Associations Between Ultra-Processed Food Consumption and Adverse Brain Health Outcomes

Abstract

Background and objectives: Ultra-processed foods (UPFs) are linked to cardiometabolic diseases and neurologic outcomes, such as cognitive decline and stroke. However, it is unclear whether food processing confers neurologic risk independent of dietary pattern information. We aimed to (1) investigate associations between UPFs and incident cognitive impairment and stroke and (2) compare these associations with other commonly recommended dietary patterns in the REasons for Geographic and Racial Differences in Stroke study. This prospective, observational cohort study enrolled Black and White adults in the United States from 2003 to 2007.

Methods: The NOVA system was used to categorize items from a baseline food frequency questionnaire according to the level of processing. Participants with incomplete or implausible self-reported dietary data were excluded. Consumption for each category (grams) was normalized to total grams consumed. Scores quantifying adherence to a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet were also calculated. Incident cognitive impairment was defined using performance relative to a normative sample on memory and fluency assessments. Incident stroke was identified through adjudicated review of medical records.

Results: The cognitive impairment cohort (n = 14,175) included participants without evidence of impairment at baseline who underwent follow-up testing. The stroke cohort (n = 20,243) included participants without a history of stroke. In multivariable Cox proportional hazards models, a 10% increase in relative intake of UPFs was associated with higher risk of cognitive impairment (hazard ratio [HR] = 1.16, 95% CI 1.09-1.24, p = 1.01 × 10^-5) and intake of unprocessed or minimally processed foods with lower risk of cognitive impairment (HR = 0.88, 95% CI 0.83-0.94, p = 1.83 × 10^-4). Greater intake of UPFs (HR = 1.08, 95% CI 1.02-1.14, p = 1.12 × 10^-2) and unprocessed or minimally processed foods (HR = 0.91, 95% CI 0.86-0.95, p = 2.13 × 10^-4) were also associated with risk of stroke in multivariable Cox models. The effect of UPFs on stroke risk was greater among Black than White participants (UPF-by-race interaction HR = 1.15, 95% CI 1.03-1.29, p = 1.50 × 10^-2). Associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean, DASH, and MIND diets.

Discussion: Food processing may be important to brain health in older adults independent of known risk factors and adherence to recommended dietary patterns.

Figure 1. Participant Flow Diagram

Participants in a subgroup of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with self-reported dietary data were divided into separate cohorts to assess incident stroke and cognitive impairment. FFQ = Food Frequency Questionnaire.

Figure 2. Association Between Ultra-Processed Food Intake and Incident Stroke

(A and B) Forest plots demonstrating hazard ratios (HR) and 95% confidence intervals (CI) for stroke risk associated with intake of NOVA1 (unprocessed or minimally processed), NOVA3 (processed), and NOVA4 (ultra-processed) items, along with higher Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet scores. HRs for NOVA categories represent the HR per 10% relative increase in consumption (in % grams/d). HRs for other dietary patterns represent the HR per 1-point increase in score. Forest plots are shown for (A) a base model, adjusted for age, race, sex, total caloric intake, and age-by-race interaction and (B) a fully adjusted model, which also included smoking status, atrial fibrillation, hypertension, diabetes mellitus, cardiovascular disease, and left ventricular hypertrophy. (C) Change in partial log-likelihood associated with adding NOVA1, NOVA3, or NOVA4 intake to reference Cox models that included adherence to a Mediterranean, DASH, or MIND diet and covariates from the fully adjusted model. Points labeled with an asterisk (*) represent significant (p < 0.05) changes from the reference model partial log-likelihood. (D) Change in partial log-likelihood associated with adding adherence to a Mediterranean, DASH, or MIND diet to reference Cox models that included NOVA1, NOVA3, or NOVA4 intake and covariates from the fully adjusted model.

Figure 3. Association Between Ultra-Processed Food Intake and Incident Cognitive Impairment

(A and B) Forest plots demonstrating hazard ratios (HR) and 95% confidence intervals (CI) for the risk of incident cognitive impairment associated with intake of NOVA1 (unprocessed or minimally processed), NOVA3 (processed), and NOVA4 (ultra-processed) items, along with higher Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet scores. HRs for NOVA categories represent the HR per 10% relative increase in consumption (in % grams/d). HRs for other dietary patterns represent the HR per 1-point increase in score. Forest plots are shown for (A) a base model, adjusted for age, race, sex, educational attainment, annual income, and total caloric intake and (B) a fully adjusted model, which also included physical exercise, body mass index category, hypertension, diabetes mellitus, cardiovascular disease, depressive symptoms, alcohol use, and smoking status. (C) Change in partial log-likelihood associated with adding NOVA1 or NOVA4 intake to reference Cox models that included adherence to a Mediterranean, DASH, or MIND diet and covariates from the fully adjusted model. Points labeled with an asterisk (*) represent significant (p < 0.05) changes from the reference model partial log-likelihood. (D) Change in partial log-likelihood associated with adding adherence to a Mediterranean, DASH, or MIND diet to reference Cox models that included NOVA1 or NOVA4 intake and covariates from the fully adjusted model.