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The consumption of ultra-processed foods has long been associated with metabolic diseases such as obesity, metabolic syndrome, and type II diabetes. More recent studies have shed light on the connection between ultra-processed foods and cognitive decline, providing an enhanced understanding of the effects that highly processed foods have on overall health and longevity, both in a physical and psychological manner. The proposed mechanism of action for this correlation involves the brain gut microbiome system, in which complex communication pathways among gut bacteria, the gut lining, the vagus nerve, the brain, and systemic circulation affect neuroinflammation and neurodegeneration both of which are highly associated with cognitive decline.

“Ultra-processed foods differ from minimally or regularly processed foods by the addition of substances such as flavors, colors, sweeteners, and emulsifiers, as well as a large percentage of sugars and fats.”

Ultra-processed foods are formulations of mostly artificial and unnatural food substances that have gone through rigorous processing and typically include large percentages of sugars, oils, fats, starch, flavorings, emulsifiers, and other cosmetic additives. The Nova classification system is used to arrange foods into four different groups depending on the level of processing and ranges from unprocessed or minimally processed foods (fresh vegetables, fruits, grains, etc.) to ultra-processed foods (chips, cookies, frozen foods, etc.). Importantly, ultra-processed foods differ from minimally or regularly processed foods by the addition of chemicals such as artificial flavors, colors, sweeteners, and emulsifiers, as well as a large percentage of sugars and fats, which normally wouldn’t be found in home-cooked food. These additives are often used to increase shelf life or enhance texture, consistency, or palatability of the food, yet many of them have been found to have negative effects on the gut microbiome and overall health. Another one of the dangers of ultra-processed foods is that they often constitute a mixture of sugar, fat, and refined starch that can promote and create food addiction and hence overconsumption. Converging evidence from large-scale studies, has found a direct correlation between the consumption of ultra-processed foods and low-grade systemic inflammation, as well as gut dysbiosis. Other studies focused on clinical pathology found an association with metabolic syndrome, type II diabetes, obesity, as well as brain disorders such as depression and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease.

“The researchers found decreased performance in a cognitive exam testing for language and executive function in individuals with higher ultra-processed food consumption.”

In fact, the association of low-quality, highly processed diets and neurodegeneration has been a hot topic of recent research, which has suggested a direct link between the two. A very recent study published in the journal JAMA investigated 10,775 individuals over an average span of 8 years and found a direct association between higher consumption of ultra-processed foods and a higher rate of cognitive decline, both regarding global and executive functioning. Another study published last year looked at the association between the consumption of ultra-processed foods and cognitive performance in older adults. The researchers found decreased performance in a cognitive exam testing for language and executive function in individuals with higher ultra-processed food consumption. Another recent study published in the journal Oxford Academic examined the same association of ultra-processed food intake and cognitive decline, this time in older patients with type II diabetes, and found that increased consumption of such a diet was associated with a higher rate of cognitive decline, in both global and executive aspects. All these findings from well-controlled, large-scale studies suggest that a high consumption of ultra-processed foods may create cognitive decline in older age, though large-scale, high-quality studies of causation have yet to be carried out.

“The low-grade systemic inflammatory state that is known to be caused by gut dysbiosis as an effect of a poor-quality diet high in simple sugars and saturated fats, as well as low in fiber, nutrients, and gut-healthy polyphenols is directly associated with neuroinflammation.”

Targeting the underlying pathways of these associations between ultra-processed food intake and cognitive decline, several studies have investigated the effects of consumption of highly processed foods on the brain gut microbiome system and found variations in both composition and diversity of important gut microbiota, correlating with increased risk of metabolic and brain disease.

The intake of ultra-processed food is generally associated with a reduced intake of plant derived healthy food components such as fiber, vitamins, polyphenols, and minerals, combined with an increased intake of sugar and saturated fat which have been associated with a reduced diversity of the gut microbiome and a reduced prevalence of short chain fatty acid producing microbial species. This reduction in the anti-inflammatory effects of butyrate is likely to contribute to the low-grade systemic inflammatory state, which is characterized by high levels of endotoxins (such as LPS), free fatty acids, and inflammatory mediators (such as IL-B, TNF-a, and IL-6). Such a systemic dysregulation of the immune system may negatively affect multiple organs and tissues, including adipose tissue, the vascular system, the liver and the brain, the latter being a risk factor for vulnerable individuals to develop early cognitive decline, Alzheimer’s disease and Parkinson’s disease.

“A systematic review and meta-analysis looking at nine different cohort studies …found that the highest Mediterranean diet score…had an inverse association with the development of cognitive decline.”

On the other hand, a Mediterranean-style diet has been associated with gut microbiome changes that suggest decreased risk for cognitive decline. Several large-scale studies looked at changes in the gut microbiome as a result of adherence to a Mediterranean-style diet and found increases in the bacteria that are associated with decreases in systemic inflammation, enhanced brain health, and decreased risk for cognitive decline. A systematic review and meta-analysis looking at nine different cohort studies with a total of 34,168 participants found that the highest Mediterranean diet score, summarized from all studies, had an inverse association with the development of cognitive decline. This, and converging evidence from large-scale studies such as the Nu-Age study, suggest that high adherence to a Mediterranean-style diet may decrease the risk for conditions of cognitive decline. Given the extensive literature about the relationship of the gut microbiome changes (in particular reduction of butyrate producing species) and their effects on systemic inflammation and brain health, it is likely that the gut microbiome plays an important role in the association of ultra-processed food intake and increased risk for cognitive decline.

“Minimizing one’s consumption of processed foods, and especially ultra-processed foods will be the first step toward improved metabolic health and decreased risk for neurodegeneration.”

In conclusion, the intake of ultra-processed food is highly associated with greater risk and development of cognitive decline. To decrease the risk for development of dementia and other neurodegenerative conditions, it is hence best to cultivate a healthy gut microbiome by following a largely plant based diet high in fiber, nutrients, vitamins, and polyphenols. Such a diet is constituted by high intake of vegetables, fruit (especially berries), whole grains, extra virgin olive oil, fresh nuts, and other (preferably organic) whole foods. Minimizing one’s consumption of processed foods, and especially ultra-processed foods will be the first step toward improved metabolic health and decreased risk for neurodegeneration. Other lifestyle factors associated with enhanced brain health and cognition include regular exercise, sufficient high-quality sleep (hyperlink to Fiona Riddle’s article in this issue), stress management, and meaningful social connections.