Blueberry Supplementation in Midlife for Dementia Risk Reduction

Abstract

Late-life dementia typically develops over a period of many years beginning in midlife. Prevalence of metabolic disturbance also accelerates in middle age and is a prominent risk factor for dementia. Preliminary studies indicate that blueberry supplementation can improve cognitive performance and influence metabolism and brain function and therefore may have a role in early intervention to prevent neurodegeneration. In a randomized controlled trial, we investigated the effects of daily blueberry supplementation in a middle-aged sample of insulin-resistant participants with elevated risk for future dementia. We enrolled overweight men and women, aged 50 to 65 years, with subjective cognitive decline (SCD) and performed pre- and post-intervention assessments of cognition and metabolism and exploratory measures of peripheral mitochondrial function. We observed improved performances for the blueberry group on measures of lexical access, p = 0.003, and memory interference, p = 0.04, and blueberry-treated participants reported reduced memory encoding difficulty in daily life activities, p = 0.03. The blueberry-treated group also exhibited correction of peripheral hyperinsulinemia, p = 0.04, and a modest trend for increased mitochondrial uncoupling, p = 0.11. The cognitive findings indicated improved executive ability in this middle-aged sample. In addition, the changes in metabolic and bioenergetic measures imply potential mechanistic factors associated with anthocyanin and proanthocyanidin actions. The demonstration of these benefits in middle-aged individuals with insulin resistance and SCD suggests that ongoing blueberry supplementation may contribute to protection against cognitive decline when implemented early in at-risk individuals.

Keywords: BMI; cognition; insulin resistance.

Figure 1

CONSORT flow diagram showing data concerning participant enrollment, randomized group allocation, completion information, and number of participants included in the group analyses. BB = blueberry treated group.

Figure 2

(A). Lexical access performance by group at enrollment and at the end of the intervention, as measured by the letter form of the Controlled Oral Word Association task. At week 12, the BB group showed improved performance, * F(1,24) = 10.67, p = 0.003, Cohen’s f effect size = 0.66. (B). Recall intrusion errors by group on the California Verbal Learning Test. The BB group exhibited fewer intrusion errors after 12 weeks supplementation, * F(1,24) = 4.69, p = 0.04, Cohen’s f effect size = 0.20. (C). Perceived day-to-day memory difficulties by group as measured by the Everyday Memory Questionnaire, factor 3. The BB group reported a reduction of forgetfulness and encoding-type failures after 12 weeks’ supplementation, * F(1,24) = 4.93, p = 0.03, Cohen’s f effect size = 0.45. (D). Mean fasting insulin values at enrollment and after 12 weeks by group. The BB group showed a reduction of insulin following supplementation, * F(1,24) = 4.62, p = 0.04, Cohen’s f effect size = 0.44. (E). Trend for enhanced mitochondrial uncoupling in peripheral platelets for blueberry-treated participants, # F(1,14) = 2.17, p = 0.11. Error bars = SEM. PL = placebo group. BB = blueberry group. Wk 0 = pre-intervention assessment. Wk 12 = assessment during the final week of the intervention.

Figure 3

Mean daily consumption external to the study for each of the major anthocyanins by group at enrollment and after 12 weeks. There was no between-group difference in consumption and no change relative to pre-intervention levels. Panel (A) shows consumption of delphinidin, malvidin, pelargonidin, peonidin, and petunidin, which were consumed at relatively lower levels. Panel (B) represents cyanidin levels, for which there was considerably greater intake. Note the difference in range of values on the vertical axes between panel (A) and panel (B). Error bars = SEM. PL = placebo group. BB = blueberry group. Wk 0 = pre-intervention assessment. Wk 12 = assessment during the final week of the intervention.