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

Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex‐associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease. Methods and Results: Targeted metabolomics was conducted for 357 metabolites in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) case‐cohort substudy for incident stroke. Weighted logistic regression models were used to identify metabolites associated with sex in REGARDS. Sex‐associated metabolites were replicated in the HyperGEN (Hypertension Genetic Epidemiology Network) and using the literature. Weighted Cox proportional hazard models were used to evaluate associations between metabolites and incident stroke. Cox proportional hazard models were used to evaluate associations between metabolites and incident coronary heart disease. Weighted logistic regression models were used to evaluate associations between metabolites and hypertension and chronic kidney disease. Fifty‐one replicated metabolites were associated with sex. Higher levels of 6 phosphatidylethanolamines were associated with incident stroke. No metabolites were associated with incident coronary heart disease. Higher levels of uric acid and leucine and lower levels of a lysophosphatidylcholine were associated with hypertension. Higher levels of indole‐3‐lactic acid, 7 phosphatidylethanolamines, and uric acid, and lower levels of betaine and bilirubin were associated with chronic kidney disease. Conclusions: These findings suggest that the sexual dimorphism of the metabolome may contribute to sex differences in stroke, hypertension, and chronic kidney disease.