Abstract
Background/Objectives: Nutrients such as vitamin B12, folate (B9), and polyunsaturated fatty acids (PUFAs) may independently influence cognitive health, but their combined effects and interactions remain unclear. This study aims to investigate the effects of B12, folate, and PUFAs, including their interactions, on cognitive function in cognitively healthy older adults, considering effect modification by sex and amyloid-beta status. Methods: A cross-sectional analysis was conducted using data from 321 participants aged 60-85 y enrolled in the UK CHARIOT-PRO SubStudy. Dietary intake was assessed using the Scottish Collaborative Group Food Frequency Questionnaire, and cognitive performance was measured via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Stratified multivariate linear regression models by sex and amyloid-beta status and models with the saturated to unsaturated fatty acid ratio (substituted for PUFAs) as one of the predictors were constructed. Results: Males had lower total RBANS scores with a higher PUFA intake (β = -13.97, p = 0.04) but improved scores with increased folate (β = 9.08, p = 0.04). PUFA × folate revealed contrasting effects to PUFAs alone, with higher cognitive scores in the amyloid-negative group for total RBANS (β = 13.27, 95%: 3.81~22.73, p = 0.01) but lowered scores in the amyloid-positive group. Considering the UFA:SFA ratio, higher delayed memory scores were associated with the combined intake of folate, B12, and PUFAs (β = 7.46, p = 0.02) among females. In the amyloid-positive group, the negative cognitive effects observed with PUFAs were reversed when UFA:SFA was considered. Conclusions: Amyloid status and sex significantly influenced the cognitive effects of nutrient intake, with distinct patterns based on specific cognitive domains and nutrient interactions.