Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults

Blueberries (BB) contain an array of bioactive phenolic compounds that may play a protective role against various age-related diseases. Here we explored the metabolic fate of BB phenolics and their relationship to cognitive function after chronic (90 days) supplementation of freeze-dried BB (24 g d^-1, equivalent to 1 cup of fresh BB) or control in a randomized, double-blind, parallel study with 38 healthy older adults (60-75 years). Blood samples were collected at fasting (t = 0 h) and 2 h after a breakfast meal on days 0 (no treatment), 45, and 90, and a battery of cognitive tests was also conducted on these days. Hippuric acid, phloroglucinaldehyde, syringic acid, ferulic acid-glucuronide, cyanidin-3-O-galactoside, cyanidin-3-O-glucoside, malvidin-3-O-galactoside, malvidin-3-O-glucoside, peonidin-3-O-xyloside, peonidin glucuronide, and petunidin-3-O-glucoside concentrations were significantly altered after 90 days of BB consumption compared to control. Stepwise regression was used to assess the relationship between significantly altered concentrations of plasma phenolics and observed improvements in cognition. Among participants in the BB group, changes in switch errors on the task-switching test (TST) from day 0 to 90 were associated with changes in postprandial levels of plasma ferulic acid-glucuronide, syringic acid, and malvidin-3-galactoside (R² = 0.521, p < 0.05). Changes in repetition errors on the California Verbal Learning Test (CVLT-II) from day 0 to 90 were associated with changes in postprandial levels of ferulic acid-glucuronide, syringic acid, and hippuric acid (R² = 0.807, p < 0.001). These findings demonstrate that the addition of easily achievable quantities of BB to the diets of older adults significantly alters levels of circulating phenolic compounds which are related to improvements in cognition.