Sebastian Huhn1, Frauke Beyer2, Rui Zhang3, Leonie Lampe4, Jana Grothe5, Jürgen Kratzsch6, Anja Willenberg7, Jana Breitfeld8, Peter Kovacs9, Michael Stumvoll10, Robert Trampel11, Pierre-Louis Bazin12, Arno Villringer13, A Veronica Witte14. 1. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Electronic address: huhn@cbs.mpg.de. 2. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Electronic address: fbeyer@cbs.mpg.de. 3. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Electronic address: zhang@cbs.mpg.de. 4. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany. Electronic address: lampe@cbs.mpg.de. 5. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany. Electronic address: grothe@cbs.mpg.de. 6. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany. Electronic address: juergen.kratzsch@medizin.uni-leipzig.de. 7. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany. Electronic address: anja.willenberg@medizin.uni-leipzig.de. 8. Leipzig University Medical Center, IFB AdiposityDiseases, Leipzig, Germany. Electronic address: jana.breitfeld@medizin.uni-leipzig.de. 9. Leipzig University Medical Center, IFB AdiposityDiseases, Leipzig, Germany. Electronic address: peter.kovacs@medizin.uni-leipzig.de. 10. Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany; IFB Adiposity Diseases, Medical Research Centre, University of Leipzig, Leipzig, Germany. Electronic address: michael.stumvoll@uniklinik-leipzig.de. 11. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany. Electronic address: trampel@cbs.mpg.de. 12. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Spinoza Centre for Neuroimaging, Amsterdam, Netherlands; Netherlands Institute for Neuroscience, Amsterdam, Netherlands. Electronic address: bazin@cbs.mpg.de. 13. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Electronic address: villringer@cbs.mpg.de. 14. Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Stephanstr. 1A, 04103 Leipzig, Germany; Collaborative Research Centre 1052 'Obesity Mechanisms', Subproject A1, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Electronic address: witte@cbs.mpg.de.
Abstract
INTRODUCTION: The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie-restriction mimicking effects. However, the evidence based on human interventional studies is scarce. We therefore aimed to determine the effects of resveratrol on memory performance, and to identify potential underlying mechanisms using a broad array of blood-based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra-high field magnetic resonance imaging (UHF-MRI). METHODS: In this double-blind, randomized controlled trial, 60 elderly participants (60-79 years) with a wide body-mass index (BMI) range of 21-37 kg/m2 were randomized to receive either resveratrol (200 mg/day) or placebo for 26 weeks (registered at ClinicalTrials.gov: NCT02621554). Baseline and follow-up assessments included the California Verbal Learning Task (CVLT, main outcome), the ModBent task, anthropometry, markers of glucose and lipid metabolism, inflammation and neurotrophins derived from fasting blood, multimodal neuroimaging at 3 and 7 T, and questionnaires to assess confounding factors. RESULTS: Multivariate repeated-measures ANOVA did not detect significant time by group effects for CVLT performance. There was a trend for preserved pattern recognition memory after resveratrol, while performance decreased in the placebo group (n.s., p = 0.07). Further exploratory analyses showed increases in both groups over time in body fat, cholesterol, fasting glucose, interleukin 6, high sensitive C-reactive protein, tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum, as well as decreases in physical activity, brain-derived neurotrophic factor and insulin-like growth factor 1 at follow-up, which were partly more pronounced after resveratrol. DISCUSSION: This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range. A non-significant trend emerged for positive effects on pattern recognition memory, while possible confounding effects of unfavorable changes in lifestyle behavior, neurotrophins and inflammatory markers occurred. Our findings also indicate the feasibility to detect (un)healthy aging-related changes in measures of hippocampus microstructure after 6 months using 7T diffusion MRI. More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults.
RCT Entities:
INTRODUCTION: The polyphenolresveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie-restriction mimicking effects. However, the evidence based on human interventional studies is scarce. We therefore aimed to determine the effects of resveratrol on memory performance, and to identify potential underlying mechanisms using a broad array of blood-based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra-high field magnetic resonance imaging (UHF-MRI). METHODS: In this double-blind, randomized controlled trial, 60 elderly participants (60-79 years) with a wide body-mass index (BMI) range of 21-37 kg/m2 were randomized to receive either resveratrol (200 mg/day) or placebo for 26 weeks (registered at ClinicalTrials.gov: NCT02621554). Baseline and follow-up assessments included the California Verbal Learning Task (CVLT, main outcome), the ModBent task, anthropometry, markers of glucose and lipid metabolism, inflammation and neurotrophins derived from fasting blood, multimodal neuroimaging at 3 and 7 T, and questionnaires to assess confounding factors. RESULTS: Multivariate repeated-measures ANOVA did not detect significant time by group effects for CVLT performance. There was a trend for preserved pattern recognition memory after resveratrol, while performance decreased in the placebo group (n.s., p = 0.07). Further exploratory analyses showed increases in both groups over time in body fat, cholesterol, fasting glucose, interleukin 6, high sensitive C-reactive protein, tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum, as well as decreases in physical activity, brain-derived neurotrophic factor and insulin-like growth factor 1 at follow-up, which were partly more pronounced after resveratrol. DISCUSSION: This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range. A non-significant trend emerged for positive effects on pattern recognition memory, while possible confounding effects of unfavorable changes in lifestyle behavior, neurotrophins and inflammatory markers occurred. Our findings also indicate the feasibility to detect (un)healthy aging-related changes in measures of hippocampus microstructure after 6 months using 7T diffusion MRI. More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults.
Authors: Pedro A Luque Laguna; Anna J E Combes; Johannes Streffer; Steven Einstein; Maarten Timmers; Steve C R Williams; Flavio Dell'Acqua Journal: Neuroimage Clin Date: 2020-01-25 Impact factor: 4.881