JAMA sub-issue: Ultra-processed food hurts the brain! A prospective cohort study followed for 8 years showed that a high intake of ultra-processed foods was associated with a 28% increase in the rate of cognitive decline

At present, the efficacy of dementia treatment is still relatively limited, so it is necessary to continue to find effective measures that can prevent or delay the onset of dementia [1].

Over the past 40 years, the food supply industry has increased the commoditization of ultra-processed foods (UPFs), which account for a gradual increase in total caloric intake[2].

UPFs intake is known to be associated with an increased risk of chronic noncommunicable diseases such as cardiovascular disease and metabolic syndrome [3-4], but the relationship between UPFs and cognitive decline remains to be explored
.

Recently, a research team led by Dr.
Natalia Gomes Gonçalves of the Department of Pathology, Faculty of Medicine, University of São Paulo, Brazil, published an important finding in the prestigious journal JAMA Neurology [4].

The researchers analyzed data from 10,775 civil servants in 6 cities in Brazil and followed up for about 8 years and found that the overall rate of cognitive decline in the group with higher UPF intake was significantly increased by 28% compared with those with UPFs intake in the first quartile (β=-0.
004; 95% CI:（-0.
006, -0.
001）; P=0.
003), while the rate of decline of executive function increased significantly by 25% (β=-0.
003; 95% CI:（-0.
005, 0.
000）; P=0.
01）
。

The results of this large, multicenter prospective cohort study suggest that higher UPFs intake as a proportion of total caloric intake is associated with
cognitive decline.
Despite the small effect size, global cognitive decline is a key indicator of aging, so the findings are still important for preventing cognitive decline and further support current public health recommendations
for limiting UPFs intake.

Article title map

So how did the study work?

The study relied on the Brazilian Longitudinal Research Project on Adult Health (ELSA-Brasil) and recruited 15,105 civil servants
from six Brazilian cities (Belo Horizonte, Porto Alegre, Rio de Janeiro, Salvador, São Paulo and Victoria).
On this basis, a total of 10,775 people were included in the analysis
after excluding participants with no dietary data at baseline from 2008–2010, extreme energy intake (< 600 kcal/day or >6000 kcal/day), missing cognitive tests or covariate data, or reporting taking drugs that negatively affected cognitive performance.
Since then, follow-up has been followed up approximately every 4 years, and a total of 3 survey data have been obtained, as follows:

Study populations were included in the exclusion flowchart

The study collected the dietary status
of participants at baseline through a Food Frequency Questionnaire (FFQ).
FFQ contains a total of 114 food categories, which are grouped into 3 groups according to the Nova classification system: (1) unprocessed or lightly processed food and processed cooking ingredients; (2) processed food; （3）UPFs
。

The daily energy intake value is obtained by adding the energy value (kcal) corresponding to each food in each group, and then calculating the percentage
of UPFs in it.
This relative value not only reflects the proportion of UPFs that make up the participants' diets, but also takes into account individual differences
in caloric intake.
Based on the quartiles, the researchers divided UPFs into the following four groups as a percentage of daily energy intake: 0%-19.
9%, 20.
0%-26.
7%, 26.
8%-34.
1%, and 34.
2%-72.
7%.

At baseline, the average age of participants was 51.
6 (8.
9) years and total daily caloric intake was 2856 (992) kcal, of which 27% came from UPFs
.
Participants in the fourth quartile were more likely to be young, female, white, have higher education and income, were more likely to be nonsmokers, and less likely to be current drinkers
than the first quartile of UPFs' daily energy generation.
The highest quartile also had higher total energy intake, less exercise, and a higher proportion
of depressive symptoms.

Basic facts of the study population

For cognitive function, the researchers measured
memory (immediate recall, delayed recall and word recognition tests) and executive function (verbal fluency test and B version connection test).
The z-score for analysis is obtained by subtracting the average of the wave 1 score from the scores of wave 2 and wave 3 and dividing the resulting difference by the standard deviation of the wave 1 score
.

This study used a linear mixed-effects model to assess the relationship between the proportion of daily intake of UPFs at baseline and changes in cognitive ability over time, and calculated the percentage of cognitive decline: the slope of each quartile minus the slope of the first quartile, and then divide this difference by the slope of the first quartile and multiply by 100
.

The results of the analysis showed that more than 19.
9% of participants (including the second to fourth percentile) had a 28% faster rate of global cognitive decline (β=-0.
004; 95% CI=(-0.
006, -0.
001);P=0.
003) and 25% faster (β = -0.
003, 95% CI=(-0.
005, 0.
000);P=) compared with the first quartile of UPFs with a daily intake of 19.
9% or less 0.
01）
。

The researchers also found that for participants under 60 years of age, participants with a daily intake of UPFs greater than 19.
9% showed faster overall cognitive decline (β = -0.
006; 95% CI=(-0.
009,-0.
003);P < 0.
001).

For people age 60 or older, the percentage of daily energy intake of UPFs was not associated
with overall cognitive decline.

Association between baseline daily intake of UPFs and cognitive decline

In addition, adherence to a healthy diet is another modifier associated with UPFs with overall cognitive function
.
The results of the study found that participants with low healthy eating scores who consumed more than 19.
9% of calories from UPFs experienced a faster decline in overall cognitive performance (β = -0.
005; 95% CI=（-0.
009，-0.
002）; P = 0.
004）
。 Among participants with high scores on healthy eating, there was no association
between percentage energy intake from UPFs and overall cognitive function.

Association between daily intake of UPFs and overall cognitive decline among participants with low and high healthy eating scores

In the sensitivity analysis, the researchers excluded participants with calorie intake above the 95th percentile, but no longer excluded extreme cases of energy intake, in addition to using the cognitive score of wave 3 to estimate cognitive performance data for participants under 55 in wave 2, all similar to those in the main analysis
.

In summary, the results of this large cohort study from low- and middle-income countries with long follow-up suggest that limiting the intake of UPFs, particularly in middle-aged people, may be an effective form of
preventing cognitive decline.
Notably, the study included middle-aged people, which is important
for understanding potential prevention targets for cognitive decline early in life.

However, there are several limitations
to consider when interpreting the results.
First, diets are only assessed at baseline, which may be difficult to reflect longitudinal dietary changes and lead to underestimation of the association between UPFs intake and cognition; Second, FFQs are not specifically a tool for assessing the degree of food processing, which may lead to misclassification, and FFQs are obtained through self-reporting, and consumption of UPFs may be underreported due to social expectation bias, which may make the association bias invalid; In addition, due to the lack of neuroimaging data in the ELSA-Brasil study, it is impossible to further explain the possible mechanism behind the association between increased UPFs intake and cognitive decline, which requires more research to further explore and elucidate
.

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