The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Miranka Wirth; Gloria Benson; Claudia Schwarz; Theresa Köbe; Ulrike Grittner; Dietmar Schmitz; Stephan J Sigrist; Jens Bohlken; Slaven Stekovic; Frank Madeo; Agnes Flöel

doi:10.1016/j.cortex.2018.09.014

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Cortex. 2018 Dec:109:181-188. doi: 10.1016/j.cortex.2018.09.014. Epub 2018 Oct 4.

Authors

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Center for Stroke Research, Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany. Electronic address: gloria.benson@charite.de.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany. Electronic address: claudia.schwarz@charite.de.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease Centre, Montreal, Quebec, Canada. Electronic address: theresa.koebe@charite.de.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. Electronic address: ulrike.grittner@charite.de.
⁶ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany. Electronic address: dietmar.schmitz@charite.de.
⁷ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany; Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany. Electronic address: stephan.sigrist@fu-berlin.de.
⁸ Medical Practice Bohlken for Neurology and Psychiatry, Berlin, Germany. Electronic address: dr.j.bohlken@gmx.net.
⁹ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria; BioTechMed Graz, Graz, Austria. Electronic address: slaven.stekovic@uni-graz.at.
¹⁰ Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria; BioTechMed Graz, Graz, Austria. Electronic address: frank.madeo@uni-graz.at.
¹¹ Department of Neurology, University Medicine Greifswald, Greifswald, Germany. Electronic address: agnes.floeel@uni-greifswald.de.

PMID: 30388439
DOI: 10.1016/j.cortex.2018.09.014

Abstract

Introduction: Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer's disease.

Methods: Cognitively intact participants with subjective cognitive decline (n = 30, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.

Results: Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): -.01, .35, Cohen's d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -.11, 95% CI: -.19, -.03, Cohen's d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: -.13, .27, Cohen's d = -.20, 95% CI: -.94, .54).

Discussion: In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action.

Trial registration: Registered in ClinicalTrials.gov with the Identifier NCT02755246.

Keywords: Cognition; Diet supplementation; Polyamine; Prevention; SmartAge; Subjective cognitive decline.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Cognitive Dysfunction / psychology*
Dementia / psychology*
Dietary Supplements*
Double-Blind Method
Female
Humans
Male
Memory / drug effects*
Middle Aged
Neuropsychological Tests
Risk Factors
Spermidine / pharmacology*

Substances

Spermidine

Associated data

ClinicalTrials.gov/NCT02755246