Impact of vitamin A on aged people’s cognition and Alzheimer’s disease progression in an animal model

The relation between vitamin A (VA) level and cognitive function and the underlying mechanisms have not been thoroughly investigated. Population-based cross-sectional and animal diet intervention studies were conducted to analyze the association between VA nutritional status and cognitive function and the underlying mechanisms. In the population-based study, information from 1817 adults aged 50 years and above was used for data analysis, and we found that subjects with plasma VA level greater than 0.539 μg/ml displayed a lower risk of mild cognitive impairment (MCI). In the animal experiment, VA metabolism was disrupted in Alzheimer's disease (AD) model mice, indicated by increased hepatic VA level and reduced retinol binding protein 4 (RBP4) level. AD model mice fed with low-VA diet showed worse nesting behavior, and cerebral pathologies, including increased Aβ generation, exacerbated neuroinflammation, and impaired brain glucose uptake and insulin signaling pathway. In conclusion, higher plasma VA level (≥ 0.539 μg/ml) might decrease the risk of MCI in the middle-aged and elderly individuals. Low VA nutritional status might disrupt brain glucose metabolism through regulating the insulin signaling pathway, promoting the senile plaque deposit and aggregating cerebral neuroinflammation, finally exacerbating the pathology of AD.