Nutritional interventions have become an increasingly attractive solution for slowing inflammatory aging, so called "inflammaging." Cocoa extract has been shown in previous, smaller studies to reduce inflammatory biomarkers, thanks to flavanols -- small, bioactive compounds found not only in the cocoa bean but also berries, grapes, tea, and other plant-based foods. To bridge the gap between these studies and humans, researchers launched the large-scale COSMOS trial, which examines the effects of cocoa extract on cardiovascular disease, and whether inflammaging may explain those effects.

"Our interest in cocoa extract and inflammaging started on the basis of cocoa-related reductions in cardiovascular disease," said corresponding author Howard Sesso, ScD, MPH, associate director of the Division of Preventive Medicine and associate epidemiologist at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system. "We also appreciate the important overlap between healthy aging and cardiovascular health, where aging-related inflammation can harden arteries and lead to cardiovascular disease. Because of that, we wanted to see whether multi-year cocoa extract supplementation versus a placebo could modulate inflammaging -- and the data suggests it does."

Between 2014 and 2020, Brigham and Women's Hospital led the COSMOS trial, a large-scale, randomized, double-blind, placebo-controlled clinical trial with 21,442 participants over 60 years old, finding that cocoa extract supplementation decreased cardiovascular disease mortality by 27%.

In this new study, researchers collected and analyzed blood samples of 598 COSMOS participants to measure several inflammaging biomarkers: three pro-inflammatory proteins (hsCRP, IL-6, and TNF-α), one anti-inflammatory protein (IL-10), and one immune-mediating protein (IFN-γ). Comparing changes in these biomarkers measured at baseline, 1, and 2 years follow-up, hsCRP levels decreased by 8.4% each year compared with placebo, while the other biomarkers remained relatively consistent or increased modestly.

"Interestingly, we also observed an increase in interferon-γ, an immune-related cytokine, which opens new questions for future research," said senior author Yanbin Dong, MD/PhD, Director of the Georgia Prevention Institute (GPI) and cardiologist/population geneticist at the Medical College of Georgia/Augusta University. "While cocoa extract is not a replacement for a healthy lifestyle, these results are encouraging and highlight its potential role in modulatingi nflammation as we age.

The decrease in hsCRP may help explain the cardio-protective effects seen with cocoa extract supplement in the larger COSMOS trial, where participants experienced a reduction in cardiovascular disease death. Researchers said that changes in the other inflammaging markers, including a small reduction in IL-6 observed in female but not male participants, warrant additional study. The team will continue to evaluate the COSMOS trial to determine whether the cocoa -- and multivitamin -- regimens can curb more severe inflammaging, as well as other important aging-related health outcomes.

"This study calls for more attention to the advantage of plant-based foods for cardiovascular health, including cocoa products rich in flavanols," added Sesso. "It reinforces the importance of a diverse, colorful, plant-based diet -- especially in the context of inflammation."

Authorship: In addition to Sesso, Mass General Brigham authors include Sidong Li, Rikuta Hamaya, Allison Clar, Pamela M. Rist, and JoAnn E. Manson. In addition to Dong, Augusta University authors include Haidong Zhu and Ying Huang.

Disclosures: Manson and Sesso received investigator-initiated grants from Mars Edge, a segment of Mars Incorporated dedicated to nutrition research and products, for infrastructure support and donation of COSMOS study pills and packaging, and Pfizer Consumer Healthcare (now Haleon) for donation of COSMOS study pills and packaging during the conduct of the study. Sesso additionally reported receiving investigator-initiated grants from Pure Encapsulations, American Pistachio Growers, and Haleon, and honoraria and/or travel for lectures from the Council for Responsible Nutrition, BASF, Haleon, and NIH during the conduct of the study. No other authors reported any conflicts of interests for this study

Funding: This work is supported by the National Institutes of Health (HL157665). The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of study pills and packaging. Pfizer Consumer Healthcare (now Haleon) provided support through the partial provision of study pills and packaging. COSMOS is also supported in part by the National Institutes of Health (AG050657, AG071611, and EY025623). Neither company had a role in the trial design or conduct, data collection, data analysis, or manuscript preparation or review.

A new Boston University study has a potential answer, suggesting that memories of mundane moments are given extra sticking power if they become connected to a significant event -- something surprising, rewarding, or carrying an emotional punch. Watch your Powerball numbers cash in, for example, and you're likely to remember what you were doing in the moments before, however unremarkable and unmemorable they might have otherwise been. The findings, published in Science Advances, could potentially lead to improved treatments for people with memory problems or even help students retain tricky concepts.

"Memory isn't just a passive recording device: Our brains decide what matters, and emotional events can reach back in time to stabilize fragile memories," says Robert M.G. Reinhart, a BU College of Arts & Sciences associate professor of psychological and brain sciences. "Developing strategies to strengthen useful memories, or weaken harmful ones, is a longstanding goal in cognitive neuroscience. Our study suggests that emotional salience could be harnessed in precise ways to achieve those goals."

In their paper, he and his colleagues give the example of someone hiking through Yellowstone National Park and stumbling across a herd of majestic bison. The wow of that moment, they discovered, would not just cement the one magical experience in the mind, but lots of little, more run-of-the-mill events leading up to and away from it -- a rock spotted on the path, a small animal darting into the undergrowth.

"The question is, What are the mechanisms for that?" says Reinhart, who's also a College of Engineering associate professor of biomedical engineering and a faculty member at the BU Center for Systems Neuroscience. "That's what we tried to uncover, how the brain selectively strengthens those fragile memories."

How the Brain Selects Which Memories to Preserve

While most of us know that special moments get a revered spot in our memory banks, researchers have been divided on concepts known as retroactive and proactive memory enhancement -- the prioritization of memories immediately before or after a big, or salient, event. Previous studies have disagreed on whether or not weaker memories are stabilized, or made easier to recall, by attachment to a more prominent one.

Reinhart says the latest project, which included close to 650 participants, ten individual studies, and the use of artificial intelligence to analyze a broader set of data, is the first to definitively show that memory enhancement does happen. One major difference with past studies: they found the brain uses a sliding scale to decide which memories to preserve. Many of the team's experiments involved showing participants dozens of images -- connected to different levels of rewards -- then giving them a surprise memory test the next day.

With things that occurred after an event, proactive memories, the strength of recall seemed to depend on the emotional impact of the big moment itself -- the more enduring the salient event, the more likely everything after it was to be remembered. That didn't apply when reaching back to the things that happened in the runup, the retroactive memories. They were more likely to be cemented if they had similarities -- perhaps a visual cue, like a matching color -- that connected them to the pivotal event. According to Reinhart, it's the first validation in humans of "graded prioritization, a new principle of how the brain consolidates everyday experiences."

"For the first time, we show clear evidence that the brain rescues weak memories in a graded fashion, guided by their high-level similarity to emotional events," says Chenyang (Leo) Lin (GRS'30), the paper's first author and a doctoral student in the Reinhart Lab. "It's not just timing that matters, but also conceptual overlap."

The researchers also found that if any secondary memories carried emotional weight themselves, the memory enhancement effect was diminished. "The brain seems to prioritize fragile memories that would otherwise slip away," says Reinhart, who has published a series of highly cited papers on how memory functions. Much of his research has also included brain stimulation -- using noninvasive techniques to improve working and long-term memory in older adults or to curb obsessive-compulsive behavior.

Rescuing Memories; Improving Test Scores

Although the latest study was focused on uncovering a basic mechanism guiding how memories are encoded, Reinhart says the work could lay the foundation for future clinical and other real-world studies and interventions.

"The discovery has broad implications for both theory and practice," says Reinhart. "In education, pairing emotionally engaging material with fragile concepts could improve retention. In a clinical setting, we could potentially rescue memories that are weak, way back in the recesses of our mind because of normal aging, for example. You can flip it, too, for people with trauma-related disorders -- maybe you don't want to rescue a distressing memory."

Reinhart's research is funded by the National Institutes of Health, the International Obsessive-Compulsive Disorder Foundation, the AE Research Foundation, and philanthropy.