Effects of Walnuts on Postprandial Cognitive Function in Adults with Subjective Cognitive Impairment: Protocol for a Randomized Crossover Trial (Preprint)

BACKGROUND Subjective cognitive impairment, the earliest sign of cognitive decline, affects one in nine Americans over age 45. 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 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 subjective cognitive impairment. OBJECTIVE The primary objective of the Essential Fats For Enhancing Cognitive Thinking (EFFECT) study is to determine the impact of walnuts on postprandial cognitive function in adults with subjective cognitive impairment. Secondary objectives include assessing the impact of daily walnut consumption for one week on cognitive function and erythrocyte fatty acids. Exploratory objectives include understanding the effect of walnut consumption on microbiota and intestinal inflammation. METHODS In this 7-week single-blind randomized crossover design study, 78 adults with subjective cognitive impairment will consume 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 will undergo a meal challenge that includes the study snack. Prior to randomization, participants will complete a 1-week run-in period to become acclimated to consuming 1 study snack per day. A registered dietitian nutritionist will counsel participants on incorporating the study snack into their diet while maintaining their body weight. Participants will be blinded to which snack is the treatment and which is the control. Dietary intake and physical activity will be measured with 24-hour recalls. Cognitive function will be 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 will be collected weekly, except during the washout period, to measure microbiota α-diversity, β-diversity and butyrate. Additionally, fasting blood samples, weight, and waist circumference will be obtained at each study visit. RESULTS Recruitment began in February of 2024 and will be completed by July 31, 2025. CONCLUSIONS Improving cognition through consumption of walnuts may ultimately prove to be an effective way to mitigate subjective cognitive impairment. CLINICALTRIAL ClinicalTrials.gov NCT06223672; https://clinicaltrials.gov/study/NCT06223672