long-term memory was particularly reduced in APOE4 mice (APOE x HN, F(2,395) = 5.6, p = 0.004). MCCA identified subnetworks explaining up to 24% of behavioral variance (sum of canonical correlations: 1.27, 95% CI [1.18, 1.85], p < 0.0001), with key connections involving the ventral orbital and somatosensory cortices. Blood eigengene modules correlated with imaging changes (e.g., subiculum diffusivity: r = −0.5, p < 1 × 10⁻³⁰), and enriched synaptic pathways were identified across brain and blood. Conclusions: Olfactory behavior, shaped by genetic and environmental factors, may serve as a sensitive, translatable biomarker of AD risk. Integrative systems-level approaches reveal brain and blood signatures of early sensory–cognitive vulnerability, supporting new avenues for early detection and intervention in AD. Full article

Undergraduate design education faces a structural contradiction characterized by high cognitive load (CL) and relatively low innovation output. Meanwhile, existing generative AI tools predominantly emphasize the generation of visual outcomes, often overlooking the logical guidance mechanisms inherent in design thinking. This study proposes a Dual-Path teaching model integrating critical reconstruction behaviors to examine how AI enhances design thinking. It adopts structured interactions with the DeepSeek large language model, CL theory, and Structural Equation Modeling for analysis. Quantitative results indicate that AI-assisted paths significantly enhance design quality (72.43 vs. 65.60 in traditional paths). This improvement is attributed to a “direct effect + multiple mediators” model: specifically, AI reduced the mediating role of Extraneous Cognitive Load from 0.907 to 0.017, while simultaneously enhancing its investment in Germane Cognitive Load to support deep, innovative thinking. Theoretically, this study is among the first to integrate AI-driven critical reconstruction behaviors (e.g., iteration count, cross-domain terms) into CL theory, validating the “logical chain externalization → load optimization” mechanism in design education contexts. Practically, it provides actionable strategies for the digital transformation of design education, fostering interdisciplinary thinking and advancing a teaching paradigm where low-order cognition is outsourced to reinforce high-order creative thinking. Full article

Background/Objectives: Previous magnetic resonance imaging (MRI) investigations reported brain alterations in anorexia nervosa restricting type (AN-R); however, the number of existing structural neuroimaging studies in the developmental age is limited. Here, we analyzed the volumetric brain differences between adolescent patients with AN-R and control peers, and possible correlations between brain volumes and clinical features. Methods: The sample comprised 47 adolescent females with AN-R (mean age: 15.0 years, SD = 1.4) who underwent structural MRI within one month of admission to a tertiary care university hospital, and 39 typically developing controls matched for sex and age. The patients were clinically characterized by standardized interviews/questionnaires. Using the voxel-based morphometry (VBM) technique, possible significant volumetric brain differences between the two groups were analyzed. Moreover, correlations between altered brain regions and clinical (i.e., body mass index (BMI) and disease duration) or psychopathological variables were investigated. Results: An overall reduction in gray matter (GM) volume with a concomitant increase in cerebrospinal fluid (CSF) is observed in AN-R patients; these alterations correlate with a lower BMI. The reduction in GM volume affects the frontal and parietal regions involved in the cognitive processes that underlie and sustain the AN-R clinical features. Conclusions: These results add to the current knowledge of the AN-R pathophysiology and pave the way for the development of brain imaging biomarkers for AN in the developmental age. Full article

Background: The U.S. Medicare Annual Wellness Visit (AWV) offers a structured opportunity for cognitive screening and personalized prevention planning among older adults. Yet, implementation of AWVs, particularly for individuals with cognitive impairment, remains inconsistent across primary care or other diverse care settings. Methods: We conducted a scoping review using the Consolidated Framework for Implementation Research (CFIR) to explore multilevel factors influencing the implementation of the Medicare AWV’s cognitive screening component, with a focus on how these processes support the detection and management of cognitive impairment among older adults. We searched four databases and screened peer-reviewed studies published between 2011 and March 2025. Searches were conducted in Ovid MEDLINE, PubMed, EBSCOhost, and CINAHL databases. The initial search was completed on 3 January 2024 and updated monthly through 30 March 2025. All retrieved citations were imported into EndNote 21, where duplicates were removed. We screened titles and abstracts for relevance using the predefined inclusion criteria. Full-text articles were then reviewed and scored as either relevant (1) or not relevant (0). Discrepancies were resolved through consensus discussions. To assess the methodological quality of the included studies, we used the Joanna Briggs Institute critical appraisal tools appropriate to each study design. These tools evaluate rigor, trustworthiness, relevance, and risk of bias. We extracted the following data from each included study: Author(s), year, title, and journal; Study type and design; Data collection methods and setting; Sample size and population characteristics; Outcome measures; Intervention details (AWV delivery context); and Reported facilitators, barriers, and outcomes related to AWV implementation. The first two authors independently coded and synthesized all relevant data using a table created in Microsoft Excel. The CFIR guided our data analysis, thematizing our findings into facilitators and barriers across its five domains, viz: (1) Intervention Characteristics, (2) Outer Setting, (3) Inner Setting, (4) Characteristics of Individuals, and (5) Implementation Process. Results: Among 19 included studies, most used quantitative designs and secondary data. Our CFIR-based synthesis revealed that AWV implementation is shaped by interdependent factors across five domains. Key facilitators included AWV adaptability, Electronic Health Record (EHR) integration, team-based workflows, policy alignment (e.g., Accountable Care Organization participation), and provider confidence. Barriers included vague Centers for Medicare and Medicaid Services (CMS) guidance, limited reimbursement, staffing shortages, workflow misalignment, and provider discomfort with cognitive screening. Implementation strategies were often poorly defined or inconsistently applied. Conclusions: Effective AWV delivery for older adults with cognitive impairment requires more than sound policy and intervention design; it demands organizational readiness, structured implementation, and engaged providers. Tailored training, leadership support, and integrated infrastructure are essential. These insights are relevant not only for U.S. Medicare but also for global efforts to integrate dementia-sensitive care into primary health systems. Our study has a few limitations that should be acknowledged. First, our scoping review synthesized findings predominantly from quantitative studies, with only two mixed-method studies and no studies using strictly qualitative methodologies. Second, few studies disaggregated findings by race, ethnicity, or geography, reducing our ability to assess equity-related outcomes. Moreover, few studies provided sufficient detail on the specific cognitive screening instruments used or on the scope and delivery of educational materials for patients and caregivers, limiting generalizability and implementation insights. Third, grey literature and non-peer-reviewed sources were not included. Fourth, although CFIR provided a comprehensive analytic structure, some studies did not explicitly fit in with our implementation frameworks, which required subjective mapping of findings to CFIR domains and may have introduced classification bias. Additionally, although our review did not quantitatively stratify findings by year, we observed that studies from more recent years were more likely to emphasize implementation facilitators (e.g., use of templates, workflow integration), whereas earlier studies often highlighted systemic barriers such as time constraints and provider unfamiliarity with AWV components. Finally, while our review focused specifically on AWV implementation in the United States, we recognize the value of comparative analysis with international contexts. This work was supported by a grant from the National Institute on Aging, National Institutes of Health (Grant No. 1R01AG083102-01; PIs: Tzeng, Kuo, & Raji). Full article

Data on the genetic and environmental factors underlying the co-occurrence of Cognitive Disengagement Syndrome (CDS), Attention Deficit Hyperactivity Disorder (ADHD), and Emotional Dysregulation (ED) are limited. This study aimed to explore the nature of the associations between CDS, ADHD with ED, and to assess the role of shared etiological factors in explaining their comorbidity. We analyzed a sample of 400 Italian twin pairs aged 8–18, from Northern Italy and enrolled in the Italian Twin Registry. Bivariate genetic analyses were conducted using parent-rated CBCL scores for CDS, ADHD, and ED. For both CDS–ED and ADHD–ED associations, the best-fitting models were Cholesky AE models (−2LL = −849.167 and −339.030, respectively; p > 0.05), suggesting that the covariation was mainly due to additive genetic factors (CDS–ED—A = 0.81, 95% CI [0.66–0.95]; ADHD–ED—A = 0.86, 95% CI [0.75–0.95]). More than half of the genes were shown to be shared among the phenotypes. Non-shared environmental contributions were smaller (CDS–ED—E = 0.19, 95% CI [0.05–0.34]; ADHD–ED—E = 0.14, 95% CI [0.05–0.25]), indicating interrelated but distinct constructs. Despite some limitations, particularly the exclusive use of the CBCL, findings highlight the importance of monitoring ED symptoms in individuals with CDS or ADHD, and vice versa. Full article

Background/Objectives: Levels of lipopolysaccharide (LPS), arachidonic acid (AA), and advanced glycation end products (AGEs) are higher in the brain of subjects affected by cognitive impairment and Alzheimer’s disease (AD), compared to a healthy brain. Methods: In this narrative review, articles were selected with data on these three key dietary compounds relevant to neuroinflammation and cognitive impairment in order to provide practical dietary advice to reduce the risk of diseases affecting cognition. Results: Triggered by LPS and AGEs in food, inflammatory cytokines can enter the brain and stimulate microglial activation, inflammation, and oxidative damage. AA can elicit neuroinflammation by increasing leukotriene-A4 and prostaglandin-E2 production. Increased levels of neuroinflammation are associated with poorer cognition in AD. Discussion: A dietary reduction of LPS, AA, and AGEs could slow progression and reduce the risk of cognitive impairment and AD by reducing neuroinflammation through several mechanisms. The avoidance of foods that are highest in LPS, AGEs, and AA (dairy products, pork, poultry, beef, and seafood) and the emphasis on foods lowest in LPS, AGEs, and AA (fruits, vegetables, boiled whole grains, beans, raw nuts, and seeds) can reduce neuroinflammation and risk of cognitive impairment and AD. Conclusions: Reduction of chronic neuroinflammation with dietary changes may represent a novel approach to the treatment of AD and cognitive decline. Full article

In recent years, there has been growing interest in developing robots capable of explaining their behavior, thereby improving their acceptance by humans with whom they share their environment. Proposed software designs are typically based on the advances being made in conversational systems built on deep learning techniques. However, apart from the ability to formulate explanations, the robot also needs an internal episodic memory, where it stores information from the continuous stream of experiences. Most previous proposals are designed to deal with short streams of episodic data (several minutes long). With the aim of managing larger experiences, we propose in this work a high-level episodic memory, where relevant events are abstracted to natural language concepts. The proposed framework is intimately linked to a software architecture in which the explanations, whether externalized or not, are shaped internally in a collaborative process involving the task-oriented software agents that make up the architecture. The core of this process is a runtime knowledge model, employed as working memory whose evolution allows for capturing the causal events stored in the episodic memory. We present several use cases that illustrate how the suggested framework allows an autonomous robot to generate correct and relevant explanations of its actions and behavior. Full article