Methylation/demethylation of DNA, RNA and histone plays important roles in epigenetic functions. Formaldehyde is a significant factor participating in reversible and dynamic methylation of the biomacromolecules. As recently reported, memory formation and cognitive dysfunction are correlated with endogenous formaldehyde metabolism. Imbalance of formaldehyde metabolism affects DNA/RNA methylation and demethylation. Concentrations of endogenous formaldehyde are positively correlated with the severity of cognitive impairment of Alzheimer's patients in clinics. As an epidemiological survey shows, the levels of endogenous formaldehyde in elderly humans are negatively correlated with education years, suggesting that formaldehyde acts like a key factor in human learning and memory. "Live and learn" may mitigate the progression of age-related cognitive impairment resulted from imbalance of formaldehyde metabolism. Further investigation of endogenous formaldehyde involved in epigenetic modificaion and regulation should be carried out to understand the pathomechanism of cognition and cognitive impairment.