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Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multimodal lifestyle intervention yielded cognitive and other health benefits in older adults at risk of cognitive decline. The two-year multinational randomized controlled LETHE trial evaluates the feasibility of a digitally supported, adapted FINGER intervention among at-risk older adults. Technology is used to complement in-person activities, streamline the intervention delivery, personalize recommendations, and collect digital biomarkers., Methods: Trial includes older adults (60-77 years) with digital readiness/experience with smart devices and increased dementia risk but without substantial cognitive impairment. Participants are enrolled at four sites (Austria, Finland, Italy, Sweden). At baseline, participants were randomized 1:1 ratio to 1) intervention i.e., structured multimodal lifestyle program (including diet, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in-person activities led by professionals are supported with an Android mobile phone application developed by the consortium (the LETHE App); or 2) control i.e., self-guided program (regular health advice; simplified App with no personalized/interactive content). All participants wear smartwatches to gather passive data (e.g., physical activity, sleep). Primary outcomes are retention, adherence, and change in validated dementia risk scores. Secondary outcomes include changes in lifestyle, cognition, stress, sleep, health-related quality of life, and health literacy. Additional outcomes (exploratory) include e.g. participant experiences and dementia-related biomarkers (Alzheimer's disease blood markers, neuroimaging). A sub-study explores the feasibility of novel interactive technology (audio glasses, social robot)., Results: Recruitment began in September 2022, and the last participant was randomized in June 2023. In total, 156 individuals were randomized (mean age 69 years, 65% women; balanced recruitment across the four sites). Vascular and lifestyle risk factors were common (e.g., 65% with hypertension, 69% with hypercholesterolemia, 39% physically inactive), indicating successful recruitment of a population with risk reduction potential. Trial will be completed by summer 2025. Retention until the first post-baseline visit at 6 months is high (n = 2 discontinued, retention 98.7%)., Conclusion: LETHE provides crucial information about the feasibility of technology and a digitally supported FINGER lifestyle program to promote brain health. Digital tools specifically designed for older adults could offer potential for large-scale, cost-effective prevention programs., Trial Registration: ClinicalTrials.gov (NCT05565170)., Competing Interests: Declarations. Ethics approval and consent to participate: The trial has been approved by ethical committees in Austria (Ethics Committee of the Medical University of Vienna, 1392/2022), Finland (Helsinki and Uusimaa Hospital District Ethical Committee, HUS/13675/2022, statement 22/2023), Italy (Regional Ethics Committee—CER Umbria, 27604/23/ESS), and Sweden (Swedish Ethical Review Authority, 2023–05110-02). All participants provided informed consent prior to enrollment. Consent for publication: Not applicable. Competing interests: HU, AG, MB, JB, BBS, RC, AD, DF, HH, SiH, TK, JeL, VL, CT, StH, FM, PM, ES, TN declare that they have no competing interests. AR and MK are Editors of Alzheimer’s Research & Therapy. MC and MP are employed by Innovation2Grow. NK is employed by Kaasa Solution GmbH. JyL is employed by and a stakeholder at Combinostics Ltd., (© 2024. The Author(s).)

Sepsis-associated encephalopathy is a common neurological complication of sepsis that is characterized by neuroinflammation, oxidative stress and apoptosis, which results in cognitive impairments in septic survivors. Despite numerous treatment options for this condition, none of them are definite. Therefore, this study aimed to investigate the impact of morin, a flavone known for its neuroprotective and anti-inflammatory effects, against lipopolysaccharides-induced sepsis-associated encephalopathy in albino mice for 7 days. Mice were divided into 4 groups: Negative control, morin, septic, and septic morin-treated mice. Sepsis was induced by a single injection of lipopolysaccharides (5 mg/kg, intraperitoneally), morin (50 mg/kg b. wt.) was given orally, starting from 5 h after sepsis induction, then daily for 4 other days. Morin ameliorated septic structural and functional alternations as manifested by improving the survival rate, the behavioral functions, in addition to preserving and protecting the brain tissue. This was accompanied with the augmentation of the total antioxidant capacity, as well as the suppression of tissue levels of the lipid peroxidation marker malondialdehyde, apoptosis (cleaved-caspase-3), glial fibrillary acidic protein, and the proinflammatory cytokine tumor necrosis factor. In conclusion, morin has a promising ameliorative effect to counteract the sepsis-associated encephalopathy via its anti-inflammatory and antioxidant effects and to prevent the associated cognitive impairments., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s).)

The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer's disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8 mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8 mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging., Competing Interests: Declarations Ethical Approval Housing conditions and experimental procedures were carried out following the institutional, national and international guidelines: Animal Care Committee from CIDEM (Havana, Cuba, National Institutes of Health Guide No. 80 − 23, 1978 and the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications 8023, 1978)). Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fibrinogen is a pivotal factor in the activation of neuroinflammation and cognitive impairment. While exercise, especifically swimming, has demonstrated cognitive benefits, the molecular protective mechanisms orchestrated by exercise in response to blood-brain barrier (BBB) leakage in diabetes remain elusive. This study systematically investigates the impact of fibrinogen on neuroinflammation and the role of exercise in diabetic rats. Diabetic rats underwent an 8-week swimming exercise regimen, and subsequent assessments included changes in interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), astroglia activation, BBB permeability, and key epithelial tight junction proteins such as zona occludins (ZO)-1, Claudin-5, and matrix metalloproteinase-9 (MMP-9). Spatial learning and memory were evaluated using the Morris water maze test and the novel object recognition test. The study revealed that exercise significantly improved cognitive function, potentially by suppressing fibrinogen levels and astroglia activation. Intriguingly, heightened fibrinogen expression markedly attenuated the protective effects of exercise on BBB integrity. Fibrinogen emerged as a potential compromise to exercise protective effect by increasing expression levels of inflammatory factors IL-1β and TNF-α. In summary, our findings elucidate that fibrinogen may contribute to the deterioration of cognition and diminish the protective effects of exercise by amplifying the neuroinflammatory process through damaged BBB in diabetes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Statins are the first-line treatment for hypercholesterolemia and play a key role in the prevention of cardiovascular disease (CVD). Current studies report mixed effects of statins on cognitive health, including harmful, neutral, and protective outcomes. However, these ongoing controversies about the potential cognitive adverse effects of statins may compromise their use in CVD prevention. Several factors may influence how statins affect cognition, including the unique cholesterol homeostasis in the brain, the limited permeability of the blood-brain barrier to lipoproteins, and the varying lipophilicity of different statins. This review examines the evidence linking statins to cognitive function and considers the effect of different dosages and treatment durations., Recent Findings: Earlier studies suggested cognitive disturbances with statins, but recent evidence does not strongly support a link between statins and cognitive impairment. In fact, observational studies suggest potential neuroprotective benefits, though biases like selection bias, confounding and reverse causation limit definitive conclusions. Two large randomized controlled trials, STAREE and PREVENTABLE, are underway, and their results are expected to address some of these gaps in the literature. Due to insufficient evidence in the current literature, well-designed randomized controlled trials are needed for a better understanding of statins' effects on cognition. More data is needed regarding statin type, dose intensity, and treatment duration, which may affect cognitive outcomes. Future studies are also needed to examine how statins may affect cognition in specific high-risk groups, such as individuals with mild cognitive impairment, diabetes, cardiovascular disease, or chronic kidney disease., (© 2024. The Author(s).)

Cocaine abuse has been strongly linked to blood-brain barrier (BBB) dysfunction, though the exact mechanism by which cocaine disrupts the BBB remains unclear. In this study, we found that cocaine treatment reduces the expression of glucose transporter 1 (GLUT1) in brain microvascular endothelial cells, a key factor in cocaine-induced brain glucose uptake, BBB leakage, and cognitive impairment. Mechanistically, our results show that cocaine upregulates miR-320a, which in turn suppresses GLUT1 expression via the beta 2-adrenergic receptor (ADRB2). Notably, the administration of adeno-associated viruses encoding full-length GLUT1 or miR-320a inhibitors to the brain microvascular endothelium significantly mitigated cocaine-induced BBB leakage and cognitive deficits. Additionally, we discovered that melatonin, a well-known neuroprotective hormone, alleviates cocaine-induced BBB disruption and cognitive impairment. This protective effect of melatonin was mediated through the upregulation of miR-320a-dependent GLUT1 expression in brain endothelial cells via MT 1 receptor-mediated inhibition of the cAMP/PKA/CREB signaling pathway. In conclusion, our findings demonstrate that cocaine downregulates brain microvascular GLUT1, leading to BBB dysfunction, and highlight melatonin as a potential therapeutic agent for treating cocaine-related complications., (© 2024 John Wiley & Sons Ltd.)

Background: Effect of education attainment and nutritional status on the development of cognitive impairment in Chinese elderly has not been reported., Objective: To investigate the role of education and nutrition in preventing cognitive impairment in the hospitalized Chinese elderly., Methods: Cognitive function was examined using the scoring system of Mini-Mental State Examination (MMSE) domains performed under instruction of Physicians of Geriatrics. Generalized linear mixed-effect regression was used for analyzing the association of demographic factors (age and gender), socioeconomic factors (education attainment and monthly income), as well as health-related factors (nutritional status, comorbidity, anxiety, and depression) and MMSE scores., Results: Total 246 hospitalized Chinese elders were enrolled into this study. Of them, 96 participants were 60-70 years old, 65 participants were 71-80 years old, and 85 of them were 81 years or older. Of the examined factors, we found that age, education attainment, and nutritional status were significantly associated with the outcome of MMSE scores, while monthly income and health condition (comorbidity, anxiety, and depression) were not significantly associated with MMSE score. Furthermore, education attainment was significantly associated with majority of the MMSE domains, including orientation, registration, attention and calculation, recall, and most of language sub-domains., Conclusion: Education attainment and nutritional status were significantly associated with MMSE scores in the hospitalized Chinese elderly. Higher education and better nutritional status are protective factors for the development of cognitive impairment in the hospitalized elderly Chinese population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Oxidative stress and mitochondrial dysfunction play critical roles in neurodegenerative diseases. Glutathione (GSH), a key brain antioxidant, helps to neutralize reactive oxygen species (ROS) and maintain redox balance. We investigated the effectiveness of L-cysteine (L-Cys) in preventing apoptosis induced by the ROS generator 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in mouse hippocampal neuronal HT22 cells, as well as alleviating memory and cognitive impairments caused by the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) in mice. DMNQ-induced apoptotic events in HT22 cells, including elevated cytosolic and mitochondrial ROS levels, DNA fragmentation, endoplasmic reticulum stress, and mitochondrial damage-mediated apoptotic pathways were dose-dependently abrogated by L-Cys (0.5-2 mM). The reduced intracellular GSH level, caused by DMNQ treatment, was restored by L-Cys cotreatment. Although L-Cys did not significantly restore GSH in the presence of BSO, it prevented DMNQ-induced ROS elevation, mitochondrial damage, and apoptosis. Furthermore, compared to N-acetylcysteine and GSH, L-Cys had higher 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical-scavenging activity. L-Cys also restored mitochondrial respiration capacity in DMNQ-treated HT22 cells by reversing mitochondrial fission-fusion dynamic balance. BSO administration (500 mg/kg/day) in mice led to neuronal deficits, including memory and cognitive impairments, which were effectively mitigated by oral L-Cys (15 or 30 mg/kg/day). L-Cys also reduced BSO-induced ROS levels in the mice hippocampus and cortex. These findings suggest that even though it does not contribute to intracellular GSH synthesis, exogenous L-Cys protects neuronal cells against oxidative stress-induced mitochondrial damage and apoptosis, by acting as a ROS scavenger, which is beneficial in ameliorating neurocognitive deficits caused by oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest relevant to this study., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mild Cognitive Impairment (MCI) and dementia are becoming more common with an aging population, and the numbers are expected to rise. These conditions can have a significant impact on patients, family, and health care systems. Lifestyle changes including physical activity, nutrition, quality sleep, socialization, cognitive activity and mental stimulation, routine medical care, and mental health care have the potential to prevent cognitive and functional decline and optimize daily living in all individuals, including those with MCI and early neurodegenerative disease. Brain Boosters is an important group intervention used to provide psychoeducation on lifestyle factors and strategies that can improve brain health, cognition, and functioning., Competing Interests: Disclosure The authors have nothing to disclose., (Published by Elsevier Inc.)

Introduction: The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side effects was assessed., Methods: Cognitively unimpaired 60- to 75-year-old apolipoprotein E (APOE) ε4 homozygotes and heterozygotes (the latter with elevated brain amyloid deposition) (n = 1556) received umibecestat (50 or 15 mg daily) or placebo for 7 months on average and were followed for a median (interquartile range) of 4 (3 to 6) months after washout., Results: Compared to placebo, umibecestat-treated participants had small, non-progressive, but statistically significant decline in performance on certain cognitive batteries including Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and API Preclinical Composite Cognitive test, but not Clinical Dementia Rating-Sum of Boxes. RBANS differences were no longer significant at the end of follow-up., Discussion: In people at genetic risk for AD, high-dose beta-site amyloid precursor protein cleaving enzyme (BACE) inhibition was associated with early mild cognitive worsening, which reversed shortly after washout, suggesting a symptomatic side effect not associated with neurodegeneration. Fully anonymized data, images, and samples are available upon request for further research on BACE inhibition., Highlights: This is the first trial with blinded assessment of reversibility of BACE inhibitor side effects. Umibecestat was tested in cognitively unimpaired persons at genetic risk for AD. Umibecestat led to early mild cognitive decline that reversed shortly after washout. This suggests a potentially manageable effect not associated with neurodegeneration. Further research may determine the future of BACE inhibition in AD prevention., (© 2024 Novartis Pharma AG. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

High salt (HS) intake induces hypertension and cognitive impairment. Preventive strategies include against dietary supplements. Soybean lecithin is a widely used phospholipid supplement. Lysolecithin is important in cell signaling, digestion, and absorption. This study aimed to investigate the effects of lysophosphatidylcholine containing >70% of the total phospholipids (LPC70), on hypertension and cognitive impairment induced in mice by HS intake. Mice were provided with HS solution (2% NaCl in drinking water) with or without LPC70 for 12 weeks. Blood pressure, cognitive function, and inflammatory response of intestine were determined. Hypertension and impaired object recognition memory induced by HS intake were implicated with increased inducible nitric oxide synthase in the small intestine and tau hyperphosphorylation in the prefrontal cortex. LPC70 treatment prevented cognitive impairment by suppressing inducible nitric oxide synthase and tau hyperphosphorylation. LPC70 may be valuable as a functional food component in preventing HS-induced cognitive impairment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kazuhiro Kagotani, Yuki Fujimoto, Akihito Hayashi and Ryoji Sono are employees of the Tsuji Oil Mills Corporation, an oil company. Takehiko Tsuji is the CEO of the Tsuji Oil Mills Corporation. Kuniaki Saito reports financial support and equipment, drugs, or supplies were provided by Tsuji Oil Mills Corporation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity., Methods: In vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24 hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7-P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively., Results: Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine., Conclusion: This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities., (© 2024 The Author(s). International Journal of Developmental Neuroscience published by Wiley Periodicals LLC on behalf of International Society for Developmental Neuroscience.)

Aim: To evaluate the effectiveness and safety of nutritional interventions (i.e. nutritional support, dietary patterns and dietary supplements) on cognitive function in cancer survivors., Design: Systematic review., Methods: A systematic and comprehensive search of PubMed, Web of Science, the Cochrane Library, Embase, and CINAHL was conducted from the inception until March 10, 2023. The last search was conducted on December 10, 2023., Reporting Method: PRISMA., Results: A total of 59 randomized controlled trials were included for analysis. Nutritional support, dietary patterns and dietary supplements improved cognitive function in cancer survivors with no apparent safety concerns. The anti-inflammatory diet, the fasting-mimicking diet and the web-based diet significantly improved cognitive function. Whereas the ketogenic diet or dietary advice to consume more soluble dietary fibres and less insoluble dietary fibres and lactose could not. There was evidence from dietary supplements to support the beneficial effects of polyunsaturated fatty acid supplements, traditional herbal medicines and other supplements., Conclusions: Nutritional interventions have great promise for improving cognitive function in adult cancer survivors. Further validation of the nutritional interventions supported in this study in other survivors and exploration of more effective nutritional interventions are needed., Implications for the Profession And/or Patient Care: This work can support the construction of nutritional support interventions and dietary guidance programs to prevent cancer-related cognitive decline., Impact: This work filled a gap in preventive strategies for cancer-related cognitive decline from a nutritional perspective. Nutritional support, dietary patterns, and dietary supplements can prevent cancer-related cognitive decline without serious safety concerns. This work highlighted nutritional interventions that have the potential to improve cognitive function in cancer survivors, benefiting the further construction of evidence-based nutritional intervention programs., Protocol Registration: PROSPERO., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Background: With the aging process in China showing an accelerated trend, cognitive decline and impairment have become a major issue in older people. Dietary choline supplement may be a changeable lifestyle to improve this situation., Method: We analyzed 7659 adults aged over 55 in the China Health and Nutrition Survey (CHNS), evaluated cognitive function by the global cognition score, and found the association between cognitive function and dietary intake of total choline or L-alpha-glycerylphosphorylcholine (GPC). Linear and logistic mixed models with three levels were applied to analyze the association between dietary total choline/GPC intake and global cognition score, and the risk of poor cognition., Results: The average dietary intake at baseline was 178.8 mg/d for total choline, and 16.3 mg/d for GPC. After an average follow up of 6.8 years, we found that higher intake of total choline (β = 0.083, 95%CI: 0.046,0.119, p < 0.001) and GPC (β = 0.073, 95%CI: 0.034-0.111, p < 0.001) had positively associated with global cognitive scores. Additionally, higher intake of total choline had a better effect on improving the cognitive function of women (β = 0.092, 95%CI: 0.042-0.142, p < 0.01) and individuals between 55-65 years old (β = 0.089, 95%CI: 0.046-0.132, p < 0.01). However, higher GPC intake had a better effect on the cognitive function of men (β = 0.080, 95%CI: 0.020-0.141, p < 0.05). Higher total choline intake had a protective factor against poor cognition (OR = 0.762, 95%CI: 0.676,0.860, p < 0.001); the protective effect was more pronounced for women (OR = 0.750, 95%CI: 0.639,0.879, p < 0.001) and individuals aged 55-65 (OR = 0.734, 95%CI: 0.636-0.848, p < 0.001)., Conclusions: higher dietary choline and GPC intake were beneficial for cognitive function, although we found that higher dietary choline was more effective in improving global cognitive scores at older ages; dietary choline should be supplemented as early as possible in old age to prevent poor cognition.

Diabetes, a chronic metabolic disease, affects approximately 422 million people and leads to 1.5 million deaths every year, It is found that 45% of individuals with diabetes eventually develop cognitive impairment. Here we study effects of Vitamin K2 on diabetes-associated cognitive decline (DACD) and its underlying mechanism. Diabetes was induced in adult Swiss albino mice with high-fat diet and a low dose (35 mg/kg) of streptozotocin and measured by fasting glucose and HbA1c levels. After one week of development of diabetes, one group of animals received Vitamin K2 (100 µg/kg) via oral gavage for 21 days. Then different behavioural studies, including the elevated plus maze, Morris water maze, passive avoidance test and novel object recognition test were performed followed by biochemical tests including AchE, different oxidative stress parameters (SOD, GSH, MDA, catalase, SIRT1, NRF2), inflammatory markers (TNFα, IL1β, MCP1, NFκB), apoptosis marker (Caspase 3). Hippocampal neuronal density was measured using histopathology. Vitamin K2 treatment in diabetic animals led to reduced fasting glucose and HbA1c, It could partially reverse DACD as shown by behavioural studies. Vitamin K2 adminstration reduced corticohippocampal AchE level and neuroinflammation (TNFα, IL1β, MCP1, NFκB, SIRT1). It reduced oxidative stress by increasing antioxidant enzymes (SOD, GSH, catalase), transcription factor NRF2 while reducing caspase 3. This eventually increased CA1 and CA3 neuronal density in diabetic animals. Vitamin K2 partially reverses DACD by increasing ACh while reducing the oxidative stress via Nrf2/ARE pathway and neuroinflammation, thus protecting the hippocampal neurons from diabetes associated damage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/Objectives: Impaired cognition is a key trait of the diseases of aging and is an important quality of life factor for older adults and their families. Over the past decade, there has been an increasing appreciation for the role of the microbiome in cognition, as well as emerging evidence that probiotics, such as those in yogurt and other dairy products, can have a positive impact on cognitive function. However, it is unclear to what extent the consumption of yogurt is associated with improved cognitive function in older adults. Methods: Therefore, we compared the scores for the Wechsler Adult Intelligence Scale, Digit-Symbol Substitution Test between respondents who self-reported daily yogurt/dairy consumption with those who claimed they did not in an NHANES. Results: We found that cognitive scores were significantly higher (40.03 ± 0.64 vs. 36.28 ± 1.26, p = 0.017) in respondents reporting daily yogurt/dairy consumption, though only a trend remained after adjusting for sociodemographic covariates ( p = 0.074). Conclusions: Further studies are required to confirm that this is a cause-effect relationship and whether changing diets is a low-cost means of protecting aging populations from cognitive decline and improving their quality of life.

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.

Aging represents a natural and unavoidable phenomenon in organisms. With the acceleration of population aging, investigations into aging have garnered widespread global interest. One of the most striking aspects of human aging is the decline in brain function, a phenomenon intricately tied to the onset of neurodegenerative conditions. This study aimed to assess the impact of a fish hydrolysate, rich in low-molecular-weight peptides and n-3 LC-PUFAs, on cognitive function, inflammatory response, and oxidative stress via the AGE-RAGE axis in a mouse model of accelerated aging. This model induces cognitive decline and biochemical alterations akin to those observed during natural aging. The findings revealed that fish hydrolysate exhibited a protective effect against cognitive impairment induced by D-galactose. This effect was associated with increased protein expression of SOD1 and decreased genetic expression of IL-6 and advanced glycation end products (AGE). Consequently, within the realm of preventive and personalized nutrition, fish hydrolysate emerges as a promising avenue for mitigating age-related declines in memory function., Competing Interests: Céline Lucas, Véronique Pallet, Corinne Joffre and Anne-Laure Dinel report no disclosures. Abyss Ingredients funds Camille Mougin, Mathilde Chataigner, and Elodie Bouvret. Mathilde Chataigner: employee of Abyss Ingredients; Elodie Bouvret: employee of Abyss Ingredients. This work is part of a collaborative project named Optimyss which has been funded by the National Agency of Research (ANR France) and Abyss Ingredients in the context of national French project “Plan de relance”. Mathilde Chataigner and Elodie Bouvret work for Abyss Ingredients and provide the fish hydrolysate, described in the patent number FR3099339(B1) in which Mathilde Chataigner is cited as an inventor; Camile Mougin was recruited for this specific research program by NutriNeuro. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mougin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This systematic literature review aims to answer the question of how micronutrients might influence the development and progression of dementia. In the present work, we focused on an overview of an updated review of relevant literature published in the last two decades. This review aims to delineate the relationship between micronutrient supplementation and cognitive decline in older subjects. In carrying out this review, we followed PRISMA, and our literature search was performed on PubMed. This systematic review includes only primary studies that have investigated the efficacy of nutritional interventions for the prevention of dementia and improvement of cognitive function in subjects aged 65 years or older with normal cognition, mild cognitive impairment (MCI), or Alzheimer's disease (AD). A gross heterogeneity of studies forbids the possibility of a direct comparison of the results. A review of the inclusion criteria and restrictions has been conducted to check the validity and reliability of the results. In this review, thirty-three primary studies were included. Results have shown that supplementation with vitamin D, probiotics, and PUFAs would most likely reduce cognitive decline, dementia, or AD compared with vitamins A, B, C, and E, which were seen to be relatively ineffective. Of note, when considering vitamin B supplementation, positive effects were only observed in non-aspirin users having high ω-3 fatty acid (ω-3 FA) plasma levels. In some cases, however, there were genotypic differences in subjects in response to vitamin B supplementation.

Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4-5 months of age, and became impaired at 12-18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4-5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction., (© 2024. The Author(s).)

Background: The aging population is associated with a net increase in the incidence and prevalence of chronic-degenerative diseases, particularly neurocognitive disorders. Therefore, the identification of preventative strategies to restrain the burden of such chronic conditions is of key relevance. Red wine and its components have accumulated evidence regarding their positive effects in terms of neurological pathologies associated with neurocognitive symptoms., Methods: Based on this background, the present narrative review aims to summarize the state-of-the-art evidence on the effects of red wine and its components on neurocognitive disorders in both preclinical and clinical settings., Results: The main findings highlight a protective effect of wine polyphenols present in red wine on dementia in different preclinical models of cognitive decline. The current translational clinical evidence remains uncertain, especially considering the risk-to-benefit ratio of alcohol consumption on brain health., Conclusions: Given the overall health risks associated with red wine consumption and consistent with the prevailing guidelines in the literature, there is insufficient evidence to support light-to-moderate red wine consumption as an effective strategy for preventing these diseases. However, the largely preclinical findings on polyphenols derived from red wine remain of significant interest in this context.

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures alongside other neurological comorbidities. Cognitive impairment is the most frequent comorbidity secondary to progressive neurologic changes in epilepsy. Sigma 1 receptors (σ1 receptors) are involved in the neuroprotection and pathophysiology of both conditions and targeting these receptors may have the potential to modulate both seizures and comorbidities. The current research demonstrated the effect of clemastine (10 mg/kg, P.O.), a non-selective σ1 receptor agonist, on pentylenetetrazol (PTZ) (35 mg/kg, i.p., every 48 h for 14 doses)-kindling rats by acting on σ1 receptors through its anti-inflammatory/antioxidant capacity. Clemastine and phenytoin (30 mg/kg, P.O.) or their combination were given once daily. Clemastine treatment showed a significant effect on neurochemical, behavioural, and histopathological analyses through modulation of σ1 receptors. It protected the kindling animals from seizures and attenuated their cognitive impairment in the Morris water maze test by reversing the PTZ hippocampal neuroinflammation/oxidative stress state through a significant increase in inositol-requiring enzyme 1 (IRE1), x-box binding protein 1 (XBP1), along with a reduction of total reactive oxygen species (TROS) and amyloid beta protein (Aβ). The involvement of σ1 receptors in the protective effects of clemastine was confirmed by their abrogation when utilizing NE-100, a selective σ1 receptor antagonist. In light of our findings, modulating σ1 receptors emerges as a compelling therapeutic strategy for epilepsy and its associated cognitive impairments. The significant neuroprotective effects observed with clemastine underscore the potential of σ1 receptor-targeted treatments to address both the primary symptoms and comorbidities of neurological disorders., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas., (© 2024. The Author(s).)

Computerized training platforms could be an accessible means for older adults to maintain cognitive health, and several such tools are already commercially available. However, it remains unclear whether older adults use these tools if training is not externally prescribed. We explored older adults' self-initiated experiences with cognitive training. We conducted semi-structured interviews with 13 community-dwelling adults aged 58-85 years, comprising university retirees ( N  = 8) and public housing residents ( N  = 5). Interviews were analyzed by thematic analysis. No participants voluntarily used cognitive training, and those who had done so previously reported negative experiences. Several factors shaped older adults' engagement with cognitive training, especially a preference for stimulating activities that are organic and inherently enjoyable. We reveal a mismatch between older adults' priorities and the interventions currently available and uncover issues of access and interest among low-income and minority individuals. We suggest ways to better align future interventions with older adults' priorities.

Background: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment., Methods: We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models., Results: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (β: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (β: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (β: 0.33; 95%CI: 0.12 to 0.52; P = 0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years., Conclusions: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and there is still no specific drug available to treat cognitive deficits in survivors. Vanillic acid (VA), a bioactive phenolic compound, has shown protective effects in various models of neurodegeneration; however, its impact on TBI outcomes remains elusive. Therefore, this study aimed to elucidate the possible role of VA in ameliorating TBI-induced cognitive decline and to reveal the mechanisms involved. TBI was induced using the Marmarou impact acceleration model to deliver an impact force of 300 g, and treatment with VA (50 mg/kg; P.O.) was initiated 30 minutes post-TBI. The cognitive performance, hippocampal long-term potentiation (LTP), oxidative stress markers, neurological function, cerebral edema, and morphological changes were assessed at scheduled points in time. TBI resulted in cognitive decline in the passive avoidance task, impaired LTP in the perforant path-dentate gyrus (PP-DG) pathway, increased hippocampal oxidative stress, cerebral edema, neurological deficits, and neuronal loss in the rat hippocampus. In contrast, acute VA administration mitigated all the aforementioned TBI outcomes. The data suggest that reducing synaptic plasticity impairment, regulating oxidative and antioxidant defense, alleviating cerebral edema, and preventing neuronal loss by VA can be at least partially attributed to its protection against TBI-induced cognitive decline., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

There are currently 1.8 million people in Germany affected by dementia. Despite advances in research and new treatments, there is no cure for most cases of dementia. The evidence regarding the prevention of cognitive decline in old age is unclear. In addition to the optimized adjustment of drug treatment (e.g., arterial hypertension and diabetes mellitus), preventive measures that can be influenced by individuals themselves play an important role. These include areas such as physical and cognitive activity, remedying hearing loss, sleep, social contacts, abstaining from alcohol as well as tobacco consumption and nutrition. Multimodal concepts and digital approaches appear to be promising and an increase in evidence is expected in the coming years., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aging is a primary risk factor for cognitive impairment and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing, insulin signaling, and histone deacetylation activity. Therefore, a pharmaceutical intervention of aging that targets distinct but overlapping pathways provides a basis for testing combinations of drugs as a cocktail. Our previous study showed that middle-aged mice treated with a cocktail of rapamycin, acarbose, and phenylbutyrate for 3 months had increased resilience to age-related cognitive decline. This finding provided the rationale to investigate the transcriptomic and molecular changes within the brains of mice that received this cocktail treatment or control treatment. Transcriptomic profiles were generated through ribonucleic acid (RNA) sequencing, and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured using immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or control. Results showed that biological processes that enhance aging were suppressed, with an increased trend of autophagy in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways., (© 2024. The Author(s).)

Luteolin is an essential natural polyphenol found in a variety of plants. Numerous studies have supported its protective role in neurodegenerative diseases, yet the research for its therapeutic utility in D-galactose (D-gal)-induced brain ageing is still lacking. In this study, the potential neuroprotective impact of luteolin against D-gal-induced brain ageing was explored. Forty rats were randomly divided into four groups: control, luteolin, D-gal, and luteolin-administered D-gal groups. All groups were subjected to behavioural, cholinergic function, and hippocampal mitochondrial respiration assessments. Hippocampal oxidative, neuro-inflammatory, senescence and apoptotic indicators were detected. Gene expressions of SIRT1, BDNF, and RAGE were assessed. Hippocampal histopathological studies, along with GFAP and Ki67 immunoreactivity, were performed. Our results demonstrated that luteolin effectively alleviated D-gal-induced cognitive impairment and reversed cholinergic abnormalities. Furthermore, luteolin administration substantially mitigated hippocampus oxidative stress, mitochondrial dysfunction, neuro-inflammation, and senescence triggered by D-gal. Additionally, luteolin treatment considerably attenuated neuronal apoptosis and upregulated hippocampal SIRT1 mRNA expression. In conclusion, our findings revealed that luteolin administration attenuated D-gal-evoked brain senescence, improving mitochondrial function and enhancing hippocampal neuroregeneration in an ageing rat model through its antioxidant, senolytic, anti-inflammatory, and anti-apoptotic impacts, possibly due to upregulation of SIRT1. Luteolin could be a promising therapeutic modality for brain aging-associated abnormalities., (© 2024. The Author(s).)

Background: Major Depressive Disorder (MDD) affects 350 million people worldwide. Electroconvulsive therapy (ECT) is effective, yet research on cognitive assessments post-treatment is lacking. This study systematically reviews and meta-analyzes the effectiveness of cognitive assessment tools post-ECT to optimize MDD treatment., Methods: Following PRISMA guidelines, this review was pre-registered on PROSPERO (CRD42023470318). Searches were conducted across nine databases up to November 12, 2023. Quality assessment for Randomized Controlled Trials (RCTs) and quasi-experimental studies was performed using the Cochrane risk of bias tool, JBI critical appraisal tools, and the Jadad scale. Meta-analyses for short-term and long-term cognitive function involved 24 and 18 tools, respectively., Findings: Thirty studies (20 RCTs and 10 quasi-experimental) involving 2462 MDD patients were evaluated. Results indicated no significant differences in overall short-term and long-term cognitive functions post-ECT. Short-term analysis showed impairments in memory, learning, and verbal abilities but improvements in attention and processing speed. Long-term analysis revealed enhancements in memory, learning, verbal, and visuospatial abilities compared to baseline. Based on GRADE classification, we recommend 11 tools for assessing acute cognitive function and 10 tools for chronic cognitive impairment. These tools demonstrated high reliability and validity, supporting their clinical use., Interpretation: These findings provide critical evidence for future ECT clinical guidelines in managing MDD. The recommended tools can aid clinicians in adjusting ECT regimens, identifying early cognitive changes, and improving therapeutic outcomes in MDD treatment., Competing Interests: Declaration of Competing Interest All other authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Underwater exercise is becoming increasingly prevalent, during which brain function is necessary but is also at risk. However, no study has explored how prolonged exercise affect the brain in underwater environment. Previous studies have indicated that excessive exercise in common environment causes brain dysfunction but have failed to provide appropriate interventions. Numerous evidence has indicated the neuroprotective effect of hyperbaric oxygen preconditioning (HBO-PC). The objective of this study was to investigate the cognitive effect of prolonged underwater exercise (PUE) and to explore the potential neuroprotective effect of HBO-PC in underwater environment. Rats swimming for 3 h in a simulated hyperbaric chamber (2.0 ATA) was used to establish the PUE animal model and HBO-PC (2.5 ATA for 1, 3,5 times respectively) was administrated before PUE. The results demonstrated that PUE triggers anxiety-like behaviors, cognitive impairment accompanied by hippocampal dysfunction, microglia activation and neuroinflammation. Conversely, 3 HBO-PC rescued anxiety-like behaviors and cognitive impairment. Mechanistically, 3 HBO-PC reduced microglia activation and switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. These findings illustrated that PUE induces anxiety-like behaviors and cognitive impairment and HBO-PC of proper frequency may provide an appropriate and less invasive intervention for protecting the brain in underwater exercise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats., Methods: Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting., Results: The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group., Conclusion: In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus., (© 2024. The Author(s).)

The EAT-Lancet Commission proposed a planetary health diet to improve human health within planetary boundaries; however, little is known about the association between adherence to this diet and cognitive decline. We used data from three waves of the Brazilian Longitudinal Study of Adult Health to evaluate the association between the planetary health diet and cognitive decline using linear mixed-effects models. Here we show that in 11,737 participants (mean (s.d.) age 51.6 (9.0) years, 54% women and 53% white), higher adherence to the planetary health diet was associated with slower memory decline (P = 0.046) and that income was a modifier in this association (P < 0.001). Adherence to the planetary health diet was associated with slower decline of memory (P = 0.040) and global cognition (P = 0.009) in high-income participants. No association was found among low-income participants. The results of our study highlight that the promotion of healthy dietary patterns should take into consideration income barriers as well as differences in dietary habits to achieve high adherence., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Diabetic cognitive dysfunction (DCD) refers to cognitive impairment in individuals with diabetes, which is one of the most important comorbidities and complications. Preliminary evidence suggests that consuming sufficient dietary fiber could have benefits for both diabetes and cognitive function. However, the effect and underlying mechanism of dietary fiber on DCD remain unclear. We conducted a cross-sectional analysis using data from NHANES involving 2072 diabetics and indicated a significant positive dose-response relationship between the dietary fiber intake and cognitive performance in diabetics. Furthermore, we observed disrupted cognitive function and neuronal morphology in high-fat diet induced DCD mice, both of which were effectively restored by fucoidan supplementation through alleviating DNA epigenetic metabolic disorders. Moreover, fucoidan supplementation enhanced the levels of short-chain fatty acids (SCFAs) in the cecum of diabetic mice. These SCFAs enhanced TET2 protein stability by activating phosphorylated AMPK and improved TETs activity by reducing the ratio of (succinic acid + fumaric acid)/ α-ketoglutaric acid, subsequently enhancing TET2 function. The positive correlation between dietary fiber intake and cognitive function in diabetics was supported by human and animal studies alike. Importantly, fucoidan can prevent the occurrence of DCD by promoting TET2-mediated active DNA demethylation in the cerebral cortex of diabetic mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the central nervous system, oligodendrocytes wrap around neuronal axons to form myelin, an insulating layer or sheath that allows for the efficient conductance of action potentials. In addition to structural insulation, myelin provides encased axons with nutrient, metabolic and defensive support. Demyelination, or myelin loss, can therefore cause axonal dysfunction, leading to neurological impairment and disease. In Alzheimer's disease (AD), progressive white matter demyelination is acknowledged as one of the earliest pathologies preceding symptom onset. Unfortunately, current pharmacotherapy for slowing demyelination or promoting remyelination in AD is nonexistent. Exercise is recognized for its wide-ranging benefits to human health, including improved mental health and the prevention of lifestyle-related diseases. Mounting evidence suggests the contribution of physical activity in delaying the progression of dementia in elderly populations. Recent mechanistic studies have shown that exercise facilitates myelination in the brain through the vitalization of intrinsic pro-myelination cues, such as increased neurotrophic factors and electrical activity. In this review, we summarize and discuss the potential of physical exercise on counteracting aging-associated white matter demyelination, which causes cognitive decline in AD. We highlight the need of further basic and clinical research investigations on this topic to establish novel approaches for healthy and improved brain aging.

Background & Aims: Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain., Methods: Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis., Results: RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways., Conclusions: Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements., Competing Interests: Conflict of interest K.S. was employed by AnalytiCon Discovery GmbH, Potsdam, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors have approved the manuscript in its final form., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Stroke and vascular cognitive impairment (VCI) are major global public health pandemics. The increased incidence of stroke and VCI is in part due to modifiable risk factors (MRFs), with hypertension (HTN) being the strongest single MRF. Even though the underlying causes of HTN are multifactorial, lifestyle choices (eg, poor diet, physical inactivity, alcohol consumption) are chief contributors. Lifestyle medicine (LSM) is a medical and evidence-based discipline that is a promising approach for preventing stroke and cognitive impairment, including VCI. The empirical evidence from systematic reviews, meta-analyses and large population-based studies has reported on the effectiveness of LSM interventions. However, the evaluation of such complex, social and behavioural interventions warrants more information to allow its successful implementation into innovative clinical care models. More importantly, we need to understand how such interventions work, who it works for and under what circumstances to successfully manage HTN and other MRFs (eg, hyperlipidaemia, smoking, alcohol use and diet)., Methods and Analysis: This realist review will follow the Realist and Meta-narrative Evidence Synthesis: Evolving Standards. The review will comprise four stages: (1) clarify the scope, (2) search for the evidence, (3) critically appraise primary studies and extract data focusing on the context, mechanism and outcome configuration and (4) synthesise evidence and draw conclusions., Ethics and Dissemination: Research ethics board approval is not required for this review. The primary output of this review will be an evidence-based programme theory for LSM interventions for the management of HTN and other MRFs to reduce the risk of stroke and VCI. Findings from this review will be disseminated at three levels: micro (eg, patients, caregivers, clinicians, non-research partners), meso (eg, public, national not-for-profit organisations, professional associations and centres) and macro (eg, policymakers and government partners)., Prospero Registration Number: CRD42024511566., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Neurodegenerative diseases, which are characterized by progressive neuronal loss and cognitive decline, are a significant concern for the aging population. Neuroinflammation, a shared characteristic of these diseases, is implicated in their pathogenesis. This article briefly summarizes the role of magnesium, an essential mineral involved in numerous enzymatic reactions and critical for neuronal bioactivity, in the context of neuroinflammation and cognitive decline. The potential neuroprotective effects of magnesium, including the mechanisms of neuroprotection by magnesium through maintaining neuronal ion homeostasis, reducing inflammation, and preventing excitotoxicity, are also described. Additionally, we discuss the impact of inadequate magnesium on neuroinflammation and its potential as a therapeutic agent for attenuating cognitive decline to improve neurodegenerative conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Patel, Akimbekov, Grant, Dean, Fang and Razzaque.)

Objective: To explore the correlation between different types of vegetable and fruit intake and cognitive function among the older adults in Chongqing, China, and to provide a scientific basis for developing efficient lifestyle interventions for the prevention of Mild Cognitive Impairment (MCI)., Method: Approximately 728 older adults in urban and rural areas of Chongqing were surveyed using face-to-face questionnaires. Cognitive function was assessed with the Montreal Cognitive Assessment-Basic (MoCA-B) scale, and the vegetable and fruit intake groups were investigated with the Simple Food Frequency Counting Survey Scale. Binary logistic regression was used to explore the effect of the vegetable and fruit intake group on cognitive function. Subgroup analysis was used to demonstrate the robustness of the results., Result: Of the 728 participants in the study, 36.40% were likely to have MCI, which is higher than the national average for this condition. After adjusting for confounders, compared to the Q1 group, fruit and root vegetable intake was a protective factor for MCI, showing a dose-response relationship ( p < 0.05). Only lower intake (Q2) of total vegetables, medium intake (Q2, Q3) of solanaceous vegetables, and medium-high intake (Q2, Q4) of fungi and algae was protective against MCI, whereas the leafy vegetables showed no relation to MCI. Apart from this, participants who were older, female, unmarried, non-smoking, and engaged in physical labor, and who had an average monthly income of less than 3000 RMB were more likely to suffer from cognitive impairment., Conclusion: This suggested that the fruit-intake groups and some vegetable-intake groups showed a protective effect on cognitive function, and might behave differently depending on their different intake and demographic characteristics. A sensible, healthy diet can help prevent MCI.

Functional oligosaccharides induce specific alterations in gut microbiota, potentially providing physiological benefits. However, the effects of laminaripentaose (LPA) on metabolic syndrome and the mechanism underlying it have not been intensively investigated yet. This study aimed to determine the effects of LPA on obesity and obesity-induced cognition impairment in mice. C57BL/6N mice fed with a high-fat diet received an LPA treatment for 12 weeks. An antibiotic intervention was further applied to evaluate the effects of the gut microbiota on cognitive functions. LPA treatment (500 mg/kg) reduced the weight gain by 32.4%. Furthermore, LPA improved memory functions and reduced hippocampal insulin resistance and neuronal injury. LPA markedly reduced systemic low-grade inflammation and intestinal barrier injury. Moreover, LPA increased gut beneficial bacteria, and Butyricimonas and Bifidobacterium were increased by 94.0 and 422.7%, respectively, accompanied by increased fecal short-chain fatty acids. Interestingly, antibiotic cocktail treatment abrogated the beneficial effects of LPA on cognition, which further suggests that LPA may attenuate obesity-induced cognition impairment via the gut-brain axis. Our findings provide the first evidence for the potential of dietary LPA to prevent obesity and obesity-associated complications.

Rice protein peptide (RPP) has been reported to alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis, but its potential protective effect and fundamental neurobiological mechanisms against DSS-induced inflammatory bowel disease (IBD), coupled with depression and cognitive impairment, remain unclear. In this study, RPP treatment in DSS-induced mice inhibited decreases in body weight and colon length and improved intestinal barrier function and behavioral performance. RPP treatment enhanced phenylalanine and tyrosine metabolism in the brains of mice, and it upregulated metabolites such as l-dopa, phenylethylamine, and 3,4-dihydroxyphenylacetate. Additionally, RPP treatment enhanced the brain-derived neurotrophic factor (BDNF) by upregulating the BDNF/TrkB/CREB signaling pathway. Spearman's correlation analysis revealed that the phenylalanine and tyrosine contents in the brain were significantly negatively correlated with the BDNF/TrkB/CREB signaling pathway and behavioral performance. In conclusion, this study suggested that RPP may serve as a unique nutritional strategy for preventing IBD and its associated cognitive impairment and depression symptoms.

Introduction: Promising evidence is emerging for the procognitive, anti-inflammatory and neuroprotective properties of dietary flavonoids, particularly anthocyanins that provide red, purple and blue plant pigments., Methods and Analysis: The 'Food for Thought' study is a multicentre, 6-month randomised, parallel 3-arm clinical trial. Its primary aim is to investigate whether anthocyanin consumption, either through diet or supplementation, can prevent memory loss progression and improve inflammatory and cardiovascular health in older adults at risk for dementia. Eligible participants will include those aged 60-85 years with a diagnosis of amnestic mild cognitive impairment or with a self-referral of memory concerns and scoring ≤13 on the Memory Index Score within the Telephone Montreal Cognitive Assessment screening test. Participants will be randomised to one of three arms: High anthocyanin ('purple foods') diet (aiming for a target of 250 mg anthocyanins/day); freeze-dried product derived from blackcurrants (250 mg anthocyanins/day); or control (coloured maltose powder). The primary outcome is auditory anterograde memory functioning assessed by the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall. Secondary outcomes are additional cognitive functions including processing speed, working memory, aspects of executive functioning (attentional shifting and word generativity) and premorbid estimate as well as subjective memory problems and self-reported depression symptoms. Additional secondary outcomes are blood pressure, inflammatory biomarkers, brain-derived neurotrophic factor, fatty acid profile, apolipoprotein E and polyphenol metabolites, gut microbiota composition and function and vascular and microvascular endothelial function tests. Repeated measures analysis of variance and/or mixed linear modelling will evaluate changes over time, with the inclusion of covariates., Ethics and Dissemination: Ethics approval has been obtained from the Greater Western Human Research Ethics Committee (2021/ETH12083). A Consumer Advisory Group was established to guide and review the protocol and dissemination strategy. The results of this trial are intended to be published in a peer-reviewed journal., Trial Sponsor: National Health and Medical Research Centre Dementia Collaborative Research Centre.Start date of clinical trial: 02 September 2022.Expected end date: 11 October 2024., Trial Registration Number: ACTRN12622000065796., Competing Interests: Competing interests: HB is or has been an advisory board member or consultant to Biogen, Eisai, Eli Lilly, Medicines Australia, Roche and Skin2Neuron. He is a Medical/Clinical Advisory Board member for Montefiore Homes and Cranbrook Care. There are no other conflicts of interest among the other authors., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The progressive form of Alzheimer's disease (AD) is a neurological condition marked by decline in older people's memory and cognition. Scopolamine is a behavioral technique that is frequently used to study cognitive disorders, such as Alzheimer's disease. This investigation aimed to determine the protective effects of ethanolic extracts derived from Sterculia guttata (ESG) on neurological & pathological changes induced by Scopolamine in rats with Alzheimer's. The ESG procured through a 48-hour hot maceration, followed by column chromatography, isolation and characterization using techniques such as FTIR, 1HNMR, 13CNMR and mass spectra. A flavonoid called Diosmin was identified in the extract. Rats were segregated into five groups: normal, scopolamine, scopolamine + Donepezil, scopolamine + ESG (200mg per kg orally), & scopolamine + ESG (400mg per kg orally) for a study of 14 day duration. Memory & learning abilities were assessed using the rectangular maze and Cook's pole climbing model. Additionally, biochemical parameters and brain histology were analyzed. ESG treatment mitigated scopolamine-induced changes in acetylcholinesterase, dopamine, serotonin, glutamate, and GABA levels, suggesting neuroprotection. These findings propose that ethanolic extracts of Sterculia guttata (ESG) show promise as effective preventive or therapeutic agents due to their potential for neuroprotection & cognitive enhancement in AD.

Chronic kidney disease (CKD) is among the leading causes of morbidity and mortality as it affects more than 10% of the global adult population. Cognitive impairment has a positive correlation with the stage of CKD. It has been recorded in more than half of CKD patients undergoing kidney replacement therapy. The assessment of cognitive function in dialysis patients presents challenges due to various patient limitations. Such a common debilitating comorbidity of CKD has no approved treatment option, highlighting the importance of preventive measures and screening modalities. Erythropoietin therapy, exercise training, cognitive stimulation or behavioral therapies, alterations in dialysis frequency, dialysate cooling and kidney transplantation have been proposed as potential preventive and/or therapeutic options with variable efficiency at a clinical level. Regular screening, such as yearly, for cognitive impairment in maintenance dialysis patients is not only beneficial for timely and accurate diagnosis but also crucial for effective management and improved patient care. However, current practices face challenges, including the absence of validated tools specific for kidney failure and complications arising from patient conditions., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Recent studies have suggested that sustained multidomain interventions, including physical exercise, may be beneficial in preventing cognitive decline. This review aims to assess the impact of prolonged physical exercise and multidomain strategies on overall cognitive faculties and dementia risk among community-dwelling older adults without dementia., Methods: We systematically searched PubMed, Web of Science, PsychInfo, and CINHAL databases from inception until April 1, 2024, for randomized controlled trials that investigated the effects of long-term (≥ 12 months) physical exercise or multidomain interventions on non-demented, community-dwelling older adults. The primary outcomes assessed were changes in global cognition and the risk of mild cognitive impairment (MCI) or dementia. Standardized mean differences (SMD) and risk ratios (RR) with 95 % confidence intervals were computed using a random-effects inverse-variance method with the Hartung-Knapp-Sidik-Jonkman adjustment for effect size calculation. The Cochrane Risk-of-Bias-2 tool (RoB-2) was used for bias assessment, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was applied to evaluate the certainty of evidence., Results: Sixteen trials, including 11,402 participants (mean age 73.2 [±5.5] years; 62.3 % female) were examined. The risk of bias was low. Moderate-certainty evidence indicated that physical exercise interventions had modest to no effect on cognitive function (k= 9, SMD: 0.05; 95 % CI: -0.04-0.13; p = 0.25), whereas multidomain interventions were significantly impactful (k=7, SMD: 0.09; 95 % CI: 0.04-0.15; p < 0.01). Physical exercise interventions did not alter MCI risk (k= 4, RR: 0.98; 95 % CI: 0.73-1.31; p = 0.79) or dementia onset (k= 4, RR: 0.61; 95 % CI: 0.25-1.52; p = 0.19), with very low-to low-certainty evidence, respectively., Conclusions: Integrative multidomain strategies incorporating physical exercise may benefit the global cognitive function of older adults. However, long-term physical exercise alone did not yield any cognitive gains. The effectiveness of such exercise interventions to mitigate the overall risk of incident MCI and dementia warrants further research., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

PM2.5 exposure is a challenging environmental issue that is closely related to cognitive development impairment; however, currently, relevant means for prevention and treatment remain lacking. Herein, we determined the preventive effect of docosahexaenoic acid (DHA) supplementation on the neurodevelopmental toxicity induced by PM2.5 exposure. Neonatal rats were divided randomly into three groups: control, PM2.5, and DHA + PM2.5 groups. DHA could ameliorate PM2.5-induced learning and memory dysfunction, as well as reverse the impairment of hippocampal synaptic plasticity, evidenced by enhanced long-term potentiation, recovered synaptic ultrastructure, and increased expression of synaptic proteins. Moreover, DHA increased CREB phosphorylation and BDNF levels and attenuated neuroinflammation and oxidative stress, reflected by lower levels of IBA-1, IL-1β, and IL-6 and increased levels of SOD1 and Nrf2. In summary, our findings demonstrated that supplementation of DHA effectively mitigated the cognitive dysfunction and synaptic plasticity impairment induced by early postnatal exposure to PM2.5. These beneficial effects may be attributed to the upregulation of the CREB/BDNF signaling pathway, as well as the reduction of neuroinflammation and oxidative stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: The proportion of the elderly population is on the rise across the globe, and with it the prevalence of age-related neurodegenerative diseases. The gut microbiota, whose composition is highly regulated by dietary intake, has emerged as an exciting research field in neurology due to its pivotal role in modulating brain functions via the gut-brain axis., Objectives: We aimed at conducting a systematic review of preclinical and clinical studies investigating the effects of dietary interventions on cognitive ageing in conjunction with changes in gut microbiota composition and functionality., Methods: PubMed and Scopus were searched using terms related to ageing, cognition, gut microbiota and dietary interventions. Studies were screened, selected based on previously determined inclusion and exclusion criteria, and evaluated for methodological quality using recommended risk of bias assessment tools., Results: A total of 32 studies (18 preclinical and 14 clinical) were selected for inclusion. We found that most of the animal studies showed significant positive intervention effects on cognitive behavior, while outcomes on cognition, microbiome features, and health parameters in humans were less pronounced. The effectiveness of dietary interventions depended markedly on the age, gender, degree of cognitive decline and baseline microbiome composition of participants., Conclusion: To harness the full potential of microbiome-inspired nutrition for cognitive health, one of the main challenges remains to better understand the interplay between host, his microbiome, dietary exposures, whilst also taking into account environmental influences. Future research should aim toward making use of host-specific microbiome data to guide the development of personalized therapies.

The aim of this research was to explore the potential of treadmill exercise in preventing brain aging and neurodegenerative diseases caused by oxidative stress, by studying its effects on D-galactose-induced mice and the mechanisms involved. The results showed that C57BL/6 mice induced with D-gal exhibited cognitive impairment and oxidative stress damage, which was ameliorated by treadmill exercise. The Morris water maze also showed that exercise improved cognitive performance in aging mice and alleviated hippocampal and mitochondrial damage. The study also found that treadmill exercise increased the expression of nuclear factor Nrf2, p-GSK3β, HO-1, NQO1, BDNF, and Bcl-2 proteins while decreasing the expression of Bax. Furthermore, there was a substantial increase in the levels of CAT, GSH-PX and SOD in the serum, along with a decrease in MDA levels. The outcomes propose that aerobic exercise has the potential to hinder oxidative stress and cell death in mitochondria through the modulation of the Nrf2/GSK3β signaling pathway, thus improving cognitive impairment observed in the aging model induced by D-galactose. It appears that treadmill exercise could potentially serve as an effective therapeutic approach to mitigating brain aging and neurodegenerative diseases triggered by oxidative stress., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A helpful method to understand cognitive decline in older people is to consider this entity as increasing cognitive frailty caused by a number of interacting pathological processes. Over the last 20 years, multiple lifestyle, environmental and constitutional factors have been linked to the development of cognitive decline. For two interventions based on these factors, increasing physical activity and the control of hypertension, there is class 1 evidence for benefit. Other interventions based on these factors do not have the support of high-level evidence for the alteration of cognitive decline, but their other benefits would argue for their implementation. These interventions include increasing education, smoking cessation, avoiding head injuries, decreasing exposure to air pollution and increased social connections. As cognitive decline is experienced almost universally with ageing, and serious cognitive decline is experienced by substantial numbers of low-risk individuals, whole-of-population intervention strategies are the most effective and efficient. For other interventions to help prevent cognitive decline there is not sufficient evidence for their implementation to be recommended. These include alteration of alcohol ingestion, correction of hearing loss, treatment of depression, dietary interventions, menopausal hormone treatment and monoclonal antibodies directed against amyloid-β., Competing Interests: Declaration of competing interest The author declares that he has no competing interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Postoperative cognitive impairment (POCD) is a complication of cardiopulmonary bypass (CPB). Remimazolam is an ultra-short acting benzodiazepine that can be used for anesthesia or sedation during surgery. This study investigated the role of remimazolam in inflammasome activation and microglia polarization using CPB rat model and lipopolysaccharide (LPS)-induced microglia model. The cognitive function of rats was evaluated by Morris water maze. TUNEL assay was performed to detect apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. Reverse transcription-polymerase chain reaction was used to assess the expression of inflammasome and M1/M2-related microglia markers. Flow cytometry was performed to evaluate the expression of CD16/32 and CD206 in microglia. The results showed that remimazolam improved the memory and learning abilities in CPB rats. CPB rats and LPS-treated microglia showed increased apoptosis, pro-inflammatory cytokines level, and inflammasome expression as well as decreased microglia activation, while the results were reversed after remimazolam treatment. Besides, remimazolam treatment promoted the expression of M2-related markers in LPS-treated microglia. Nigericin treatment reversed the increased M2-related mRNA levels and the decreased apoptosis and inflammatory responses induced by remimazolam treatment. In conclusion, remimazolam attenuated POCD after CPB through regulating neuroinflammation and microglia M2 polarization, suggesting a new insight into the clinical treatment of POCD after CPB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)