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

Abstract

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. The present 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 flavonoids) 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 significant 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 profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-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.

The Effect of (Poly)phenol-Rich Interventions on Cognitive Functions and Neuroprotective Measures in Healthy Aging Adults: A Systematic Review and Meta-Analysis

“…Fifteen studies [26][27][28][29][30][31][35][36][37][40][41][42][43][44][45] met the inclusion criteria and were included in the current systematic review. The studies examined the effects of (poly)phenol-rich supplementation intake on cognitive functions and/or brain-related parameters (e.g., neuroimaging, neuroplasticity, CBF, etc).…”

“…The characteristics of each study as well as the cognitive and the neurological changes following rich-(poly)phenol supplementation compared to placebo supplementation are summarized in Tables 2 and 3, respectively. Eight papers [26,27,35,36,40,41,43,44] examined only the effect of rich-(poly)phenol supplementation on different cognitive functions such as visual attention, working memory, reaction time, executive functioning, and learning abilities. Five studies [28,29,31,37,42] examined the effect of rich-(poly)phenol supplementation on cognitive function as well as a variety of brain-related parameters such as brain perfusion, cerebral blood flow, cerebral hemodynamics, hippocampal functional connectivity, neuroplasticity, neuroinflammation, and other brain-related parameters.…”

“…Two studies [30,45] only examined the change in cerebral blood flow parameters following rich-(poly)phenol supplementation without cognitive function measurements. Concerning the acute (up to 2 h) and chronic effects of (poly)phenol-rich supplementation on the abovementioned functions, twelve studies investigated the chronic effect [26,27,29,31,35,36,[40][41][42][43][44][45], two studies investigated only the acute effect [30,37], and only one study [28] investigated both acute and chronic effect of (poly)phenol-rich supplementation on cognitive and brain functions.…”

“…As presented in Tables 2 and 3, all reviewed studies employed a randomized design. Eight studies employed two parallel experimental arms, with seven of them using placebo and rich-(poly)phenol supplementation as treatment arms [29,31,35,[41][42][43][44], while the remaining study [45] used poorand rich-(poly)phenol supplementation as treatment arms. Two studies employed three parallel experimental arms with one study using placebo as the control arm and low and high (poly)phenol doses as treatment arms [40] and the second using only (poly)phenol supplementation at different doses (i.e., low, moderate, and high) [26].…”

“…Three studies [35,36,43] opted for isoflavones extract treatment with a dose ranging from 55 mg/day to 110 mg/day (high dose). Three studies opted for blueberry-based extract treatment that allowed for a total daily (poly)phenol dose ranging from 35 mg to 70 mg in the study of Whyte et al [27], a daily flavonoids dose of 258 mg in the study of Bensalem et al [41], or a daily anthocyanidins dose of 387 as reported in the study of Bowtell et al [31]. Four studies opted for rich-flavanol cocoa treatment that allowed for a total daily (poly)phenol dose ranging from 85 mg to 395 mg in the study of Marsh et al [37] or a daily flavanol dose ranging from 29 mg (low dose) to 993 mg (high dose) as reported in the studies of Lamport et al [30] and Sorond et al [45].…”