A Metabolic Intervention for Improving Human Cognitive Performance During Hypoxia

2021 ◽  
Vol 92 (7) ◽  
pp. 556-562
Author(s):  
Kody Coleman ◽  
Jeff Phillips ◽  
Michelle Sciarini ◽  
Brianna Stubbs ◽  
Olivia Jackson ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Brain Metabolism ◽  
Performance Test ◽  
Ketone Bodies ◽  
Acute Hypoxia ◽  
Placebo Control ◽  
Blink Rate ◽  
Alternative Substrate ◽  
Atp Production ◽  
Ketone Ester

BACKGROUND: During hypoxia an operators cognitive performance may decline. This decline is linked to altered brain metabolism, resulting in decreased adenosine triphosphate (ATP) production. Ketone bodies are an alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies in the blood maintains brain ATP levels and reduces cerebral glycolysis during hypoxia. Thus, ketones may be a strategy to mitigate cognitive decline in hypoxia. Ketone ester (KE) consumption allows rapid elevation of blood ketone levels; therefore, we investigated the effects of consuming a KE drink on cognitive performance during hypoxia. Here, we report results of a pilot study.METHODS: There were 11 subjects who completed a cognitive performance test battery under conditions of normoxia and hypoxia following consumption of a KE drink and a placebo control drink.RESULTS: Significant hypoxia effects (O2 saturation minimum was found to range between 63 and 88 in subjects) were found for blink duration (Ph2 0.665) and blink rate (Ph2 0.626), indicating that the hypoxia condition was associated with longer blink durations and lower blink rates. Significant hypoxia effects were likewise observed for a code substitution task (Ph2 0.487), indicating that performance on the task was significantly disrupted by the hypoxia stressor. KE consumption had a significant effect on blink duration (Ph2 0.270) and the code substitution task (Ph2 0.309).DISCUSSION: These finding suggest that some effects of acute hypoxia can be mitigated by nutritional ketosis.Coleman K, Phillips J, Sciarini M, Stubbs B, Jackson O, Kernagis D. A metabolic intervention for improving human cognitive performance during hypoxia. Aerosp Med Hum Perform. 2021; 92(7):556562.

Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults ≥ 55 Years Old. A Study Protocol for a Double-Blinded Randomized Controlled Clinical Trial

2022 ◽  
pp. 1-12
Author(s):  
K.I. Avgerinos ◽  
R.J. Mullins ◽  
J.M. Egan ◽  
D. Kapogiannis
Keyword(s):  
Metabolic Syndrome ◽  
Clinical Trial ◽  
Cognitive Performance ◽  
Animal Studies ◽  
Brain Metabolism ◽  
Ketone Bodies ◽  
Controlled Clinical Trial ◽  
Resonance Spectroscopy ◽  
Double Blinded ◽  
Cognitively Intact

BACKGROUND: Ketone bodies have been proposed as an “energy rescue” for the Alzheimer’s disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce. Objectives: To investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD. Design: Double-blinded randomized placebo-controlled clinical trial. Setting: Clinical Unit of the National Institute on Aging, Baltimore, US. Participants: Fifty cognitively intact adults ≥ 55 years old, with metabolic syndrome. Intervention: Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Outcomes: Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. Discussion: This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer’s effects in humans.

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

scholarly journals Cognition and renal function: findings from a Brazilian population

2019 ◽  
Vol 41 (2) ◽  
pp. 200-207 ◽  
Author(s):  
Viviane Bernardes de Oliveira Chaiben ◽  
Thabata Baechtold da Silveira ◽  
Murilo Henrique Guedes ◽  
João Pedro de Almeida Fernandes ◽  
João Henrique Fregadolli Ferreira ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Performance Test ◽  
Word List ◽  
Semantic Fluency ◽  
Explanatory Variables ◽  
Executive Performance ◽  
Potential Association ◽  
Trail Making ◽  
Potential Impact ◽  
List Memory

ABSTRACT Introduction: The prevalence of chronic kidney disease (CKD) is increasing, with a potential impact in the risk of acceleration of dementia. The potential association between glomerular filtration rate (eGFR) and cognitive performance was scarcely studied. The aim of this study was to evaluate cognitive performance levels across different degrees of kidney function. Methods: We analyzed 240 outpatients in a nephrology service, classified according to eGFR: Advanced (≤ 30ml/min/1.73m2), Moderate (30,1ml/min/1.73m2 to ≤ 60ml/min/1.73m2), and Mild CKD (> 60ml/min/1.73m2). Word list memory, Semantic fluency, Mental State Mini Exam and Trail Making Test (TMT) were applied to evaluate cognitive performance. In the TMT, lower scores are associated with better cognition. In linear regression, cognitive function was considered as dependent variables while groups based on eGFR were considered explanatory variables. The group with eGFR > 60ml/min was the reference and models were adjusted for confounding factors. Results: In our population (n = 240) 64 patients (26.7%) were classified as having advanced, 98(40,8%) moderate, and 78(32,5%) mild. There was no statistical difference among them in MMSE or in the verbal fluency test. However, comparing to mild, patients with advanced CKD presented significantly worse cognitive performance measured by TMTA [50,8s ± 31.1s versus 66,6s ± 35,7s (p = 0.016)] and TMTB [92,7s ± 46,2s versus 162,4s ± 35,7s (p < 0.001)]. Significantly lower TMTB scores (CI95%) 33,0s (4,5-61,6s) were observed in patients with mild compared to advanced CKD in the multivariate analysis adjusting for age, education, sex, diabetes, and alcohol use. Conclusion: Advanced CKD is independently associated with poorer cognitive performance measured by an executive performance test compared to mild CKD.

scholarly journals Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruzhou Zhao ◽  
Xingcheng Zhao ◽  
Xiaobo Wang ◽  
Yanqi Liu ◽  
Jie Yang ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Survival Rates ◽  
The Body ◽  
Utilization Efficiency ◽  
Ros Generation ◽  
Oxygen Utilization ◽  
Mtor Inhibition ◽  
Atp Production ◽  
Hypoxic Adaptation ◽  
Hypoxic Tolerance

AbstractRapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.

Methylphenidate Reduces State Anxiety During a Continuous Performance Test That Distinguishes Adult ADHD Patients From Controls

2016 ◽  
Vol 21 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Yuval Bloch ◽  
Shai Aviram ◽  
Aviv Segev ◽  
Uri Nitzan ◽  
Yechiel Levkovitz ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
State Anxiety ◽  
Cognitive Assessment ◽  
Adult Adhd ◽  
Performance Test ◽  
Cognitive Task ◽  
Continuous Performance Test ◽  
Effective Therapy ◽  
Continuous Performance ◽  
Functional Difficulties

Objective: We hypothesized that patients with ADHD were typified by distress more than by functional difficulties. Thus, a decline in state anxiety while performing a cognitive task when taking methylphenidate would discriminate between ADHD patients and controls. Method: State anxiety and cognitive performance on a continuous performance test were assessed in ADHD patients and controls with and without taking methylphenidate. Results: State anxiety and cognitive performance improved from baseline in 36 ADHD adults after taking methylphenidate. In 25 controls, cognitive performance improved, but state anxiety did not abate after a recess. In two additional studies, 5 controls were evaluated at baseline and after receiving methylphenidate, and showed improvement in cognitive assessment but not in state anxiety. Five ADHD adults were assessed at baseline and after a recess, and showed no improvement. Conclusion: Our results support the hypothesis that adult ADHD patients are characterized by distress and the relief of this distress under effective therapy as expressed by a decline in state anxiety while they perform a cognitive task.

scholarly journals Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8767
Author(s):  
Nicole Jacqueline Jensen ◽  
Helena Zander Wodschow ◽  
Malin Nilsson ◽  
Jørgen Rungby
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Metabolism ◽  
Ketone Bodies ◽  
Current Knowledge ◽  
Ketogenic Diets ◽  
Cognitive Benefits ◽  
The Brain

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

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