This review focuses on the relationship between excess endogenous formaldehyde and memory decline, as well as multi-factors inducing formaldehyde abnormal accumulation and cognitive impairments. Elevation of endogenous formaldehyde concentrations in Alzheimer's animal models and clinical patients was discussed. Injection with formaldehyde (referred to the detected level in the AD animal models) into normal mice obviously induced spatial memory decline. Aging, and some of genetic factors, diet and environmental pollutants led to formaldehyde abnormal accumulation. Formaldehyde scavengers could rescue spatial memory of APP-transgenic mice. These studies addressed that excess formaldehyde-induced damage of brain is one of the critical factors of cognitive impairments of sporadic senile dementia. Scavenging excess formaldehyde may be a novel therapy for Alzheimer's disease.