The Neuroscientist Comments.

The progressive aging of population, linked to higher life expectancy, observed worldwide in the past decades, determined an increase in the prevalence of dementia in people aged 65 and higher. Data from the Global Burden of Disease 2019 show that the prevalence of the disease is estimated to increase from 57 million cases (in 2019) to 153 million (in 2050). Currently, there is no effective treatment that may significantly modify the course of dementia. Brain pathologic changes seem to initiate long before clinical manifestations, which mostly occur in old age. This provides a large time window to implement prevention strategies that might effectively delay age-related cognitive decline and dementia. Accumulating evidence supports the view that lifestyle modifications, such as physical activity, smoking cessation, and healthy dietary habits, can play a key role in dementia prevention. As for the latter, interest in dietary and nutritional components as potential modifiable factors for postponing the onset and severity of age-related deterioration of cognitive function has grown in recent decades. Within this scenario, the important role of the industrial processing of foods is being increasingly recognized, particularly the contribution of ultra-processed food (UPF). UPFs are industrial formulations of processed food substances (oils, fats, sugars, starch, and protein isolates) that contain little or no whole food and typically have flavorings, colorings, emulsifiers, and other “cosmetic” additives. UPFs are becoming dominant in diets globally and are replacing traditional diets based on unprocessed and/or minimally processed foods. UPF consumption has been associated with overall decline in the nutritional quality of diets, as well as with several chronic diseases such as overweight/obesity, metabolic syndrome, hypertension, diabetes, and cardiovascular diseases, which in turn contribute to cognitive decline onset. In a very recent study, Gomes Gonçlaves and others (2022) published the findings from the Brazilian Longitudinal Study of Adult Health, a multicenter cohort study that comprises public servants aged 35 to 74 years at baseline from six Brazilian cities (Belo Horizonte, Porto Alegre, Rio de Janeiro, Salvador, São Paulo, and Vitoria). Data were collected in three waves, approximately four years apart, starting in 2008 to 2010. The second wave took place in 2012 to 2014, and the third wave was in 2017 to 2019. Data from 10,775 participants were analyzed. The mean age at the baseline was 51.6 years; 5880 participants (54.6%) were women, 5723 (53.1%) were white, and 6106 (56.6%) had at least a college degree. Results showed that consumption of UPF greater than 19.9% of daily calories was predictive of a faster decline in global cognitive performance and executive function. Moreover, the percentage of daily energy from UPF was associated with cognitive decline in participants with a low healthy diet core only, since no correlation was found for those with high healthy diet scores. Food and drink consumption in the past 12 months was assessed at baseline using a validated Food Frequency Questionnaire (FFQ) with 114 items. Foods were classified according to the extent of industrial processing using the Nova classification system, including three groups of food: unprocessed or minimally processed foods and processed culinary ingredients (Nova groups 1 and 2), processed foods (Nova group 3) and UPFs (Nova group 4). Consumption of UPF was then expressed as a percentage of total daily energy consumption and grouped into quartiles (0%–19.9%, 20.0%–26.7%, 26.8%–34.1%, 34.2%–72.7%). From a cognitive perspective, the memory domain included the immediate recall, late recall, and recognition word list tests from the Consortium to Establish a Registry for Alzheimer Disease, while the executive function domain included semantic and phonemic verbal fluency tests and the TrailMaking Test B version. Although no overall association between percentage of daily energy from UPF and memory score was found, the authors found that age was a modifier for the association between percentage of daily energy from UPF and cognitive function, as those who were younger than 60 years with UPF consumption greater than 19.9% showed faster global cognitive decline than those who consumed less than that amount. Adhesion to a healthy diet was also a modifier of cognitive decline, as individuals with low healthy diet scores who consumed more than the lowest quartile of calories from UPF showed a faster global cognition decline than those who consumed less than 19.9%. Notably, there was no association between the percentage of daily energy from UPF and global cognition for those with high healthy diet scores. The study investigators concluded that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline. Future studies investigating the mechanism by which UPF may lead to cognitive decline are needed, as well as confirmation of our findings in other longitudinal studies and randomized clinical trials.” However, authors do not provide strong insights into the possible mechanisms at the foundation of the reported associations. In this regard, it has been suggested that UPF consumption may have potential effects on metabolism and health through the modulation of gut microbiota composition and function. In fact, there is growing evidence demonstrating that diet may have an effect on cardiovascular risk factors and metabolism through gut microbiota modulation, since food processing alters the provision of macronutrient substrate to the colon due to factors that