Artificial sweeteners have long been marketed as a healthier alternative to sugar, but new research suggests they may not be so harmless for brain health. A large, long-term study has found a link between consuming low- and no-calorie sweeteners and cognitive decline, especially in people under 60 years old.

The first-of-its-kind study adds to the body of research suggesting that artificial sweeteners may come with health consequences -- but they also have some benefits, such as being lower in calories, reducing risk of cavities and aiding in blood sugar management.

So what does the new research mean if you regularly consume artificial sweeteners? Here's what to know.

The study followed over 12,000 middle-aged Brazilian adults for eight years, measuring their dietary intake of seven common sweeteners using self-reporting:

"We used the sweeteners that were available in Brazil at the time (of enrollment)," Dr. Claudia Suemoto, associate professor of geriatrics at the University of Sao Paulo and one of the study authors, tells TODAY.com via email. "Unfortunately, some sweeteners, like sucralose and stevia, were not available."

Researchers found that higher intake of the seven sweeteners was significantly associated with declines in global cognition and verbal fluency based on several different cognitive tests. The results were similar among all participants, but the link between low- and no-calorie sweeteners and memory decline was strongest in people with diabetes.

Interestingly, the impact was greater in adults under 60 years old, while no significant associations were seen in those over 60. That suggests dietary habits in midlife, decades before dementia symptoms may appear, could have lifelong consequences for brain health.

"It is important to remember that cognitive performance peaks around the third decade of life, between 25 and 30 years old, and after that there is a very slow, gradual decline in function. What our study shows is that sweetener consumption may accelerate this natural process, even in middle-aged adults," says Suemoto.

The researchers suspect that artificial sweeteners may influence the brain through mechanisms such as neuroinflammation, neurodegeneration or disruption of the gut-brain axis.

"Animal studies, for example, suggest that aspartame can trigger inflammation in the brain, while sugar alcohols like erythritol and sorbitol may alter gut microbes and compromise the blood-brain barrier," says Suemoto.

However, these animal studies used very large doses of sweeteners, beyond what most people consume in a day. So while the results probably do not translate to the smaller doses in beverages and other foods, "more research is needed both in animal models and mostly in humans," Suemoto explains.

While this is the first large cohort study to demonstrate an association between artificial sweeteners and cognitive decline, Suemoto emphasizes that more research is needed.

For example, other studies could look at objective measurements of how much artificial sweetener participants were exposed to and images of the brain to see which parts may be most affected, she adds. Another approach would be to conduct a randomized study where participants either reduce or completely replace artificial sweeteners in their diets.

It's important to note the new study results do not prove causation between artificial sweeteners and cognitive decline, and there are also limitations to how it was conducted, the International Sweeteners Association pointed out in a statement.

"This research is an observational study, which can only show a statistical association, not a direct cause-and-effect relationship," it read in part. "As with all such research, the findings may be influenced by many confounding factors, including overall dietary patterns, lifestyle choices and other health conditions."

The group also took issue with inconsistencies in results across age groups and diabetes status, as well as participants self-reporting their sweetener consumption across several years.

The U.S. Food & Drug Administration (FDA) has also deemed these types of sweeteners safe for human consumption, based on the "available scientific evidence."

But if you're looking for guidance based the data from the new study, Suemoto says moderation is key: "It is wise to limit consumption as much as possible, ideally avoiding daily use."

Artificial sweeteners are found in a wide range of ultraprocessed foods and beverages, including:

Research shows the best strategy for protecting your brain as you age is focusing on an overall diet rich in whole, plant-based foods, like colorful fruits, leafy greens, nuts, whole grains and legumes.

Certain nutrients, like healthy fats, antioxidants, carotenoids, vitamin E and choline, are particularly beneficial for reducing inflammation and promoting brain health over time.

If you're reaching for sugar substitutes every day, here are some small, brain-friendly swaps you can try: