ATLANTA — Daily consumption of pomegranate juice may protect memory in older, physically healthy people, new research suggests. Early results from a randomized trial of more than 200 participants showed that the group receiving pomegranate juice scored higher on the Brief Visuospatial Memory Test-Revised (BVMT-R) over 12 months than their counterparts who received a placebo drink. "It's encouraging that this safe antioxidant nutrient beverage could have a meaningful impact in delaying visual memory decline associated with aging," said Gary Small, MD, director of the University of California Los Angeles (UCLA) Longevity Center, and professor of psychiatry and biobehavioral sciences at the UCLA School of Medicine. The findings were presented here at the American Association for Geriatric Psychiatry (AAGP) 2019 Annual Meeting. Dementia on the Rise Approximately 6 million Americans have dementia and the prevalence is increasing, Small told conference delegates. An estimated 1 million people in the US have mild cognitive impairment (MCI) and about 110 million older adults who are aging normally have some kind of cognitive complaint, he added. Memory continues to decline as individuals age, with the downward slope depending on genetic makeup and lifestyle factors. There are no disease-modifying treatments for age-related memory loss. Up to half of all Alzheimer's Disease cases worldwide are potentially attributable to seven major risk factors: depression/stress, obesity, hypertension, diabetes, physical inactivity, smoking, and low education/cognitive inactivity. "Some studies suggest that lifestyle factors are even more important than genetic factors, and one of those major areas is nutrition," Small said. Research on pomegranates has been going on for some time now. It started with animal studies that showed that pomegranates and other berries have a positive effect on memory. In 2013, Small and colleagues published a double-blind study of pomegranate juice in 32 middle-aged or older participants with normal aging or MCI. They were randomly assigned to drink pomegranate juice or a placebo drink. Among the 28 individuals who completed the trial, visual memory improved in the juice drinkers. In these participants, functional MRI also showed activation of neuro circuits that control visual memory. Although those results were encouraging, the study was relatively small and continued for only a month. "We wanted to understand this better," and subsequently planned another study, said Small. 8 Ounces Every Day The new study also had a randomized, double-blind design — but it was larger (enrolling 261 participants) and longer (it continued for 1 year). Participants were 50 to 75 years old (mean age, about 60 years) and two thirds were women. They represented a wide range of cognitive abilities. All were randomly assigned to drink 8 ounces of either pomegranate juice every day or a drink that was similar to the pomegranate juice but contained no polyphenols (placebo group). There were no significant differences between the groups in terms of age, sex, proportion with MCI, levels of mild depressive symptoms, history of dementia, or APOE gene carrier status. However, the pomegranate group had slightly more education than the placebo group; the researchers, however, controlled for this in the statistical analysis. Researchers looked at two main outcome measures: the BVMT-R and the Buschke Selective Reminding Test (SRT). The BVMT-R measures visual learning and retention. Participants are presented with six geometric designs in a particular array and get 1 point for correctly placed or drawn responses. On this test, there are three different scores: learning score (how individuals benefit from repetition), total recall score (number of designs recalled over 3 learning trials), and delayed recall score (number of designs recalled after 25 minutes). For the SRT, participants are presented with 12 words that they try to recall on their own, and then with prompts. This test has three different scores: consistent long-term retrieval score, total recall score, and long-term storage score. Mechanism Unclear Of the 261 individuals who were part of the randomization process, 61 did not finish the trial. Results showed a significant group-by-time interaction for the BVMT-R learning score (P = .003). "Basically, what happened was that the pomegranate-juice group maintained a certain level, but the placebo group declined; and the between-group effect size was moderate at 0.45," said Small. He also presented a graph charting the mean BVMT-R visual memory learning score over 12 months. "If you look at the percent change in the learning score, you can see there's about a 26% drop in the placebo group versus a 14% increase in the pomegranate juice group," he said. Changes in other BVMT-R scores and on SRT measures were not significantly different between the groups. There are numerous theories about how pomegranate juice might impact memory, including that it could have a direct effect on the central nervous system — or the effect could be through the gut microbiome. Small noted that animal studies suggest microbiome population shifts could impact memory and learning, and gut bacteria breaks down pomegranate polyphenols to produce urolithins, which cross the blood–brain barrier. In addition to antioxidant effects, pomegranates have anti-inflammatory effects and can have anti-amyloid effects, said Small. "The bottom line is we don't know exactly what's going on, but we have some hypotheses that could explain it," he said. Potential Limitations A limitation of the study is that the participants were not a representative sample of the general population. As well, only 26% of the screened volunteers were actually included in the study. "So we have a motivated, educated, physically healthy group of subjects with age-related memory concerns," Small said. The investigators found a significant between-group difference in only one memory measure that was examined. "One could argue this was a spurious result," Small noted. "Given the high bar for statistical analysis, that's probably unlikely." The "conservative statistical strategy" the researchers used corrected for multiple comparisons and was one of the study's strengths, said Small. He added that certain drugs, such as COX-2 inhibitors, also have anti-inflammatory effects. "But studies have found that if you treat patients who already have dementia with an anti-inflammatory drug, it could actually accelerate cognitive decline." Antioxidant Ceiling? Following the presentation, a meeting attendee asked if there's an antioxidant "ceiling" beyond which there's no further benefit. "If you plot the effects of most drugs or interventions, you will get an inverted U shape curve," said Small. "We don't know what that ceiling is here." The "challenge" with nutritional research is that it's difficult to get funding to do the appropriate dose-finding analyses, he added. Another delegate commented on the expense of daily consumption of pomegranate juice. "Cost is an issue, but this is a problem whether we're talking about supplements, drugs, even diagnostic tools like PET [positron emission tomography] scanning," said Small. "But as these things are used more often, the costs usually come down." Queried about how healthy the diets of the participants were at baseline, Small said the researchers did not take careful dietary histories; he noted, however, that individuals in the study were likely relatively healthy. "Anyone interested in a study like this one is going to be college educated and know about healthy lifestyles," he said. As this was not a representative sample, "one might conclude that healthier people who drink pomegranate juice may get a benefit," he added. Small noted that pomegranate juice is safe, with only a few people in the study reporting stomach issues from drinking it, and is widely available. The researchers received support from the National Institutes of Health, Foundations (Ahmanson, Archstone, Brewster, Dana, Hillblom); Endowments (Elgart, Stark, Parlow-Solomon, Plott); and Pom Wonderful. American Association for Geriatric Psychiatry (AAGP) 2019 Annual Meeting: Session 02. Presented March 4, 2019. Source
