AUTHOR=Song Ying , Du Yage , An Yu , Zheng Jie , Lu Yanhui TITLE=A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-ribose JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 14 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.1036315 DOI=10.3389/fnagi.2022.1036315 ISSN=1663-4365 ABSTRACT=Background: D-ribose is an aldehyde sugar that is a necessary component of all living cells. Numerous studies have focused on the animal studies of D-ribose intervention to explore negative effects of D-ribose on cognition. There are inconsistent results between different studies and the actual effects of D-ribose and its dose on cognition remain unclear. This systematic review aimed to define the effect of D-ribose to cognition in rodents. Methods: Articles were screened from PubMed, EMBASE, Sciverse Scopus, Web of science, the Chinese National Knowledge Infrastructure, Sinomed, WanFang, and Cqvip Database. We abstracted the results of the cognitive-related behavioral test and biochemical marker from the included articles and assessed the reporting quality. Results: Eight trials involving 289 rodents met the eligibility criteria, and there wre both low dose and high dose groups. Meta analyses of these studies showed that D-ribose could cause significantly decreased number of platform crossing (SMD: -0.80; 95%CI: -1.14,-0.46; p<0.00001) , percentage of distance in target quadrant (SMD: -1.20; 95%CI: −1.47, −0.92; p<0.00001) , percentage of time in target quadrant (SMD: −0.93; 95%CI: −1.18, −0.68; p<0.00001) , and prolonged escape latency (SMD: 0.41; 95%CI: 0.16, 0.65; p = 0.001) in the Morris water maze test. Besides, D-ribose intervention increased levels of AGEs in the brain (SMD: 0.49; 95%CI:0.34,0.63; p<0.00001) and blood (SMD: 0.50; 95%CI:0.08,0.92; p=0.02). Subsequently, subgroup analysis for dose of D-ribose revealed that D-ribose intervention with high dose injured cognitive function significantly more than in the the group of low D-ribose dose. Conclusion: Our results showed that D-ribose treatment causes cognitive impairment, and the cognition deteriorated with increasing dose. Furthermore, the increase of AGEs in the blood and brain confirms that D-ribose may be involved in cognitive impairment through glycosylation to generate AGEs. These provides a new research idea for unveiling basic mechanism and prospective therapeutic target for the prevention and treatment of patients with cognitive impairment.