Köbe T, Witte AV, Schnelle A, et al. Impact of resveratrol on glucose control, hippocampal structure and connectivity, and memory performance in patients with mild cognitive impairment. Front Neurosci. 2017;11:105. doi: 10.3389/fnins.2017.00105.
Mild cognitive impairment (MCI) is a symptom associated with aging, dementia, and Alzheimer's disease. Nutrition and plant phytochemicals have been recognized as factors that can influence brain structure, function, and cognition. In vivo studies have shown that the polyphenol resveratrol, commonly found in grapes (Vitis vinifera, Vitaceae) and wine, may have neuroprotective effects. Preliminary studies in healthy humans showed resveratrol increased cerebral blood flow, glucose control, and memory performance. According to the authors, the effect of resveratrol has not been evaluated in patients with MCI. Hence, the purpose of this proof-of-concept, randomized, double-blind, placebo-controlled study was to evaluate the effect of resveratrol in patients with MCI.
Patients (n = 42, aged 50-80 years) diagnosed with MCI according to Mayo criteria within 12 months of study entry were recruited from the Memory Clinic of the Department of Neurology of the Charité University Hospital and Neurology specialist practice in Berlin, Germany, and from the Institute of General Practice in Frankfurt am Main, Germany. Included patients had "relatively preserved general cognition, no impairment in activities of daily living, and no dementia." Excluded patients had a mini-mental state exam score <24 at baseline; had severe untreated medical, neurological, or psychiatric diseases and brain pathologies identified with magnetic resonance imaging (MRI) scan; had "no right-handedness"; were non-fluent in German; and had a body mass index of <18 kg/m2 or >35 kg/m2.
For 26 weeks, patients received either 200 mg/day resveratrol plus 350 mg quercetin (VIA Vitamine; Oberhausen, Germany) or 1015 mg/day olive (Olea europaea, Oleaceae) fruit oil capsule (VIA Vitamine) as control. Quercetin was added to the resveratrol treatment to increase bioavailability of resveratrol. Patients were instructed to maintain their normal diet and exercise routine. At baseline and study end, learning and episodic declarative memory performance was evaluated with the Rey Auditory Verbal Learning Test; the change in total brain gray matter volume, hippocampus volume, and hippocampal resting-state functional connectivity (RSFC) was assessed via MRI; and glucose control was measured via blood sampling.
At baseline, demographic characteristics were similar between groups. However, the control group had more patients who were apolipoprotein E (APOE) e4 carriers and who had higher levels of high-sensitivity C-reactive protein. There was no significant change from baseline in memory performance, even after adjusting for age, sex, APOE status, and education. There was a significant decrease in glycated hemoglobin (HbA1c), a long-term measure of glucose control, in the resveratrol group (P = 0.005) but not in the control group. However, the difference in the change in HbA1c was not significantly different between groups. There was no significant change in glucose or insulin in either group. Resveratrol significantly increased RSFC between the right hippocampus and the right angular cortex compared with placebo (P < 0.001). The result did not change when adjusted for age, sex, APOE status, or correction for multiple comparisons. The decrease in HbA1c did not correlate with the increase in RSFC. At baseline, there was no significant difference between groups in gray matter or hippocampus volume. Patients in the control group had a 4.2% decrease in left anterior hippocampal volume, while there was no change in the resveratrol group. However, the difference between groups was not statistically significant. There were no significant changes in other hippocampal regions or in gray matter volume between groups.
The authors conclude that "these findings support resveratrol as a potential non-pharmacological agent to modify the disease process in MCI patients." The authors hypothesize that despite the effect of resveratrol on RSFC, there were no "downstream" cognitive effects because of the small sample size and/or short treatment duration. A limitation of the study is that the effects attributed to resveratrol may have also been influenced by quercetin. However, quercetin is not known to affect cognition. Finally, the authors could be biased; the data are not sufficiently robust to support the authors' conclusions. At best, the conclusion is that preliminary evidence supports a possible benefit of resveratrol in patients with MCI, but additional research is needed. The authors declare no conflict of interest.—Heather S. Oliff, PhD