Improve Brain Health Research Articles

Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Older Veterans: Protocol for a Randomized Controlled Trial.

Growing health care challenges resulting from a rapidly expanding aging population necessitate examining effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence. This work aims to implement a multimodal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise-induced adaptations to sedentary older adults' brains and behaviors. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise-induced changes to cerebral perfusion, cerebral vascular reactivity (CVR), and cognitive and sensorimotor task-dependent functional magnetic resonance imaging (fMRI) after prescribed exercise. Sedentary older adults (aged 65-80 years) were randomly assigned to either a 12-week aerobic-based interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness used the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, and cortical activation using fMRI during verbal fluency and motor tapping tasks. A battery of cognitive-executive and motor function tasks outside the scanning environment will be performed before and after the interventions. Our studies and others show that improved cardiovascular fitness in older adults results in improved outcomes related to physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI, which corresponds with improved task performance (cognitive-executive and motor). We hypothesize that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR through a greater magnitude of reactivity in brain areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To differentiate between neural and vascular adaptations in these regions, we will map changes in basal perfusion and CVR over the inferior frontal and the motor cortices-regions we have previously shown to be beneficially altered during fMRI BOLD (blood oxygen level dependent), such as verbal fluency and motor tapping, through improved cardiovascular fitness. Exercise is one of the most impactful interventions for improving physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention is supported, it would add critically important insights into the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction. ClinicalTrials.gov NCT05932069; https://clinicaltrials.gov/study/NCT05932069. DERR1-10.2196/58316.

Exploring the Impact of Cognitive Dysfunction During Recurrent Depression in a Sample of Mid-to-Older Age British South Asians: A Qualitative Study.

Depression is a major public health issue, increasing the risk of comorbidities. Some people with depression experience cognitive dysfunction, which can persist even after symptomatic recovery. British South Asians are at greater risk of developing depression and are less likely to seek treatment. It is important to understand their experience of subjective cognitive dysfunction in depression and how best to support them. This study explored subjective experience of cognitive dysfunction during recurrent depression, in a sample of 12 British South Asians aged between 45 and 60 years. We conducted semi-structured interviews to explore cognitive dysfunction during recurrent depression. We analysed the data using thematic analysis. Difficulties in attention and concentration resulted in lower quality of social relationships, including not feeling present and social isolation. Learning new information was difficult, thus impacting productivity. Participants found it difficult to engage in enjoyable activities that promoted brain health. The emotional, physical and spiritual impact negatively impacted on quality of life. Cognitive strategies used in therapies could improve brain health and functional recovery in people living with depression. Mental health nurses play a pivotal role in providing culturally appropriate information and strategies for managing cognitive dysfunction in recurrent depression.

Synergy of exercise and hypoxia for brain health and aging – A narrative review

Regular exercise is a well-established means to improve brain health and prevent age-related neurological diseases, including dementia (Marques-Aleixo et al., 2020). The precise mechanisms how direct exercise effects are transmitted to the brain remain incompletely understood. However, the increased oxygen demand and associated metabolic stress in the primarily affected tissues – the working skeletal muscle, the cardiovascular and the respiratory system – likely play crucial roles in exercise-signalling to the brain (Severinsen & Pedersen, 2020). Besides the mobilization of beneficial circulating factors, the modulation of blood properties and blood-flow, the immune system and the autonomous system are involved. Intriguingly, physiological stress induced by low environmental oxygen availability (hypoxia) can induce the activation of similar processes like exercise. The aim of this contribution is to evaluate the role of hypoxia in the benefits of exercise on the brain. Accumulating evidence demonstrates the potential of direct modulation of inspired oxygen levels to improve neurological diseases (Burtscher et al., 2021). Reduced all-cause mortality in people living at moderate altitudes (and therefore in chronic, mild hypobaric hypoxia) may also be associated with reduced risk of neurological diseases, including of stroke (Faeh et al., 2009). This is surprising, because the hypoxic stress at moderate altitudes (usually defined as altitudes between 1,500 and 2,500 m) is generally considered too low to induce substantial hypoxia adaptations. It is thus possible that the combination of moderate environmental hypoxia at moderate altitude with the increased oxygen demand during exercise is required to promote protective adaptations, such as of the brain. Considering this possibility, synergistic and complementary molecular and systemic responses and adaptations to exercise and hypoxia may benefit the brain. Among the involved molecular processes are mitochondrial changes following cellular stress that are also linked to the regulation of adaptations by the transcription factor hypoxia inducible factor, which is activated by both hypoxia and exercise. Mitochondria are the main molecular oxygen consumers, respond sensitively to stress and dispose of a wide array of intra- and intercellular communication modes (Memme et al., 2021). Moreover, exerkines, blood-borne factors released in response to exercise, have emerged as important mediators of inter-organ exercise-signalling (Severinsen & Pedersen, 2020) and modulate the autonomic and immune system in response to hypoxic and metabolic stress. In conclusion, the activation of endogenous responses to hypoxic and metabolic stress are powerful means to improve brain health and healthy aging. Based on the overlapping and distinct physiological responses to hypoxia and exercise, brain benefits of exercising at higher altitudes and advances in the development of customized strategies to improve brain resilience are promising approaches to target neurological diseases. While the safe performance of exercise in moderate altitudes is already considered an impactful way to improve brain health, the optimization of combined exercise and (artificially induced) hypoxia for specific target groups requires further in-depth investigation. References Burtscher, J., Mallet, R. T., Burtscher, M., & Millet, G. P. (2021). Hypoxia and brain aging: Neurodegeneration or neuroprotection? Ageing Research Reviews, 68, Article 101343. https://doi.org/10.1016/j.arr.2021.101343 Faeh, D., Gutzwiller, F., Bopp, M., & Group, S. N. C. S. (2009). Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation, 120(6), 495-501. https://doi.org/10.1161/CIRCULATIONAHA.108.819250 Marques-Aleixo, I., Beleza, J., Sampaio, A., Stevanović, J., Coxito, P., Gonçalves, I., Ascensão, A., & Magalhães, J. (2020). Preventive and therapeutic potential of physical exercise in neurodegenerative diseases. Antioxidants & Redox Signaling, 34(8), 674–693. https://doi.org/10.1089/ars.2020.8075 Memme, J. M., Erlich, A. T., Phukan, G., & Hood, D. A. (2021). Exercise and mitochondrial health. The Journal of Physiology, 599(3), 803-817. https://doi.org/10.1113/jp278853 Severinsen, M. C. K., & Pedersen, B. K. (2020). Muscle-organ crosstalk: The emerging roles of myokines. Endocrine Reviews, 41(4), 594-609. https://doi.org/10.1210/endrev/bnaa016

Evaluation of the clinical efficacy of Pediococcus acidilactici CCFM6432 in alleviating depression

Aim: Accumulating evidence highlights the crucial role of the “gut-brain axis” and emphasizes the potential of dietary interventions to improve brain health through this pathway. This study assesses the effects of the probiotic Pediococcus acidilactici CCFM6432 on mood, sleep, and gastrointestinal function in patients with depressive disorder. Methods: This clinical trial is a randomized, placebo-controlled study (Registration: ChiCTR2300071025). It enrolled 39 adult patients diagnosed with depressive disorder, who were randomly assigned to either the placebo control group (n = 19) or the CCFM6432 intervention group (n = 20). The intervention period spanned four weeks. Assessments were conducted at both the beginning and end of the trial, including comprehensive questionnaire evaluations and the collection of serum and fecal samples. Results: In comparison to the placebo, treatment with CCFM6432 significantly decreased depression and anxiety scores, as well as ameliorated gastrointestinal dysfunction and poor sleep quality commonly associated with mood disorders. Microbiota analysis revealed an increase in species richness without notable changes in overall diversity, yet Pediococcus species was found to be more abundant post-treatment. Functional analysis indicated reduced activity in the NOD-like receptor signaling pathway, suggesting anti-inflammatory effects induced by the probiotic. Metabolomic profiling identified elevated levels of fecal lactic acid, which correlated with lower Hospital Anxiety and Depression Scale (HADS) scores, thereby linking probiotic metabolism to mood enhancement. Conclusion: These findings imply that CCFM6432 may improve brain function by modulating gut microbiota and their mediated immune homeostasis, underscoring its potential as an adjunctive treatment for mental disorders.

Acute exercise alters brain glucose metabolism in aging and Alzheimer's disease.

There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial 'AEROBIC' (NCT04299308) enrolled 60 older adults who were cognitively healthy (n=30) or cognitively impaired (n=30) to characterize the acute brain responses to moderate [45-55% heart rate reserve (HRR)] and higher (65-75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG-PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG-PET standardized uptake value ratio (SUVR) differed between exercise (1.045±0.082) and rest (0.985±0.077) across subjects [Diff=-0.060, t(58)=13.8, P<0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56)=161.99, P<0.001] more in the higher intensity group [mean difference (MD)=97.0±50.8] than the moderate intensity group (MD=40.3±27.5; t=-5.252, P<0.001). Change in lactate AUC and FDG-PET SUVR correlated significantly (R2=0.179, P<0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted. KEY POINTS: Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease. Blood lactate levels increase following acute exercise. Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel. Acute exercise stimulates changes in brain-derived neurotrophic factor and other blood biomarkers.

Brain health: Disease correlation and artificial intelligence

The brain is one of the most vital organs for us to perform through daily activity. But due to the lifestyle changes within modern society as the consequences of advancement of technology, more health issues have got into the public. Dementia and stroke are the two leading disability causes that are highly associated with the changes in modern society and the lack of brain health concepts for the general population. This article focuses on the two diseases, and how does it impact on brain health and correlate with daily lifestyle, moreover, the aim is to prevent the occurrence and promote healthier brain health to fulfill the performance. Artificial intelligence (AI) is a revolutionary technology that can help improve brain health from many perspectives. AI can not only help doctors diagnose neurological diseases, but also assess an individual's cognitive function. Advances in AI can deepen our understanding of neuroscience, making it possible for stroke and dementia patients to recover through devices implanted in the brain that coordinate all signals and function normally, just like a normal brain. Advances in AI bring hope to neuroscience research. Also, with the development of AI techniques, it can lead to changes in perspective of the ways to develop in the future neuroscience industry as well as assist in brain health.

Impact of yoga-based interventions on cognitive and autonomic functions in major depressive disorder population.

Cognitive and autonomic dysfunction is increasingly being recognized as an important clinical dimension in major depressive disorder. The aim of this study is to evaluate the effect of a combined approach of yoga and diet intervention on cognitive and autonomic functions in individuals with major depressive disorders. This experimental observational study was conducted at RUHS College of Medical Sciences and Associated Hospitals, Jaipur, on the major depressive disorder population of either sex cognitive function (mini-mental score, Montreal cognitive protocol A and B, P300 latency and amplitude) and autonomic function parameters (frequency and time domain) were recorded at baseline and after three months of a combined approach of yoga and diet intervention. This study compared cognitive and autonomic function parameters at baseline and after three months of yoga and diet intervention in a major depressive disorder population. Analysis revealed a significant decrease in body mass index (<0.05), systolic blood pressure (<0.001), Hamilton rating scale for depression (<0.001), P300 latency (<0.001), standard deviation of NN interval (SDNN) (<0.001), and mean heart rate (<0.001), whereas there was a significant increase in mini-mental score (<0.001), Montreal cognitive protocol A and B (<0.001), high frequency (HF) (<0.001), root mean square standard deviation (RMSSD) (<0.001), and PNN50 (<0.001) after a combined approach of yoga and diet in the study group as compared to control group participants. Yoga and diet combined may be an effective adjunct therapy for improving brain health and mental performance, lowering the risk of depression by affecting the neurotransmitter system and raising vagal tone which contributes to learning and memory.

Accumulation of damaged mitochondria in aging astrocytes due to mitophagy dysfunction: Implications for susceptibility to mitochondrial stress

Aging disrupts brain function, leading to cognitive decline and neurodegenerative diseases. Senescent astrocytes, a hallmark of aging, contribute to this process through unknown mechanisms. This study investigates how senescence impacts astrocytic mitochondrial dynamics, which are critical for brain health. Our research, conducted using aged mouse brains, represents the first evidence of morphologically damaged mitochondria in astrocytes, along with functional alterations in mitochondrial respiration. In vitro experiments revealed that senescent astrocytes exhibit an increase in mitochondrial fragmentation and impaired mitophagy. Concurrently, there was an upregulation of mitochondrial biogenesis, indicating a compensatory response to mitochondrial damage. Importantly, these senescent astrocytes were more susceptible to mitochondrial stress, a vulnerability reversed by rapamycin treatment. These findings suggest a potential link between senescence, impaired mitochondrial quality control, and increased susceptibility to mitochondrial stress in astrocytes. Overall, our study highlights the importance of addressing mitochondrial dysfunction and senescence-related changes in astrocytes as a promising approach for developing therapies to counter age-related neurodegeneration and improve brain health.

Peripheral, but not central, IGF-1 treatment attenuates stroke-induced cognitive impairment in middle-aged female Sprague Dawley rats: The gut as a therapeutic target

Stroke results in immediate sensory or motor disability and increases the risk for long term cognitive-affective impairments. Thus, therapies are urgently needed to improve quality of life for stroke survivors, especially women who are at a greater risk for severe stroke after menopause. Most current research on stroke therapies target the central nervous system; however, stroke also impacts peripheral organ systems. Our studies using acyclic (estrogen-deficient) middle aged female Sprague Dawley rats show that this group not only displays worse outcomes after stroke as compared to adult females, but also has lower levels of the neuroprotective peptide Insulin-like Growth Factor (IGF1) in circulation. Intracerebroventricular (ICV) administration of IGF1 to this group decreases infarct volume and improves sensory motor performance in the acute phase. In this study, we show that, despite this neuroprotection, ICV-IGF1 did not reduce peripheral inflammation or improve post stroke cognitive impairment in the chronic phase. In view of the evidence that stroke induces rapid gut dysfunction, we tested whether systemic delivery of IGF1 (intraperitoneal, IP) would promote gut health and consequently improve long-term behavioral outcomes. Surprisingly, while IP-IGF1, delivered 4 h and 24 h after ischemic stroke, did not reduce infarct volume or acute sensory motor impairment, it significantly attenuated circulating levels of pro-inflammatory cytokines, and attenuated stroke-induced cognitive impairment. In addition, IP-IGF1 treatment reduced gut dysmorphology and gut dysbiosis. Our data support the conclusion that therapeutics targeting peripheral targets are critical for long-term stroke recovery, and that gut repair is a novel therapeutic target to improve brain health in aging females.

Genetic evidence supports a causal relationship between air pollution and brain imaging-derived phenotypes

BackgroundObservational studies have reported associations between air pollutants and brain imaging-derived phenotypes (IDPs); however, whether this relationship is causal remains uncertain. MethodsWe conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the causal relationships between 5 types of air pollutants (N=423,796 to 456,380 individuals) and 587 reliable IDPs (N=33,224 individuals). Two-step MR was also conducted to assess whether the identified effects are mediated through the modulation of circulating cytokines (N=8293). ResultsWe found genetic evidence supporting the association of nitrogen oxides (NOx) with mean intra-cellular volume fraction (ICVF) in the left uncinate fasciculus (IVW β=-0.42, 95 % CI −0.62 to −0.23, P=1.51×10−5) and mean fractional anisotropy (FA) in the left uncinate fasciculus (IVW β=-0.42, 95 % CI −0.62 to −0.21, P=4.89×10−5). In further two-step MR analyses, we did not find evidence that genetic predictions of any circulating cytokines mediated the association between NOx and IDPs. ConclusionThis study provides evidence for the association between air pollutants and brain IDPs, emphasizing the importance of controlling air pollution to improve brain health.

Association of Metabolic Syndrome With Neuroimaging and Cognitive Outcomes in the UK Biobank.

Metabolic syndrome (MetS) has been linked to dementia. In this study, we examined the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the impact of MetS on brain health prior to dementia onset. We included 37,395 dementia-free adults from the UK Biobank database. MetS was defined as having at least three of the following components: larger waist circumference; elevated levels of triglycerides, blood pressure, HbA1c; or reduced HDL cholesterol levels. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. MetS was associated with lower total brain (standardized β: -0.06; 95% CI -0.08, -0.04), gray matter (β: -0.10; 95% CI -0.12, -0.08) and hippocampal (for left side, β: -0.03, 95% CI -0.05, -0.01; for right side, β: -0.04, 95% CI -0.07, -0.02) volumes, and greater white matter hyperintensity (WMH) volume (β: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (β: -0.10; 95% CI -0.13, -0.07), verbal declarative memory (β: -0.08; 95% CI -0.11, -0.05), processing speed (β: -0.06; 95% CI -0.09, -0.04), verbal and numerical reasoning (β: -0.07; 95% CI -0.09, -0.04), nonverbal reasoning (β: -0.03; 95% CI -0.05, -0.01), and on tests of executive function, where higher scores indicated poorer performance (β: 0.05; 95% CI 0.03, 0.08). More MetS components were also associated with less brain volume, greater WMH, and poorer cognition across all domains. MetS was associated poorer brain health in dementia-free adults, characterized by less brain volume, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health.

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents

IntroductionAmbient air pollution is a neurotoxicant with hypothesized immune-related mechanisms. Adolescent brain structural and functional connectivity may be especially vulnerable to ambient pollution due to the refinement of large-scale brain networks during this period, which vary by sex and have important implications for cognitive, behavioral, and emotional functioning. In the current study we explored associations between air pollutants, immune markers, and structural and functional connectivity in early adolescence by leveraging cross-sectional sex-stratified data from the Adolescent Brain Cognitive Development℠ Study®. MethodsPollutant concentrations of fine particulate matter, nitrogen dioxide, and ozone were assigned to each child's primary residential address during the prenatal period and childhood (9-10 years-old) using an ensemble-based modeling approach. Data collected at 11-13 years-old included resting-state functional connectivity of the default mode, frontoparietal, and salience networks and limbic regions of interest, intracellular directional and isotropic diffusion of available white matter tracts, and markers of cellular immune activation. Using partial least squares correlation, a multivariate data-driven method that identifies important variables within latent dimensions, we investigated associations between 1) pollutants and structural and functional connectivity, 2) pollutants and immune markers, and 3) immune markers and structural and functional connectivity, in each sex separately. ResultsAir pollution exposure was related to white matter intracellular directional and isotropic diffusion at ages 11–13 years, but the direction of associations varied by sex. There were no associations between pollutants and resting-state functional connectivity at ages 11–13 years. Childhood exposure to nitrogen dioxide was negatively correlated with white blood cell count in males. Immune biomarkers were positively correlated with white matter intracellular directional diffusion in females and both white matter intracellular directional and isotropic diffusion in males. Lastly, there was a reliable negative correlation between lymphocyte-to-monocyte ratio and default mode network resting-state functional connectivity in females, as well as a compromised immune marker profile associated with lower resting-state functional connectivity between the salience network and the left hippocampus in males. In post-hoc exploratory analyses, we found that the PLSC-identified white matter tracts and resting-state networks related to processing speed and cognitive control performance from the NIH Toolbox. ConclusionsWe identified novel links between childhood nitrogen dioxide and cellular immune activation in males, and brain network connectivity and immune markers in both sexes. Future research should explore the potentially mediating role of immune activity in how pollutants affect neurological outcomes as well as the potential consequences of immune-related patterns of brain connectivity in service of improved brain health for all.

SVHRSP Alleviates Age-Related Cognitive Deficiency by Reducing Oxidative Stress and Neuroinflammation.

Our previous studies have shown that scorpion venom heat-resistant synthesized peptide (SVHRSP) induces a significant extension in lifespan and improvements in age-related physiological functions in worms. However, the mechanism underlying the potential anti-aging effects of SVHRSP in mammals remains elusive. Following SVHRSP treatment in senescence-accelerated mouse resistant 1 (SAMR1) or senescence-accelerated mouse prone 8 (SAMP8) mice, behavioral tests were conducted and brain tissues were collected for morphological analysis, electrophysiology experiments, flow cytometry, and protein or gene expression. The human neuroblastoma cell line (SH-SY5Y) was subjected to H2O2 treatment in cell experiments, aiming to establish a cytotoxic model that mimics cellular senescence. This model was utilized to investigate the regulatory mechanisms underlying oxidative stress and neuroinflammation associated with age-related cognitive impairment mediated by SVHRSP. SVHRSP significantly ameliorated age-related cognitive decline, enhanced long-term potentiation, restored synaptic loss, and upregulated the expression of synaptic proteins, therefore indicating an improvement in synaptic plasticity. Moreover, SVHRSP demonstrated a decline in senescent markers, including SA-β-gal enzyme activity, P16, P21, SIRT1, and cell cycle arrest. The underlying mechanisms involve an upregulation of antioxidant enzyme activity and a reduction in oxidative stress-induced damage. Furthermore, SVHRSP regulated the nucleoplasmic distribution of NRF2 through the SIRT1-P53 pathway. Further investigation indicated a reduction in the expression of proinflammatory factors in the brain after SVHRSP treatment. SVHRSP attenuated neuroinflammation by regulating the NF-κB nucleoplasmic distribution and inhibiting microglial and astrocytic activation through the SIRT1-NF-κB pathway. Additionally, SVHRSP significantly augmented Nissl body count while suppressing neuronal loss. SVHRSP could remarkably improve cognitive deficiency by inhibiting oxidative stress and neuroinflammation, thus representing an effective strategy to improve brain health.

Augmented muscle mass blunts aging-induced cerebrovascular oxidant stress and inflammation

Cerebrovascular dysfunction is a key driver in the cognitive and sensorimotor decline that accompanies aging, contributing to the overall progression of vascular dementia. Exercise is an effective intervention to improve brain health and cognitive function, demonstrating positive effects on cerebral vasculature via a reduction in oxidant stress, thus delaying or partially reversing dementia symptoms. Age-related muscle loss (sarcopenia), however, is prevalent in adults over 50 and sarcopenic older individuals are frequently unable to take advantage of regular exercise, the most effective therapy to reduce risk of cognitive impairment, at a level that confers benefit. Interventions that can effectively replicate the effect of exercise are thus urgently needed to address the medical needs of a large population at exceedingly elevated risk for age-related cognitive impairment. The objective of the work is to determine if augmented muscle mass, a by-product of exercise, can ameliorate both skeletal and cerebrovascular dysfunction in an aging mouse model. Myokine myostatin is a potent negative regulator of skeletal muscle growth that contributes to reduced muscle mass in many muscle-wasting diseases, including aging. To date, research has focused on the protective effect of augmented muscle mass, using genetic or pharmaceutical inhibition of myostatin, in young and obese animals. Our hypothesis is that augmented muscle mass, via myostatin deletion, will improve muscle function and further, blunt the increase in oxidant stress and inflammation that drive cerebrovascular dysfunction in the aging brain. Young adult (3 mo.) and aged (24 mo.) male C57Bl/6J mice were used as controls, in combination with aged mice (24 mo.) with myostatin constitutively deleted. Augmented muscle mass and function were assessed using in vivo plantarflexion. Oxidant stress and inflammatory makers were assessed in micro vessels isolated from the whole brain, using commercially available ELISA’s and mRNA expression. Vascular function is being assessed using pressure myography and immunohistochemistry using the middle cerebral artery. Results show that augmented muscle mass, via myostatin deletion, was successful at increasing muscle mass in the aging mouse, blunting sarcopenia, and improving skeletal muscle function. Further, the aging cerebrovasculature had significantly increased expression of two of the NADPH oxidase isoforms (NOX1, NOX4), along with pivotal cytokines/chemokines associated with vascular inflammation, activation of microglia and astrocytes, and neuroinflammation (IL-1β and CCL5/RANTES). Biomarkers of oxidant stress (3-nitrotyrosine and 8-isoprostane) were also significantly elevated with aging. Taken together, augmented muscle mass may be an effective therapeutic target to prevent and rescue cerebrovascular function and inhibit cognitive decline in an aging population. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Food-derived Peptides as Promising Neuroprotective Agents: Mechanism and Therapeutic Potential.

Many food-derived peptides have the potential to improve brain health and slow down neurodegeneration. Peptides are produced by the enzymatic hydrolysis of proteins from different food sources. These peptides have been shown to be involved in antioxidant and anti-inflammatory activity, neuro-transmission modulation, and gene expression regulation. Although few peptides directly affect chromatin remodeling and histone alterations, others indirectly affect the neuroprotection process by interfering with epigenetic changes. Fish-derived peptides have shown neuroprotective properties that reduce oxidative stress and improve motor dysfunction in Parkinson's disease models. Peptides from milk and eggs have been found to have anti-inflammatory properties that reduce inflammation and improve cognitive function in Alzheimer's disease models. These peptides are potential therapeutics for neurodegenerative diseases, but more study is required to assess their efficacy and the underlying neuroprotective benefits. Consequently, this review concentrated on each mechanism of action used by food-derived peptides that have neuroprotective advantages and applications in treating neurodegenerative diseases. This article highlights various pathways, such as inflammatory pathways, major oxidant pathways, apoptotic pathways, neurotransmitter modulation, and gene regulation through which food-derived peptides interact at the cellular level.

Smartphone app for lifestyle improvement improves brain health and boosts the vitality and cognitive function of healthy middle-aged adults.

The number of smartphone apps for brain training is increasing, and the number of people who are working on brain training is also increasing. However, researchers disagree about the effectiveness of brain training. Therefore, in this study, we conducted an intervention test with the participation of 70 healthy middle-aged men and women and measured the effect of smartphone apps on lifestyle improvement using brain healthcare quotient calculated from brain imaging data. As a result, in the intervention group, significant improvements were seen in fractional anisotropy (FA) of the whole brain, corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, external capsule, and superior longitudinal fasciculus. Additionally, in the intervention group, these FA increments correlated with improvements in cognitive function as measured by the trail-making test and vigor as measured by the Profile of Mood States 2nd Edition. The results of this study suggest that improving lifestyle habits through smartphone apps can improve brain health and cognitive and emotional performance of healthy middle-aged adults. This is consistent with previous research that suggests that FA integrity in the limbic-thalamo-cortical pathway influences cognitive function and emotion regulation.

Lifestyle for brain health and cognitive functioning in midlife to early late-life New Zealanders: Utility of the LIBRA index.

There is enormous potential to improve brain health and reduce the risk of cognitive decline and dementia based on modifiable risk factors. The Lifestyle for Brain Health (LIBRA) index was developed to quantify modifiable dementia risk or room for brain health improvement. The objective of the study was to investigate the utility of the LIBRA index in relation to cognitive functioning in a midlife to early late-life sample of New Zealanders. A subsample (n=1001) of the longitudinal New Zealand Health, Work and Retirement (NZHWR) study completed face-to-face cognitive assessments using the 'Kiwi' Addenbrooke's Cognitive Examination-Revised (ACE-R)in 2010 and again in 2012, in addition to completing biennial NZHWR surveys on socioeconomic, health and wellbeing aspects. The LIBRA index was calculated incorporating information on 8 out of 12 modifiable health and lifestyle factors for dementia. Unadjusted and adjusted regression models and mixed effects models were used to inspect associations of LIBRA with cognitive functioning, cognitive impairment, and cognitive decline. The analytical sample (n=881 [88.0%], after considering exclusion criteria and missing data) had a mean age of 63.1 (SD=6.5) years, 53.3% were female, 26.2% were Māori, and 61.7% were highly educated. Higher LIBRA scores (indicating higher modifiable dementia risk) were associated with lower cognitive functioning (B=-0.33, 95% CI=-0.52;-0.15, p<0.001) and a higher likelihood of cognitive impairment (OR=1.22, 95% CI=1.04; 1.42, p=0.013), but did not predict cognitive decline over 2years (B=-0.03, 95% CI=-0.22; 0.16, p=0.766), adjusted for age, age2, gender, education, and ethnicity. The LIBRA index indicated promising utility for quantifying modifiable dementia risk in midlife and early late-life New Zealanders. For local use, refinement of the LIBRA index should consider cultural differences in health and lifestyle risk factors, and further investigate its utility with a wider range of modifiable factors over a longer observation period.

Health literacy in older adults: The newest vital sign and its relation to cognition and healthy lifestyle behaviors

Health literacy tends to decrease with age, and lower health literacy has been associated with lower levels of physical function, mental health, and medication adherence. The present study examined health literacy in relation to cognition in a sample of community-dwelling older adults. The study also examined the impact of health literacy on engagement in healthy aging lifestyle behaviors. Participants included 128 older adults (age: M = 72.07, SD = 6.71; education: M = 16.34, SD = 2.56; 74% female) who completed a health literacy measure (Newest Vital Sign; NVS), a lifestyle behavior questionnaire (Healthy Aging Activity Engagement scale; HAAE), and several neuropsychological tests. The cognitive domains assessed included memory, executive function, and attention/working memory. Two variables were computed from the NVS to represent the health literacy factors of document and numeracy literacy; these factors demonstrated a small correlation (r = .18). Results revealed that attention/working memory, executive function, and memory were all significantly related to numeracy literacy and overall health literacy. Only memory was significantly related to document literacy. After accounting for age, education, and cognition, a hierarchical regression revealed that health literacy significantly predicted engagement in healthy aging lifestyle behaviors. Multiple cognitive abilities are necessary for searching, finding, and processing information to make health-related decisions. Health literacy accounted for a significant amount of variance in older adults’ engagement in everyday lifestyle behaviors. Health literacy skills may be an area of focus for intervention efforts to improve brain health in older adults.

The effects of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents: a meta-analysis.

Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the PubMed, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using ReviewManager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference (MD; before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants (60 children and 471 adolescents, 10.9-16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I2 test provided by ReviewManager software. The meta-analysis showed that there was no heterogeneity among the studies (P = 0.67, I2 = 0.00%). The combined effect of the interventions was significant (MD = 2.88, 95% CI: 1.53-4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This meta-analysis was registered at PROSPERO (registration ID: CRD42023439408).

Connectedness, feeling At home, and joyful Play (CAP): A place-based wellness model for cognitive health promotion in the community by the community

ABSTRACT As populations age, leveraging community resources to reduce dementia risk is increasingly vital for brain health. Using community-based participatory research methods, we co-developed and tested a pilot program with older adults in Metro Vancouver, Canada, to better understand and address brain health needs in community settings. Over 12 focus groups, older adults provided input which led to a place-based wellness model ‘Connectedness, feeling At home, and joyful Play’ (CAP). The CAP model was incorporated into an 8-week feasibility study, testing various components of a multi-domain realist controlled trial (n = 78). Older adults were recommended various existing activities in the community based on their CAP profiles. A ‘Finding Meaning in Aging’ mindful discussion program was added in response to older adults’ feedback on current gaps. Path analysis of preliminary data suggests that total attendance (β = .196, p = .070) improved brain health at week 8 by increasing a sense of playfulness at week 4 (β = .284, p = .002). Mindfulness (β = .215, p = .046) improved brain health by increasing a sense of at-homeness (β = .227, p = .025). Both pre- and post-implementation feedback from older adults centred the importance of friendship in late life, specifically to address late-life losses. The community-generated CAP model shows promise for place-based cognitive health promotion.