Effects of Walnuts on Postprandial Cognitive Function in Adults With Subjective Cognitive Impairment: Protocol for a...

Subjective cognitive impairment (SCI), the earliest sign of cognitive decline, affects 1 in 9 Americans aged older than 45 years. It negatively affects quality of life and is a risk factor for dementia. Healthy eating is a primary preventative strategy to impede cognitive decline. In the short term, cognitive function may be impacted by the consumption of a single meal, suggesting that the meal components, and not solely the metabolic dysregulation resulting from the condition of obesity, can impact cognition. The effect of meals on postprandial cognitive function is influenced by their macronutrient composition. A meal with a low-quality fat composition can acutely impair postprandial cognitive function. Walnuts are a source of high-quality fat as well as polyphenols. Some randomized control trials have shown that walnuts may benefit cognitive function. However, it is not clear whether a single meal high in walnuts can improve cognition in adults with SCI.

The primary objective of the Essential Fats for Enhancing Cognitive Thinking study is to determine the impact of walnuts on postprandial cognitive function in adults with SCI. Secondary objectives include assessing the impact of daily walnut consumption for 1 week on cognitive function and erythrocyte fatty acids. Exploratory objectives include understanding the effect of walnut consumption on microbiota and intestinal inflammation.

In this 7-week single-blind randomized crossover design study, 78 adults with SCI consumed 1 study snack per day, consisting of walnuts or a chocolate-style snack for 1 week, with a 4-week washout period between. Before consuming each study snack, participants underwent a meal challenge that included this study's snack. Before randomization, participants completed a 1-week run-in period to become acclimated to consuming 1 study snack per day. A registered dietitian nutritionist counseled participants on incorporating this study's snack into their diet while maintaining their body weight. Participants were blinded to which snack was the treatment and which was the control. Dietary intake and physical activity were measured with 24-hour recalls. Cognitive function was measured using the National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function Cognitive Battery, both pre- and postprandially, as well as after 1 week of study snack consumption. Stool samples were collected weekly, except during the washout period, to measure microbiota α-diversity, β-diversity, and butyrate. Additionally, fasting blood samples, weight, and waist circumference were obtained at each study visit.

Recruitment began in February of 2024 and was completed by May 31, 2025.

Improving cognition through the consumption of walnuts may ultimately prove to be an effective way to mitigate SCI.

ClinicalTrials.gov NCT06223672; https://clinicaltrials.gov/study/NCT06223672.

DERR1-10.2196/82032.