The primary objective of the SmartAge trial is to provide evidence of a beneficial impact of nutritional spermidine on memory performance (primary outcome) at the end of the intervention, as compared with placebo. In case the answer to question 2 is at least 6months, question 3 will be asked: Are you concerned about this cognitive worsening? (German: Bereitet Ihnen diese Verschlechterung Sorgen?, possible answers: yes/no). What is Spermidine? Moreover, this behavioral marker is closely tied to neural dysfunction in the hippocampal memory network [48, 49] and has been identified as a sensitive outcome measure in olderindividuals at higherrisk of AD [39]. Statistical analyses of the primary outcome will be conducted by a designated statistician. The follow-up visit will take place 18months after baseline visit. 2011;68:6449. PubMedGoogle Scholar. 2006;27:17516. We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Musa M, Zeppieri M, Atuanya GN, Enaholo ES, Topah EK, Ojo OM, Salati C. Life (Basel). Participants will be instructed to immediately contact the research team in case of any self-noticed health changes or unexpected medical care visits. This amount of daily polyamine intake accounts for an increase of approximately 1020% of the average spermidine intake in industrial countries [46]. Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats. All SAEs (whether or not related to the intervention) and all relevant pseudonymized documentation related to the SAE will be documented in the SAE report form, dated and signed by the principal investigator and included in the CRF documentation. india news podcast. Schwarz C, Wirth M, Gerischer L, Grittner U, Witte AV, Kobe T, Floel A. However, some research suggests that a daily dosage of around 6mg of spermidine could be effective in providing health benefits ( source ). Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. 2023 May 2;45(5):3911-3932. doi: 10.3390/cimb45050250. The Age-Well randomized controlled trial of the Medit-Ageing European project: Effect of meditation or foreign language training on brain and mental health in older adults. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. Google Scholar. Higher spermidine intake is linked to lower mortality: a prospective Back to top Can spermidineLIFE Trigger Food Allergies? MW established the design of the trial and led the drafting of the study protocol. It is naturally occurring and is widely encountered in ribosomes and living tissues. Effects of spermidine supplementation on cognition and biomarkers in CAS Hogrefe, Verlag fr Psychologie; 1998. Neurology. To ensure the standardization of data collection, all study assessors will undergo systematic training. The visit will include following assessments: standardized screening assessment, standardized medical examination without blood draw, and adapted versions of the standardized neuropsychological test battery and questionnaire battery (see Table1). Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chetelat G, Dubois B, Dufouil C, Ellis KA, van der Flier WM, et al: A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Polyamine levels (spermidine, spermine, and putrescine), metabolomics, proinflammatory biomarkers, and neurotrophin levels in whole blood, serum and plasma samples will be analyzed by the Institute of Molecular Biosciences, University of Graz, Austria. Springer Nature. J Alzheimers Dis. FDA Approves New Buprenorphine Treatment Option for Opioid Use Disorder Champely S, Ekstrom C, Dalgaard P, Gill J, Wunder, J., De Rosario H: pwr: basic functions for power analysis. Charit Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz fr Neurologie, Berlin, Germany, Miranka Wirth,Claudia Schwarz,Gloria Benson,Nora Horn,Theresa Kbe&Ute Kopp, Charit Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, Berlin, Germany, Miranka Wirth,Claudia Schwarz,Gloria Benson,Nora Horn,Theresa Kbe,Marta Maglione,Eva Michael,Stefanie Mrschenz,Dietmar Schmitz&Stephan J. Sigrist, Charit Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany, German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany, Charit - Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Berlin, Germany, University Hospital Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Hamburg, Germany, Douglas Mental Health University Institute, Studies on Prevention of Alzheimers Disease (StOP-AD) Centre, Montreal, Quebec, Canada, Department of Psychiatry, McGill University, Montreal, Quebec, Canada, Charit Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Berlin Center for Advanced Neuroimaging, Berlin, Germany, Bernstein Center for Computational Neuroscience, Berlin, Germany, Institute for Biology/Genetics, Freie Universitt Berlin, Berlin, Germany, Marta Maglione,Eva Michael&Stephan J. Sigrist, Charit - Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Department of Endocrinology & Metabolism, Berlin, Germany, Charit-Center for Cardiovascular Research (CCR), Berlin, Germany, German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany, Charit Universittsmedizin Berlin, Corporate Member of Freie Universitt Berlin, Humboldt-Universitt zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany, Berlin Institute of Health (BIH), Berlin, Germany, Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria, Department of Neurology, University Medicine Greifswald, Greifswald, Germany, German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany, You can also search for this author in A positive outcome with regard to memory performance in the spermidine-treated group may initiate a large multi-center phase III trial with a profound impact on public health, patients with SCD, and their families. Wrselen: Psytest; 2012. Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. In addition, we will assess memory performance at 18months and outcome measures of other neurocognitive domains as well as behavioral and physiological parameters to evaluate further benefitsof the intervention. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. 2013;16:145360. Psychiatry Res. Manual for the state-trait anxiety inventory; 1970. RB and CL were responsible for the approval and implementation of the PET protocol. In rodent models, polyamine levels in the hippocampus are shown to be associated with memory retrieval and formation [28] and change with age in certain brain areas, including medial-temporal memory structures [29]. 2018;4:73745. The .gov means its official. 1998;37:23441. Federal government websites often end in .gov or .mil. Samples will be stored at 80C until analysis. All AEs and SAEs will be reported to and documented by the responsible study physician (SAEs within 24h). HHS Vulnerability Disclosure, Help CAS Spermidine has been tested and discovered to encourage hair shaft elongation and lengthen hair growth. Front Aging Neurosci. 2015;7:134. 2023 BioMed Central Ltd unless otherwise stated. 2017;27:176578. One early sign of pathological brain aging is the manifestation of subjective cognitive decline (SCD). . Biopsy tissue processing will include snap freezing in liquid nitrogen and paraffin embedding. If you are allergic to wheat or gluten, or you have a gluten sensitivity, we do not recommend taking spermidineLIFE. MW, GB, and UK designed the neuropsychological test battery and questionnaire battery. In this pre-study on 30 SCD participants (dropout: n=2) and a 3-month intervention period, we determined an effect size of Cohens d=0.65 on the group difference in change of mnemonic discrimination performance between baseline (V1) and the end of intervention (V2). Neuropsychol Rev. Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. Spermidine is a polyamine, meaning it has two or more primary amino groups. Nat Neurosci. Ann N Y Acad Sci. The occurrence of AEs and SAEs will be constantly monitored throughout the SmartAge trial. Larger multi-center phase III trials with 10002000 participants and trial durations of 1.52years commonly select clinical outcome measures, which are however less sensitive [84]. May 23, 2023. Our initial short-term (3months) phase IIa trial demonstrated that spermidine supplementation is an easy-to-use, safe, and well-tolerated intervention [36]. 2010;75:299301. An official website of the United States government. First off it is a whole grain which means each kernel includes bran, germ and endosperms. Polcher A, Frommann I, Koppara A, Wolfsgruber S, Jessen F, Wagner M. Face-name associative recognition deficits in subjective cognitive decline and mild cognitive impairment. Manual: Hogrefe; 2007. CAS Spermidine FAQ What is Spermidine? No claim to original U.S. Government Works. Floel A, Witte AV, Lohmann H, Wersching H, Ringelstein EB, Berger K, Knecht S. Lifestyle and memory in the elderly. Psychol Med. Z Ernahrungswiss. 2017;14:229. 2002;57:P1927. Nuklearmedizin. Oldfield RC. It contains 50 mg of spermidine, relatively it is less than others however still according to the food type this amount can be considered as descent. . The effect of spermidine on memory performance in older adults at risk for dementia: a randomized controlled trial. The https:// ensures that you are connecting to the 2014;13:198794. Blood samples for Labor Berlin Charit Vivantes GmbH will be shipped immediately. Your US state privacy rights, Google Scholar. Thus, SCD has been conceptualized to occur at a late preclinical stage of AD [15], where aberrant brain changes are present [16] in the absence of objective cognitive impairment. dosage, sources and risk. This data will help to estimate potential benefits of nutrition intervention on well-being andeveryday life. In this model, change in memory performance (V3V1) will represent the dependent variable, with intervention group as the independent variable and baseline scores and age inserted as covariate. This site needs JavaScript to work properly. SM, MM, and EM participated in the implementation and/or conductance of the laboratory analyses. Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)study protocol for a randomized controlled trial. Hum Brain Mapp. haben Sie dies bereits getan?, possible answers: yes/no). Wirth, M., Schwarz, C., Benson, G. et al. Neocortical A-plaques burden will be evaluated as the average FBB SUVr within a predefined composite of cortical regions-of-interest [76]. Alzheimers Dement (N Y). Functional MRI will include an associative face-name memory task, adapted and modified from a previous publication [68]. Biogerontology. Privacy Today, the U.S. Food and Drug Administration approved Brixadi (buprenorphine) extended-release injection for subcutaneous use (under the skin) to treat moderate to severe opioid use . 2017;76:20312. Dosage of Spermidine and Its Effect for Maximum Health Benefits. Beyond these microscopic actions, there is an indication that polyamines influence macroscopic systems underlying learning and memory as well as age-related changes of this cognitive function. https://doi.org/10.1186/s13195-019-0484-1, DOI: https://doi.org/10.1186/s13195-019-0484-1. PubMed We will conduct a randomized controlled trial with a 12-month spermidine supplementation in cognitively unimpaired older individuals with SCD (n=100). Epub 2020 Sep 26. Effects of Spermidine Supplementation on Cognition and Biomarkers in What is SPERMIDINE?! Meet the Latest Longevity Ingredient - PricePlow CAS Prehn K, Jumpertz von Schwartzenberg R, Mai K, Zeitz U, Witte AV, Hampel D, Szela AM, Fabian S, Grittner U, Spranger J, Floel A. Caloric restriction in older adults-differential effects of weight loss and reduced weight on brain structure and function. In addition, non-invasive measurements of muscle function and muscle strength will be assessed during medical examination from all participants who consented to muscle biopsy, to determine age-related sarcopenia. Gerontologist. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity. The expected dropout rate will be balanced in advance by the number of participants. Advice on how to hold back the ageing process PubMed Wilson R, Barnes L, Bennett D. Assessment of lifetime participation in cognitively stimulating activities. 1992;12:57183. 2017;147:66977. Research question and aim. 7 daily habits to shed weight quickly. Validation of the German version of the Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Aging (Albany NY). ClinicalTrials.gov, NCT03094546. Without a doubt, spermidine is an extraordinary molecule. The post-invention visit will take place at the end of the 12-month intervention period. 2012;22:106874. Buyukuslu N, Hizli H, Esin K, Garipagaoglu M. A cross-sectional study: nutritional polyamines in frequently consumed foods of the Turkish population. It will further be investigated whether demographic or biological factors are associated with primary and secondary endpoints and / or modulate the response to the intervention, by integrating these variables into statistical models as covariates (or as interactive term with the intervention group).