© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 996 Journals of Gerontology: Biological Sciences cite as: J Gerontol A Biol Sci Med Sci, 2019, Vol. 74, No. 7, 996–1007 doi:10.1093/gerona/gly166 Advance Access publication July 19, 2018 Special Section: Blueberries and Aging Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study Julien Bensalem, PhD, 1,2,3 Stéphanie Dudonné, PhD, 4,5 Nicole Etchamendy, PhD, 1,2 Hermine Pellay, MSc, 1,2,3 Camille Amadieu, MSc, 1,2 David Gaudout, MSc, 3 Séverine Dubreuil, MSc, 3 Marie-Eve Paradis, PhD, 4,5 Sonia Pomerleau, MSc, 4 Lucile Capuron, PhD, 1,2,5 Carol Hudon, PhD, 4,6 Sophie Layé, PhD, 1,2,5 , Yves Desjardins, PhD, 4,5 and Véronique Pallet, PhD, 1,2,5,7, * 1 Univ. de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France. 2 INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France. 3 Activ’Inside, Beychac et Caillau, France. 4 Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, Québec Canada. 5 OptiNutriBrain International Associated Laboratory (NutriNeuro France-INAF Canada), Bordeaux, France. 6 Centre de recherche de l’Institut universitaire en santé mentale de Québec, Québec, Canada. 7 Bordeaux INP, Nutrition et neurobiologie intégrée, UMR1286, Bordeaux, France. *Address correspondence to: Véronique Pallet, PhD, Laboratoire NutriNeurO, UMR INRA 1286, Université de Bordeaux, 146 rue Léo Saignat, 33046 Bordeaux, France. E-mail: veronique.pallet@enscbp.fr Received: November 19, 2017; Editorial Decision Date: June 28, 2018 Decision Editor: Rafael de Cabo, PhD Abstract Polyphenols are promising nutritional bioactives exhibiting benefcial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60–70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg favonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no signifcant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profle of decliners revealed that they excreted more metabolites. Urinary concentrations of specifc favan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments. Keywords: Cognition, Aging, Flavan-3-ols, CANTAB, PAL. In recent years, the demographic weight of elderly has increased signifcantly in most industrialized countries. This segment of the population is estimated to reach up to 2 billion in 2050 (1). Ageing is inexorably accompanied by a more or less severe age-related cog- nitive decline (ARCD), defned as a non-pathological, yet signifcant decrease in elementary and advanced mental abilities (2,3). It usu- ally develops progressively from midlife onward (between 35 and 65 years) (4). Among cognitive impairments, memory loss is one of the most serious health concerns for elderly (2,3). Accordingly, strat- egies to prevent, delay, or slow-down ARCD is becoming a critical Downloaded from https://academic.oup.com/biomedgerontology/article/74/7/996/5056005 by guest on 03 December 2022