AUTHOR=Wang Lijing , Liu Kuo , Zhang Xiaona , Wang Yushan , Liu Wen , Wang Tao , Hao Ling , Ju Mengwei , Xiao Rong TITLE=The Effect and Mechanism of Cholesterol and Vitamin B12 on Multi-Domain Cognitive Function: A Prospective Study on Chinese Middle-Aged and Older Adults JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 13 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.707958 DOI=10.3389/fnagi.2021.707958 ISSN=1663-4365 ABSTRACT=Background: Nutrients were associated with cognitive function, but limited researches have systematically evaluated on multi-domain cognitive function. The aim of the current study was to investigate the effect and mechanism of specific nutrient on multi-domain cognitive function, and provide nutrition guidance for improving cognitive function. Methods: Participants were selected based on a multicenter prospective study among middle-aged and older adults in China. Global cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Nutrients intake was assessed according to food frequency questionnaire and China Food Composition Database, and principal component analysis was used to extracted nutrient patterns. The associations between specific nutrients and cognitive function were assessed using log-binomial regression. Restricted cubic spline was used to illustrate dose-response relation of nutrients on multi-domain cognitive function. Mediation analysis was used to determine the mechanism of nutrients on cognitive function. Results: Four nutrient patterns were identified (Vitamin-Mineral, Protein-Carbohydrate, Fatty Acid-Vitamin E, Cholesterol-Vitamin B12), and only nutrient pattern rich in cholesterol and vitamin B12 was found associated with cognitive function (RR = 0.891,95%CI = 0.794-0.999). In multi-domain cognitive function, dietary cholesterol and vitamin B12 were related to better performance of visual memory function (P = 0.034, P = 0.020). In dose-response relation, it suggested a U-shaped association between vitamin B12 and MMSE (P = 0.020) within a certain range. Conclusions: Dietary intake rich in cholesterol and vitamin B12 was associated with better cognitive function, and vitamin B12 had a U-shaped dose-response relation with MMSE. Thus, ensuring moderate cholesterol and vitamin B12 intake may be an advisable strategy to improve cognitive function in middle-aged and older adults.