Search Results (215)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Recent findings suggest that long-term and heavy alcohol consumption can aggravate several pathological processes associated with AD, whereas the impact of light or moderate consumption remains uncertain. Excessive alcohol exposure impairs the structure and function of key brain regions involved in cognition, particularly the hippocampus, prefrontal cortex, amygdala, cerebellum, Basolateral amygdala (BLA), and hypothalamus. Several studies indicate that chronic alcohol consumption affects the brain by multiple mechanisms like increased oxidative stress, microglial activation, neuroinflammation, microtubule instability, tau hyperphosphorylation, and modified amyloid-β turnover. Disruption of cholinergic transmission further contributes to memory deficits and neuronal susceptibility. These alcohol-related alterations closely resemble core features of AD pathology and may accelerate disease progression. Although some epidemiological studies report the potential benefits of low alcohol intake, their interpretation is limited by inconsistent definitions of drinking patterns and the influence of confounding variables. Overall, current evidence supports a dose-dependent relationship in which alcoholism increases vulnerability to AD-related neurodegeneration. Reducing harmful alcohol use may therefore represent a practical approach to lowering long-term dementia risk. This review summarizes the current mechanisms of alcohol induced neuronal damage across different brain regions. Prolonged alcohol consumption accelerates cerebral aging by enhancing oxidative stress, neuroinflammation, disrupting tau protein degradations, and other neuronal damages that intersect with the pathogenesis of AD. Full article

Depression and anxiety disorders are associated with deficits in several cognitive domains. This meta-analytic review assessed the effects of emotional working memory training (eWMT) on depression and anxiety and their related emotional and cognitive domains. Eligible studies were assessed for changes in depression, anxiety, emotion and cognition after eWMT. Methodological quality was assessed using Cochrane Collaboration’s guidelines, and random-effects models aggregated the results of individual studies. Of 1314 studies identified, 16 were included (883 participants; mean age range, 14.35–68.79 years; 70.44% female). Nine studies were high quality, seven were moderate quality, and none were low quality. There was relatively high heterogeneity across studies and study populations. The eWMT significantly reduced depression (standardized mean difference [SMD], −2.04; 95% confidence interval [CI], −3.68 to −0.39; p = 0.02) and anxiety (SMD, −0.44; 95% CI = −0.23 to −0.17; p < 0.001) and significantly enhanced reappraisal (SMD, 0.38; 95% CI, 0.11 to 0.66; p = 0.03) and working memory capacity (SMD, 0.31; 95% CI, 0.10 to 0.53; p < 0.001), with no significant effect on rumination. Training frequency, training environment, and type of control group differentially affected working memory capacity. Our results demonstrated that eWMT alleviated depression and anxiety, but not rumination, and improved the related factors of reappraisal and working memory. Given the limited number of studies and substantial heterogeneity in the data, further research is needed to support these results. Full article

Post-Traumatic Stress Disorder (PTSD) is consistently linked to multidimensional working memory (WM) impairments, encompassing deficits in sustained attention, verbal and visuospatial processing, and executive control, with inhibitory dysfunction emerging as a key feature. This scoping review synthesizes evidence from 39 studies examining neurobiological mechanisms, trauma-related factors, genetic and hormonal influences, gender differences, and task-specific variability. Findings indicated that PTSD is associated with altered activation and connectivity in the prefrontal cortex, hippocampus, and related neural networks, often resulting in compensatory but inefficient recruitment patterns. Emotional distraction and comorbidities such as depression, alcohol use, and traumatic brain injury can exacerbate cognitive deficits. Performance impairments are evident across both emotional and neutral WM tasks, with visuospatial and updating processes being particularly vulnerable. Risk factors include chronic trauma exposure, older age, APOE ε4 allele, and the BDNF Val66Met (rs6265) polymorphism, while modulators such as oxytocin, cortisol, and physical activity show potential cognitive benefits under specific conditions. Methodological heterogeneity and limited longitudinal data restrict generalizability. These findings underscore the importance of early screening, targeted cognitive interventions, and inclusion of underrepresented populations to refine prevention and treatment strategies for PTSD-related WM deficits. Full article

Background/Objectives: Aging-related cognitive decline, linked to oxidative stress and impaired hippocampal neurogenesis, is a major contributor to neurodegenerative disorders. In rodents, this condition can be modeled by D-galactose (D-gal) administration, which induces oxidative stress and recognition memory deficits. Prunus domestica L. (PD), rich in phenolic and flavonoid compounds with antioxidant properties, may counteract such impairments. This study evaluated the effects of PD extract on D-gal-induced memory decline by analyzing its phytochemical content, antioxidant activity, and neuroprotective potential. Methods: Phytochemicals were quantified by colorimetric and pH differential methods, and antioxidant capacity was determined using DPPH and FRAP assays. Male Sprague Dawley rats (12 weeks; n = 12/group) were assigned to 8 groups: vehicle, D-gal, PD (75, 100, or 150 mg/kg), and D-gal + PD (same respective doses). D-gal (50 mg/kg, i.p.) and/or PD were administered by oral gavage daily for 8 weeks. Recognition memory was assessed by the novel object recognition (NOR) test. Hippocampal tissues were processed for immunofluorescence staining of the proliferation marker Ki-67 and superoxide dismutase (SOD) activity using the cytochrome C reduction method. Results: PD extract contained abundant phenolics, tannins, flavonoids, and anthocyanins, and exhibited notable antioxidant activity. D-gal impaired recognition memory, reduced hippocampal cell proliferation, and decreased SOD activity. Co-treatment with PD improved memory performance, enhanced hippocampal neurogenesis, and restored antioxidant enzyme activity. Conclusions: PD extract may protect against D-gal-induced age-related cognitive decline through antioxidant effects and support of hippocampal neurogenesis. Full article

Background and Objectives: MGN-3/Biobran (BRM4, Lentin Plus or Ribraxx) is a natural, rice bran-derived arabinoxylan immunoceutical that modulates the adaptive immune response to viral infections. In response to bacterial infections, basophils act as “first responders” and are also associated with modulation of the adaptive immune response. The maturation of pluripotent CD34⁺ stem cells into basophils is supported by the cytokine interleukin-3 (IL-3). The aim was to test the hypothesis that modulation of the adaptive immune response in bacterial infection by MGN-3/Biobran entails a basophilic response. The tick-related disorder Lyme borreliosis was chosen as the disease model; tick bites are associated with cutaneous IL-3-mediated basophil recruitment. Materials and Methods: A three-month randomised double-blind placebo-controlled trial was conducted in patients with a history of borreliosis who were suffering from symptoms attributable to this disorder. The immunoceutical group received oral Biobran; the dosage for both groups was 1 g thrice daily. Both groups were matched for age, sex, and ethnicity. Results: A higher percentage of basophil count occurred in the immunoceutical group (p = 0.038). The final general linear model included the group (immunoceutical/placebo) and change in fatigue assessed by the 11-item Chalder Fatigue Questionnaire (CFQ) (r² = 0.63; p = 0.0066). The change in basophil count was positively correlated with CFQ change (r_s = 0.633; p = 0.020); only the immunoceutical group showed a positive correlation. Conclusions: These results support the hypothesis being tested. Basophils may modulate the adaptive immune response by acting as immunoregulatory cells. They can regulate the functioning of type 2 T-helper lymphocytes, enhance immunological memory, and present antigens to CD8 T lymphocytes. Further studies are needed to clarify potential mechanistic factors and the timing of this basophilic response. Full article

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterised by the build-up of amyloid beta (Aβ) plaques and neurofibrillary tangles comprising hyper-phosphorylated tau. Increasing evidence indicates that in the early stages of AD, elevated levels of oligomeric forms of Aβ and phosphorylated tau (p-tau) gives rise to impaired synaptic function which ultimately drives AD-associated cognitive abnormalities. Thus, developing drugs that can limit the synaptic impairments that occur early in AD may have therapeutic benefits. Clinical evidence increasingly supports a link between lifestyle choices and AD risk. Indeed, there is an association between the circulating levels of the metabolic hormone leptin, mid-life obesity and disease risk, which has in turn stimulated interest in targeting the leptin system to treat AD. It is well-established that leptin readily accesses the brain, with the hippocampus, a key region that degenerates in AD, identified as a prime target for this hormone. Within the hippocampus, leptin has cognitive enhancing properties as it markedly influences the cellular events underlying hippocampal-dependent learning and memory, with significant impact on synaptic plasticity and trafficking of glutamate receptors at hippocampal excitatory CA1 synapses. Moreover, studies using a range of cell-based systems and animal models of disease indicate not only that leptin has powerful pro-cognitive effects, but also that leptin protects against the unwanted synapto-toxic effects of Aβ and tau, as well as enhancing neuronal cell viability. Moreover, recent studies have demonstrated that smaller leptin-based molecules replicate the full repertoire of protective features of whole leptin. Here we review the evidence that the leptin system is a potential novel avenue for drug discovery in AD. Full article

Background/Introduction: Alzheimer’s disease (AD) is a progressive neurological disorder and one of the leading causes of death among older adults in the United States. It causes gradual cognitive decline, memory loss, and impaired functioning. Vulnerable populations—especially those living in rural and predominantly Black communities like the Mississippi Delta—are disproportionately affected. Despite high Alzheimer’s disease mortality rates in Mississippi, limited research has analyzed recent trends disaggregated by race, gender, and geography. This study evaluated trends in AD mortality in the Mississippi Delta between 2016 and 2022 to inform equitable public health responses. Methods: This trend study used age-adjusted mortality rates (AAMRs) for adults aged 65 and older to examine Alzheimer’s disease deaths. AAMRs allow for fair comparisons across groups by adjusting for differences in population age structures. Mortality data were obtained from the Mississippi Statistically Automated Health Resource System (MSTAHRS), a statewide health surveillance system managed by the Mississippi State Department of Health. Joinpoint regression analysis was used to identify statistically significant changes in mortality trends over time using Annual Percent Change (APC) and Average Annual Percent Change (AAPC), with 95% confidence intervals (CIs). AAPC denotes an average percentage change in mortality trends over a seven-year period. Joinpoint regression is an appropriate method for detecting points at which linear trends change significantly, especially in chronic disease mortality analysis. Results: From 2016 to 2022, Alzheimer’s disease mortality significantly increased among Black individuals (AAPC = 8.3%, 95% CI [2.6 to 16.0]; p < 0.05) and declined among White individuals (AAPC = −2.9%, 95% CI [−12.3 to 7.6] p < 0.05). Gender-specific analyses showed slight, non-significant increases among both males and females. County-level disparities were evident: counties such as Sharkey experienced increases exceeding 10%, while Humphreys counties showed declines. Racial disparities in AD mortality were more pronounced than gender differences. Conclusions: This study reveals widening racial and geographic disparities in Alzheimer’s disease mortality across the Mississippi Delta. The statistically significant increase among Black seniors highlights structural inequities in early diagnosis, access to culturally appropriate care, and chronic disease management. These findings support the need for targeted public health interventions, such as the expansion of rural memory clinics, culturally competent outreach, and Medicaid-supported long-term care. Strengthening surveillance systems like MSTAHRS is critical to tracking disparities and advancing equity in dementia-related mortality. Full article

Background/Objectives: The global aging population faces rising rates of cognitive decline and neurodegenerative disorders. This review explores how physical exercise influences brain health in aging, focusing on mechanisms, moderators, and personalized strategies to enhance cognitive resilience. Methods: A narrative review methodology was applied. Literature published between 2015 and 2025 was retrieved from PubMed, Scopus, and Web of Science using keywords and MeSH terms related to exercise, cognition, neuroplasticity, aging, and dementia. Inclusion criteria targeted peer-reviewed original studies in humans aged ≥60 years or aged animal models, examining exercise-induced cognitive or neurobiological outcomes. Results: Evidence shows that regular physical activity improves executive function, memory, and processing speed in older adults, including those with mild impairment or genetic risk (e.g., APOE ε4). Exercise promotes neuroplasticity through increased levels of BDNF, IGF-1, and irisin, and enhances brain structure and functional connectivity. It also improves glymphatic clearance and modulates inflammation and circadian rhythms. Myokines act as messengers between muscle and brain, mediating many of these effects. Cognitive benefits vary with exercise type, intensity, and individual factors such as age, sex, chronotype, and baseline fitness. Combined interventions—physical, cognitive, nutritional—show synergistic outcomes. Digital tools (e.g., tele-exercise, gamification) offer scalable ways to sustain engagement and cognitive function. Conclusions: Physical exercise is a key non-pharmacological strategy to support cognitive health in aging. It acts through diverse systemic, molecular, and neurofunctional pathways. Tailored exercise programs, informed by individual profiles and emerging technologies, hold promise for delaying or preventing cognitive decline. Full article

The study of molecular mechanisms underlying late-life depression (LLD) is increasingly important in light of population aging. To date, LLD-related molecular brain changes remain poorly understood. Furthermore, environmental factors such as climate change and geography contribute to LDD risks. One overlooked factor might be deuterium—a stable hydrogen isotope—whose concentration in drinking water can vary geographically (~90–155 ppm) and alter the incidence of mood disorders. Conversely, potential effects of natural variations in deuterium content in drinking water on LLD symptoms and brain gene expression remain unknown. We conducted Illumina gene expression profiling in the hippocampi and prefrontal cortexes of 18-month-old C57BL/6J mice, a model of LLD-like behaviors, compared to 3-month-old controls. Separately, aged mice were allowed to consume deuterium-depleted (DDW, ~90 ppm) or control (~140 ppm) water for 21 days and were studied for LLD-like behaviors and Illumina gene expression of the brain. Naïve old mice displayed ≥2-fold significant changes of 35 genes. Housing on DDW increased their hedonic sensitivity and novelty exploration, reduced helplessness, improved memory, and significantly altered brain expression of Egr1, Per2, Homer1, Gadd45a, and Prdx4, among others. These genes revealed significant alterations in several GO-BP and KEGG pathways implicated in inflammation, cellular stress, synaptic plasticity, emotionality, and regeneration. Additionally, we found that incubation of primary neuronal cultures in DDW-containing buffer ameliorated Ca²⁺ influx and mitochondrial potential in a toxicity model, suggesting the involvement of mitochondrial mechanisms in the effects of decreased deuterium levels. Thus, aging induced profound brain molecular changes that may at least in part contribute to LLD pathophysiology. Reduced deuterium intake exerted modest but significant effects on LLD-related behaviors in aged mice, which can be attributed to, but not limited by ameliorated mitochondrial function and changes in brain gene expression. Full article

Long COVID is frequently accompanied by neurocognitive complaints, yet the combined effects of demographic and clinical factors remain unclear. This study examined individuals six months after their most recent SARS-CoV-2 infection using a Demographic/Infection-History form, a Physical and Neurocognitive Symptom Checklist (binary), and the Post-COVID Cognitive Impairment Scale (memory, attention; 5-point Likert). Participants were recruited through convenience sampling from multiple community and online sources. Inclusion criteria required confirmed prior COVID-19 infection, self-perceived or clinically documented Long COVID symptoms, and no history of neurological or severe psychiatric disorders. The final sample consisted of 212 participants (mean age = 39.7 years, SD = 10.5), of whom 67.9% were female, and most held a master’s (35.4%) or bachelor’s (28.3%) degree. Difficulties with retaining new information (57.8%) and concentrating (52.1%) were the most frequent neurocognitive complaints, while severe fatigue after mild activity (23.2%) and chronic fatigue (22.7%) were the most common physical symptoms. Confusion and decision-making difficulty were more frequent among younger participants; women reported greater difficulty retaining new information, and difficulty concentrating varied by education level. A multivariable regression model explained 7% of the variance in total cognitive complaints, identifying education level (β = −0.18, p < 0.01) and number of physical symptoms (β = 0.19, p < 0.01) as significant predictors. Higher educational attainment was associated with fewer cognitive complaints, whereas a greater burden of physical symptoms predicted higher complaint scores. Persistent cognitive difficulties in Long COVID appear closely related to physical symptom burden and protective factors such as education, rather than to infection frequency or sensory dysfunction duration. Findings highlight the need for routine cognitive screening, fatigue-focused management, and longitudinal multimodal research to elucidate underlying mechanisms and recovery pathways. Full article

Functional magnetic resonance imaging (fMRI) is commonly used to investigate the neural bases of aging and psychological disorders. However, the BOLD signal captured by fMRI is affected by many factors that are non-neural in origin. We tested how vascular health risks, which often go unmeasured in neuroimaging studies, and aging interact to modify the shape and/or timing of the HRF, which then affect the differences in patterns of brain activity in a task-evoked memory encoding paradigm. Adult participants (aged 20–74) answered questions about their health and underwent two fMRI tasks: viewing a flashing checkerboard and a memory encoding task. Aging and vascular risk had the largest impacts on the maximum peak value of the HRF. Using a subject-specific HRF resulted in a dampening of brain activity in task-positive and task-negative regions. Across three vascular risk factors, using a subject-specific HRF resulted in more consistent brain regions that reached significance and larger effect sizes compared with the canonical HRF. These findings serve as a cautious tail when interpreting task-evoked fMRI activity, especially in populations experiencing alterations to brain vasculature including many older adults and people with neurocognitive disorders like Alzheimer’s disease and related dementias. Full article

Background/Objectives: Guibi-tang (GBT) and its variant Kami-guibi-tang (KGBT) are traditional East Asian multi-herb formulas prescribed for memory loss, insomnia, and fatigue. Preclinical data suggest multimodal neuroprotective actions, including cholinergic signaling modulation and activation of the cAMP response element-binding protein (CREB)/extracellular signal-regulated kinase (ERK) pathway; however, clinical evidence for cognitive disorders remains scattered. This scoping review aimed to map the breadth, design characteristics, efficacy signals, and safety profile of GBT and KGBT across the full spectrum of cognitive impairment. Methods: Following the Arksey–O’Malley framework and PRISMA-ScR guidelines, seven databases were searched (MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, ScienceON, Scopus, Citation Information by the National Institute of Informatics) from inception to 31 January 2025, for human studies evaluating GBT or KGBT in subjective cognitive decline, mild cognitive impairment (MCI), dementia, or post-stroke cognitive impairment (PSCI). Two reviewers independently screened, extracted, and charted data on study design, participants, interventions, outcomes, and adverse events. Results: Fifteen studies met the inclusion criteria—nine randomized controlled trials, one crossover trial, and five observational reports—enrolling 555 participants (age range, 59–87 years). All were conducted in the Republic of Korea, Japan, or China. GBT or KGBT, given as monotherapy or adjunctive therapy for 4 weeks to 9 months, produced modest but consistent improvements in global cognition (Mini-Mental State Examination/Montreal Cognitive Assessment), memory domains, activities of daily living, and neuropsychiatric symptoms across MCI, Alzheimer’s disease, and PSCI cohorts. Reported adverse event rates were comparable to or lower than those of placebo, usual care, or conventional drugs, and no serious treatment-related toxicity was identified. Conclusions: Current evidence—although limited by small sample sizes, heterogeneous formulations, short follow-up durations, and regional concentration—indicates that GBT and KGBT are well tolerated and confer clinically meaningful cognitive and functional benefits. Standardized, multicenter, placebo-controlled trials with biomarker end points are warranted to confirm long-term efficacy, clarify mechanisms, and guide integrative clinical use. Full article

Background: Cytokines participate in regulating the immune response of lymphocytes. Interleukin 2 (IL-2) is the main modulator of T lymphocyte development, homeostasis, and function, whereas interleukin 7 (IL-7) regulates the development and homeostasis of immune cells and plays a crucial role in the maintenance of memory cells. The study aims to assess the blood IL-2 and IL-7 concentration in relation to the obtained cellular and humoral response in adults, six months after vaccination against COVID-19. Methods: We measured the concentration of IL-2 and IL-7 with ELISA, CoV2-IgG with an indirect chemiluminescence test, and the levels of IFN-γ with interferon gamma release assay (IGRA) post SARS-CoV-2 antigen stimulation. The study group (n = 76; F = 66, M = 10) was divided into 41 individuals, who did not report any chronic disorder (ChrD-Neg), and 35, who did (ChrD-Pos). Results: ChrD-Pos group presented higher IL-7 compared to ChrD-Neg (p = 0.023). Negative correlations were observed in the entire study population between IL-2 and age (R = −0.252, p = 0.028), as well as between IL-7 and IFN-γ (R = −0.295, p = 0.010). We found a positive correlation between IL-2 and IL-7 concentrations in the entire study population (R = 0.305, p = 0.007) and the ChrD-Pos group (R = 0.358, p = 0.035), and people with a positive IGRA result (R = 0.359, p = 0.005). Conclusions: The interaction of IL-2 and IL-7 may be important for achieving post-vaccination immunity, especially in adults with chronic diseases. Age is a factor modifying the post-vaccination response (decreased IL-2), whereas IL-7 may be an important factor in achieving a satisfactory post-vaccine response in people with chronic diseases. Full article

This study examined the relationships between anxiety and executive functioning in Arab Israeli female adolescents diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD), compared to their typically developing peers. The aim was to explore differences in emotional and metacognitive executive functions, as well as how anxiety correlates with these cognitive domains within a culturally specific and gender-sensitive population. Eighty adolescent girls aged 15–18 (40 with ADHD and 40 controls) completed self-report measures assessing anxiety and executive functions using the BRIEF-SR and State-Trait Anxiety Inventory. No significant group differences were found in behavioral aspects of executive functions (inhibition, shifting, emotional control, and monitoring) or in overall anxiety levels. However, the ADHD group demonstrated significantly greater difficulties in all metacognitive executive function domains—including working memory, planning, organization, and task completion—as well as higher scores on the Metacognitive Index and Global Executive Composite. Correlational analyses revealed that anxiety was significantly associated with both behavioral and metacognitive executive dysfunction in the control group. In the ADHD group, however, anxiety was only significantly related to behavioral regulation, not metacognitive functioning. These findings underscore the importance of metacognitive support in interventions for adolescent girls with ADHD. Culturally tailored educational strategies that target working memory, planning, and organizational skills may help improve academic performance and overall adaptive functioning in this underserved population. Full article

Changes in gait are associated with an increased risk of falling and may indicate the presence of movement disorders related to neurological diseases or age-related weakness. Continuous monitoring based on inertial measurement unit (IMU) sensor data can effectively estimate gait parameters that reflect changes in gait dynamics. Monitoring using a waist-level IMU sensor is particularly useful for assessing such data, as it can be conveniently worn as a sensor-integrated belt or observed through a smartphone application. Our work investigates the efficacy of estimating gait events and gait parameters based on data collected from a waist-worn IMU sensor. The results are compared to measurements obtained using a GAITRite^® system as reference. We evaluate two machine learning (ML)-based methods. Both ML methods are structured as sequence to sequence (Seq2Seq). The efficacy of both approaches in accurately determining gait events and parameters is assessed using a dataset comprising 17,643 recorded steps from 69 subjects, who performed a total of 3588 walks, each covering approximately 4 m. Results indicate that the Convolutional Neural Network (CNN)-based algorithm outperforms the long short-term memory (LSTM) method, achieving a detection accuracy of 98.94% for heel strikes (HS) and 98.65% for toe-offs (TO), with a mean error (ME) of 0.09 ± 4.69 cm in estimating step lengths. Full article