Prospective Memory Research Articles

Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice

Background and aimsNeuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen’s effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice. MethodsSix-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26-28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA). ResultsHRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2'-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice. ConclusionsThese findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice.

Cutting-Edge Strategies for Overcoming Therapeutic Barriers in Alzheimer's Disease.

Alzheimer's disease (AD) remains one of the hardest neurodegenerative diseases to treat due to its enduring cognitive deterioration and memory loss. Despite extensive research, few viable treatment approaches have been found; these are mostly due to several barriers, such as the disease's complex biology, limited pharmaceutical efficacy, and the BBB. This presentation discusses current strategies for addressing these therapeutic barriers to enhance AD treatment. Innovative drug delivery methods including liposomes, exosomes, and nanoparticles may be able to pass the blood-brain barrier and allow medicine to enter specific brain regions. These innovative strategies of medicine distribution reduce systemic side effects by improving absorption. Moreover, the development of disease-modifying treatments that target tau protein tangles, amyloid-beta plaques, and neuroinflammation offers the chance to influence the course of the illness rather than only treat its symptoms. Furthermore, gene therapy and CRISPR-Cas9 technologies have surfaced as potentially groundbreaking methods for addressing the underlying genetic defects associated with AD. Furthermore, novel approaches to patient care may involve the utilization of existing medications having neuroprotective properties, such as those for diabetes and cardiovascular conditions. Furthermore, biomarker research and personalized medicine have made individualized therapy approaches possible, ensuring that patients receive the best care possible based on their unique genetic and molecular profiles.

Remnant cholesterol and cognitive function: Evidence from the China health and retirement longitudinal study.

Evidence on associations of remnant cholesterol (RC) and its variability with cognitive function is still lacking. To explore the association of RC and its variability with cognitive function. Participants were recruited from a population-based cohort, the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed by a standardized questionnaire from CHARLS, with domains of episodic memory and mental intactness. A linear mixed effects model was used to analyze the association of RC with cognitive function, along with its variability (calculated as standard deviation [SD], coefficient of variation [CV], variability independent of the mean [VIM]), with results expressed as β (95%CI). Potential subgroup differences in the association of RC and its variability with cognitive function were also explored. 4234 participants were eventually included, with mean (SD) age of 57.4 (8.0) years. Each 10 mg/dL increase in RC was associated with 0.053 (95%CI: 0.096, 0.009) points, 0.021 (95%CI: 0.042, 0.000) points, 0.032 (95%CI: 0.064, 0.001) points decrease in global cognitive function, episodic memory, and mental intactness scores, respectively. Compared with the first tertile (T1) group of RC variability (calculated as SD, VIM), T3 showed a lower level in global cognition and episodic memory after multivariate adjustment. The potential modification effects of educational level on RC and its variability in relation to cognitive function were also identified. Among Chinese middle-aged and older adults, higher RC level were associated with worse cognitive function. Greater RC variability was also associated with worse cognitive performance, especially in memory function.

Interplay and long-lasting effects of maternal low-level Pb, Hg, and Cd exposures on offspring cognition

Lead (Pb), mercury (Hg), and cadmium (Cd) are prevalent and persistent environmental contaminants, causing detrimental effects on millions of individuals worldwide. Our previous research demonstrated that early-life exposure to low-level Pb, Hg, and Cd mixtures may lead to cognitive impairments. However, the association and interaction among low levels of Pb, Hg, or Cd exposure remains unclear. In this study, a two-level full factorial design (5.481, 0.036, and 2.132 mg/L for Pb, Hg, and Cd respectively) was conducted to assess the interplay among maternal Pb, Hg, and Cd exposure on offspring cognition. Following exposure during pregnancy and lactation, a competitive absorption among Pb, Hg, and Cd was observed. Maternal exposure to each metal alone resulted in higher blood and brain concentrations of Pb, Hg, and Cd in offspring compared to co-exposure at equivalent levels. However, behavioral experiments conducted in the Morris water maze and novel object recognition test revealed maternal Pb, Hg, and Cd exposure synergistically impaired offspring's spatial cognition and recognition memory. Importantly, this dysfunction persisted into middle age even without exposure after adulthood. Moreover, the open field test and elevated plus maze indicated maternal low-level Pb, Hg, and Cd co-exposure triggered risk-taking behavior in weaning offspring, with a significant main effect for Pb exposure. No long-lasting effect on risk-taking behavior was detected in middle-aged offspring. Further investigation into molecular mechanisms showed that the dysregulation of corticosterone reaction and immune response might be the potential mechanism underlying Pb, Hg, and Cd co-exposure-induced cognitive impairments. Our study highlights the synergistic and long-lasting effects of multiple heavy metal exposures,underscoring the urgency to prevent exposure to metal mixtures among children and women of childbearing age.

Orexinergic modulation of chronic jet lag-induced deficits in mouse cognitive flexibility.

Cognitive flexibility and working memory are important executive functions mediated by the prefrontal cortex and can be impaired by circadian rhythm disturbances such as chronic jet lag (CJL) or shift work. In the present study, we used mice to investigate whether (1) simulated CJL impairs cognitive flexibility, (2) the orexin system is involved in such impairment, and (3) nasal administration of orexin A is able to reverse CJL-induced deficits in cognitive flexibility and working memory. Mice were exposed to either standard light-dark conditions or simulated CJL consisting of series of advance time shifts. Experiment (1) investigated the effects of a mild CJL protocol on cognitive flexibility using the attentional set shifting task. Experiment (2) used a stronger CJL protocol and examined CJL effects on the orexin system utilizing c-Fos and orexin immunohistochemistry. Experiment (3) tested whether nasal orexin application can rescue CJL-induced deficits in cognitive flexibility and working memory, the latter by measuring spontaneous alternation in the Y-maze. The present data show that CJL (1) impairs cognitive flexibility and (2) reduces the activity of orexin neurons in the lateral hypothalamus. (3) Nasal administration of orexin A rescued CJL-induced deficits in working memory and cognitive flexibility. These findings suggest that executive function impairments by circadian rhythm disturbances such as CJL are caused by dysregulation of orexinergic input to the prefrontal cortex. Compensation of decreased orexinergic input by nasal administration of orexin A could be a potential therapy for CJL- or shift work-induced human deficits in executive functions.

Characterization of gut microbiota dynamics in an Alzheimer’s disease mouse model through clade-specific marker-based analysis of shotgun metagenomic data

Alzheimer’s disease (AD) is a complex neurodegenerative disorder significantly impairing cognitive faculties, memory, and physical abilities. To characterize the modulation of the gut microbiota in an in vivo AD model, we performed shotgun metagenomics sequencing on 3xTgAD mice at key time points (i.e., 2, 6, and 12 months) of AD progression. Fecal samples from both 3xTgAD and wild-type mice were collected, DNA extracted, and sequenced. Quantitative taxon abundance assessment using MetaPhlAn 4 ensured precise microbial community representation. The analysis focused on species-level genome bins (SGBs) including both known and unknown SGBs (kSGBs and uSGBs, respectively) and also comprised higher taxonomic categories such as family-level genome bins (FGBs), class-level genome bins (CGBs), and order-level genome bins (OGBs). Our bioinformatic results pinpointed the presence of extensive gut microbial diversity in AD mice and showed that the largest proportion of AD- and aging-associated microbiome changes in 3xTgAD mice concern SGBs that belong to the Bacteroidota and Firmicutes phyla, along with a large set of uncharacterized SGBs. Our findings emphasize the need for further advanced bioinformatic studies for accurate classification and functional analysis of these elusive microbial species in relation to their potential bridging role in the gut-brain axis and AD pathogenesis.

Investigating the Potential Impact of LH on the Progression of Alzheimer’s Disease via Microglia Activation and C/EBPβ pathway

Background: Alzheimer’s disease (AD) is a neurodegenerative disease that causes irreversible cognitive decline and memory loss. The disproportionate effect of AD on postmenopausal women prompts investigation into the role of hormonal changes in disease pathogenesis. However, previous studies on estrogen replacement therapies have shown inconsistent results. Therefore, further confirmation is needed to ensure the independent effects of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on AD pathology. Our study will 1) focus on microglial activation pathway 2) focus on the LH-C/EBPβ-AEP pathway and its potential influence on AD progression.Methods: Using cell lines to investigate whether microglial activation is present. HMC3 cells will be treated with LH or control phosphate buffered saline (PBS). Carry out Western Blot (WB) and qPCR to confirm presence of cytokines, which is the product of microglial activation. Using 3xTg-AD mice treated with LH or control PBS. To identify AD progression, immunofluorescent (IF) micrograph will be used to quantify amyloid-beta (Aβ) load. WB and qPCR will be used to identify cytokines. Morris water maze (MWM) will be carried out for cognitive testing. Using an ovariectomized mice model to investigate the LH-C/EBPβ-AEP pathway. Mice will be treated with LH antibodies or control IgG, followed by assessments using IVIS imaging and MWM test to measure spatial memory. IF, WB and qPCR will be used to quantify Aβ and Tau protein levels and gene expression changes. Furthermore, the study will explore the precise relationship between LH and C/EBPβ expression through inhibition experiments targeting AKT and ERK1/2 signaling pathways.Expected results: Our hypothesis is that LH activates microglia, with both pro-inflammatory and anti-inflammatory cytokine released. This change in microglia function suggests LH has an effect on microglia and hence removal of Aβ plaques. Another hypothesis is that LH antibody manages to cross the blood-brain barrier. The cognitive ability will be improved in LH-Ab treated mice with reduced Aβ and Tau protein levels and downregulation of the C/EBPβ–AEP/δ-secretase pathway. Simultaneously, we expect that there will be a positive correlation between LH levels and expression of C/EBPβ-related pathways, suggesting the involvement of AKT and ERK1/2 signaling pathways in AD progression.Conclusion: This study aims to provide evidence for the link between LH activation of the C/EBPβ pathway and AEP production, promoting our understanding of AD pathogenesis. The insights gained may implicate therapeutic strategies targeting LH mechanisms in postmenopausal women at risk of AD.

A microglia-containing 3D human brain organoid for studying HSV-1-induced Alzheimer’s disease

Alzheimer’s disease (AD), recognized for its profound incapacitation, presents with notable cognitive decline and memory deficits. A growing body of research points to a link between infection with herpes simplex virus type 1 (HSV-1) and the exacerbation of AD. Our study pioneers the use of a cutting-edge, three-dimensional human brain organoid model enriched with microglia, referred to as MC-HBO, to explore the mechanisms by which HSV-1 influences the pathogenesis of AD. Through this model, we examined the regulatory effects of cytokines on amyloid-β (Aβ) deposition, a cardinal pathological manifestation of AD. Our findings demonstrate that the suppression of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), leads to a significant reduction in Aβ deposition. In contrast, the inhibition of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and interleukin-4 (IL-4), was correlated with an increase in Aβ accumulation. These insights into the role of cytokine signaling pathways suggest a promising therapeutic strategy for potentially decelerating the progression of AD.

Chronic Sleep Deprivation Altered the Expression of Memory-Related Genes and Caused Cognitive Memory Dysfunction in Mice.

Lack of sleep, whether acute or chronic, is quite common and negatively affects an individual's memory and cognitive function. The question of whether chronic sleep deprivation (CSD) causes cognitive impairment to arise and progress is not well studied. To investigate the effects of CSD on memory and cognition, this study began by establishing a CSD mouse model. Behavioral experiments on animals revealed that CSD induced cognitive behavioral abnormalities reminiscent of Alzheimer's disease. Western blot experiments further demonstrated a considerable increase in amyloid-β (Aβ) expression in the mouse brain following CSD. Meanwhile, the hub gene Prkcg was searched for in the cerebellum using RNA-seq and bioinformatics analysis. PKCγ (Prkcg) expression was significantly reduced, as demonstrated by RT-qPCR and Western blot validations. Additionally, CSD was associated with downregulated CREB expression, decreased expression of the endothelin-converting enzyme (ECE1), and increased phosphorylation of ERK1/2 downstream of PKCγ. These findings suggested that CSD down-regulated PKCγ expression, decreased ECE1 expression, impaired Aβ degradation, and affected the PKCγ/ERK/CREB pathway and the synthesis of memory-related proteins. Overall, this study highlighted how CSD modulated PKCγ-related metabolism, impacting Aβ clearance and the production of memory-related proteins. Such insights are crucial for understanding and preventing sporadic Alzheimer's disease (sAD) associated with CSD.

Environmental therapy: interface design strategies for color graphics to assist navigational tasks in patients with visuospatial disorders through an analytic hierarchy process based on CIE color perception.

Environmental therapy theory has been applied in the research of disease prevention, and the effectiveness of using color and graphic designs to assist patients with spatial orientation has been confirmed. Visual-spatial impairments are common symptoms associated with cognitive decline. However, the interaction and driving factors between these impairments and spatial color and graphic designs remain unclear. This paper first discusses the correlation between the characteristics of visual-spatial impairments and environmental factors and then investigates the color preferences of such patients based on the CIE 1976 color system and the Analytic Hierarchy Process (AHP). Subsequently, the paper explores spatial design strategies conducive to spatial orientation from the perspective of adaptability to pathological characteristics, utilizing case study analysis. (1) Pathological characteristics of visual-spatial impairments (such as difficulties in spatial orientation and spatial neglect) are related to environmental factors; (2) Emotional attachment factors play a key role in patients' perception of satisfaction with environmental colors; (3) Color associations have the potential to strengthen spatial memory. Additionally, interface designs with high luminance, low saturation, and clear color differentiation facilitate patients' recognition of space. This paper posits that spatial interface design is a feasible approach to assist with spatial orientation, and it achieves this through a mediating process that progresses from influencing visual stimuli to cognitive memory and then to behavioral orientation. The article provides insights into the operational feasibility of this method.

Subjective memory complaints and the effect of a multidomain lifestyle intervention on cognition - the FINGER trial.

Older people reporting subjective memory complaints (SMCs) may have greater risk of cognitive decline. Multidomain lifestyle interventions are a promising strategy for the prevention of cognitive decline. The aim of this study was to investigate whether the presence of SMCs affects the efficacy of a 2-year multidomain lifestyle intervention on cognition. This study is part of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) project. Participants (a sub-sample of 568 individuals, baseline age 60 to 77 years) were randomized (1:1) to receive a 2-year multidomain lifestyle intervention group including dietary advice, exercise, cognitive training, and vascular risk management, or regular health advice control group. Cognitive performance was assessed at baseline and at 1- and 2-year visits, using a neuropsychological test battery, including tests assessing memory, executive functions, and processing speed. Participants rated the frequency of SMCs using the Prospective and Retrospective Memory Questionnaire. Having more retrospective SMCs was linked to a less favorable cognitive trajectory over 2 years. The difference between the intervention and control groups in annual change in tested memory performance was 0.077 (95 % CI 0.008-0.146) among those reporting more retrospective SMCs and -0.011 (-0.074-0.053) among those with less SMCs; interaction effect p=0.019. No other interactions between SMCs and intervention allocation were observed. A lifestyle intervention may be beneficial for older adults with and without SMCs. Persons having more retrospective SMCs may benefit more from the intervention regarding memory functioning.

In Silico and ADMET Studies of Spiro-Quinazoline Compounds as Acetylcholine Esterase Inhibitors Against Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge. Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites. The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives. The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.

A Comparative Analysis of Neurocognitive Function in Community- and Hospital-Based Patients With Schizophrenia.

The study compared differences in various neurocognitive characteristics across treatment modalities among schizophrenia patients recruited in one city between July 2020 and June 2023 who were on regular medication. Of the 151 participants, 113 were included in the analysis. Participants were divided into community-based and hospital-based groups, and their demographics and clinical characteristics, including insight, quality of life, positive and negative symptoms, and personal and social functioning, were examined. In addition, several aspects of cognition were assessed using neurocognitive assessments such as the Trail Making Test (TMT), Stroop test, and Wisconsin Card Sorting Test (WCST). After adjusting for age differences between groups, the final analysis included data from 42 participants in the community-based group and 33 participants in the hospital-based group. Hospital-based group participants completed Stroop-W more rapidly, excelled in Rey-Osterrieth Complex Figure Test recall and recognition, and incurred fewer TMT Part B (TMT-B) and Stroop-C errors. Additionally, they outperformed in WCST total, non-persistent errors, and categories completed. Contrastingly, community-based group participants showed superior outcomes in WCST persistent responses and errors, suggesting specific neurocognitive strengths. We found differences in neurocognitive characteristics between the two groups. These differences were consistent across a range of cognitive domains, including attention, visual discrimination, memory, and executive functioning. Further large-scale study is needed to generalize cognitive characteristics across treatment modalities.

Sleep Disorders in Alzheimer’s Disease

Alzheimer’s disease is the leading cause of dementia worldwide. Patients typically exhibit cognitive impairment, memory loss, diminished social and occupational functioning, as well as language and motor disorders. Alzheimer’s disease is characterized by the abnormal accumulation of amyloid-β (Aβ) and phosphorylated tau in the brain. These pathological changes not only disrupt neuronal function and lead to cognitive deficits, but also interfere with sleep regulation, resulting in sleep disorders. Such disturbances can diminish nighttime sleep quality and contribute to daytime functional impairments, further exacerbating cognitive decline. Therefore, exploring the interplay between cognitive impairment, Alzheimer’s disease, and sleep disorders is crucial for enhancing the quality of life of Alzheimer’s patients. This review summarizes current literature on the interconnections among Alzheimer’s disease, cognitive impairment, and sleep disorders. Sleep disturbances are prevalent in Alzheimer’s patients and can also occur in those with amnestic mild cognitive impairment, which often precedes Alzheimer’s onset. Such sleep disorders may promote and accelerate the accumulation of amyloid-β and tau proteins [1-3]. Furthermore, Alzheimer’s patients may be more vulnerable to sleep disturbances, creating a potential vicious cycle. Further investigation into these relationships may provide valuable insights for the treatment or prevention of Alzheimer’s disease.

Effects of a Functional Cone Mushroom (Termitomyces fuliginosus) Protein Snack Bar on Cognitive Function in Middle Age: A Randomized Double-Blind Placebo-Controlled Trial.

Background: Due to the rising prevalence of cognitive impairment in the middle-aged and elderly population, combined with consumer demand for functional foods to improve health and well-being. Objective: This study aimed to formulate a functional cone mushroom (Termitomyces fuliginosus) (FCM) protein snack bar and evaluate its amino acid profile, phytochemical contents, biological activity and impact on cognitive function. Methods: A total of 26 middle-aged male and female participants were randomized and divided into placebo, FCM1 and FCM2 groups. Continuous consumption was performed for 6 weeks. Demographic data, body composition, cognitive function and memory were evaluated at baseline and at the end of the study period (6 weeks). Results: The event-related potential (ERP) analysis results showed a significant increase in N100 and P300 amplitude at the Fz location in participants who consumed the functional cone mushroom protein snack bar at a dose of 1 g compared to the placebo group (p = 0.015). Additionally, subjects who consumed the functional cone mushroom protein snack bar at a dose of 2 g showed a significantly increased P300 amplitude and percent accuracy of numeric working memory (p = 0.048) compared to those in the placebo group (p = 0.044). The possible underlying mechanism may involve AChE and MAO suppression activity alongside antioxidant activity. Conclusions: These data suggest that FCM can improve cognitive function and memory and may be considered for use in natural supplementation products with possible health benefits.

Physical Activity Regulates and Mediates the Signaling Pathway and Pathophysiological Mechanisms of the Neuroinflammation and Neurodegenerative

Context: The correlation between neuroinflammation and neurodegenerative disorders has been extensively documented. Elevated levels of inflammatory cytokines in the bloodstream have been demonstrated to impair memory function and heighten susceptibility to neurodegenerative disorders. Furthermore, elevated quantities of reactive oxygen species (ROS) in the body, known as oxidative stress, exacerbate neurodegenerative illnesses and negatively affect learning and memory. Neuroprotection prevents neuronal cell death by intervening and blocking the pathogenetic process that leads to cellular malfunction and death. Methods: We evaluated several studies in the WEB of SCIENCE, SCOPUS, and PubMed. Furthermore, we identified the central genes and signaling pathways associated with neurogenesis, the neural system, and neuroplasticity through data mining, a literature review of artificial intelligence, and an in-silico study. Results: Physical exercise (PE) benefits various physiological systems, including the central nervous system. The beneficial impacts of physical activity on cognitive performance, neural well-being, and safeguarding neurons against different brain injuries are extensively documented. Furthermore, research has demonstrated that PE is a powerful non-pharmacological intervention that enhances cognitive function, including learning and memory, while decreasing the likelihood of developing neurodegenerative disorders. Additionally, engaging in moderate physical activity that does not result in extreme fatigue has a beneficial impact on reducing inflammation and promoting antioxidant effects. According to the hormesis theory, physical inactivity and extreme overtraining can decrease physiological function. Conclusions: In summary, a combination of moderate aerobic exercise, HIIT, and resistance training, performed at appropriate intensities, is most beneficial for neuroprotection and cognitive health. Regular engagement in these activities can help mitigate the risk of neurodegenerative diseases and enhance overall brain function.

Long-term cognitive training enhances fluid cognition and brain connectivity in individuals with MCI

Amnestic mild cognitive impairment (aMCI) is a risk factor for Alzheimer’s disease (AD). Multi-domain cognitive training (CT) may slow cognitive decline and delay AD onset. However, most work involves short interventions, targeting single cognitive domains or lacking active controls. We conducted a single-blind randomized controlled trial to investigate the effect of a 6-month, multi-domain CT on Fluid Cognition, functional connectivity in memory and executive functioning networks (primary outcomes), and white matter microstructural properties (secondary outcome) in aMCI. Sixty participants were randomly assigned to either a multi-domain CT or crossword training (CW) group, and thirty-four participants completed the intervention. We found a significant group-by-time interaction in Fluid Cognition (p = 0.007, F (1,28) = 8.26, Cohen’s d = 0.38, 95% confidence interval [CI]: 2.45–14.4), with 90% of CT patients showing post-intervention improvements (p < 0.01, Cohen’sd = 0.7). The CT group also showed better post-intervention Fluid Cognition than healthy controls (HCs, N = 45, p = 0.045). Functional connectivity analyses showed a significant group-by-time interaction (Cohen’s d ≥ 0.8) in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex (IPC) networks. Specifically, CT displayed post-intervention increases whereas CW displayed decreases in functional connectivity. Moreover, increased connectivity strength between the left DLPFC and medial PFC was associated with improved Fluid Cognition. At a microstructural level, we observed a decline in fiber density (FD) for both groups, but the CT group declined less steeply (1.3 vs. 2%). The slower decline in FD for the CT group in several tracts, including the cingulum-hippocampus tract, was associated with better working memory. Finally, we identified regions in cognitive control and memory networks for which baseline functional connectivity and microstructural properties were associated with changes in Fluid Cognition. Long-term, multi-domain CT improves cognitive functioning and functional connectivity and delays structural brain decline in aMCI (ClinicalTrials.gov number: NCT03883308).

Witnessing their mother’s acute and prolonged stress affects executive functioning in children

Stress can detrimentally affect physical and mental health, especially during childhood. During this critical period, parental bonds can foster resilience or amplify stress. This study explored whether mothers’ everyday stress can act as a source of childhood stress, affecting children’s executive functioning. 76 healthy mother-child dyads participated, with mothers assigned to a stress-inducing or stress-free condition. Children observed their mothers and were subsequently tested for cognitive flexibility and working memory. Subjective stress, heart rate, and cortisol were measured repeatedly in mothers and children, alongside everyday stress perceptions. Linear mixed models showed that children’s acute stress response was associated with impaired cognitive flexibility. Maternal stress, both acute and past-month, was a better predictor of children’s cognitive performance than children’s own stress. Quadratic relationships indicated the highest error rates at very low and high maternal stress. We found no evidence that children’s working memory was impaired by their own or their mothers’ stress. Although expected covariations of acute or prolonged stress between mothers and children were not observed, an interaction between maternal past-month stress and acute stress condition provided insights into adaptive mechanisms in children. These findings underscore the significant impact of maternal stress on children’s executive functioning, illustrating how parental experiences shape children’s everyday outcomes.

Queen Bee Larva, an Edible By-Product of Royal Jelly, Alleviate D-Galactose-Induced Aging in Mouse by Regulating Gut Microbiota Structure and Amino Acid Metabolism

Queen bee larva (QBL), as a by-product of royal jelly, is a kind of protein-rich edible insect. However, the development and utilization of QBL have been very limited for an extended period, resulting in considerable economic waste. Notably, QBL has substantial potential for anti-aging treatments; however, systematic studies have been scarce. The present study aimed to analyze the effects of freeze-dried QBL powder (QBLP) treatment in a D-galactose (D-gal)-induced-aging mouse and to explore the mechanisms. A behavioral test indicated that QBLP-treated mice had improved cognitive function and memory decline caused by aging compared to untreated aged mice. Furthermore, QBLP treatment improved organ index in aged mice and prevented pathological damage to the brain tissue. Concomitantly, treatment of D-gal-induced-aging mice with QBLP significantly reduced the oxidative damage of serum and increased the skin moisture content of aging mice. Finally, integrated analyses of the gut microbiota and the serum metabolome showed that QBLP supplementation altered the composition of the gut microbiota, enriched biochemical pathways associated with amino acid metabolism, and adjusted serum concentrations of beneficial free amino acids. Overall, QBLP can improve symptoms related to D-gal-induced aging in mice by regulating gut microbiota structure and amino acid metabolism.

Effects of an individual cognitive stimulation intervention on global cognition, memory, and executive function in older adults with mild to moderate Alzheimer's disease.

To determine the efficacy of a 12-week individual cognitive stimulation (iCS) intervention on global cognition, memory, and executive function of older adults with mild to moderate Alzheimer's disease (AD). Protocolized analysis using data from a multicenter, single-blind, randomized, parallel two-arm RCT of iCS for older adults with probable AD. A sample of 142 people with probable Alzheimer's disease attending 13 Portuguese institutions providing care and support services for older adults were selected. Intervention group (n = 72) received 24 iCS sessions, twice a week for 12 weeks. Control group (n = 70) maintained their activities as usual. Outcomes included global cognitive function (Mini-Mental State Examination, and Alzheimer's Disease Assessment Scale-Cognitive Subscale), memory (Memory Alteration Test, and Free and Cued Selective Reminding Test), and executive functioning (Frontal Assessment Battery). All participants were assessed at baseline (T0), after the intervention (T1), and 12 weeks follow-up (T2). The results showed significant improvements in memory performance at follow-up for the intervention group and greater stability in global cognition in the intervention relative to the control group. The current iCS protocol shows effectiveness in cognitive functioning in older adults with probable AD, particularly for memory upon completion of the intervention and at follow-up, adding further support to previous iCS studies showing similar results and to the effectiveness of the current intervention.