OBJECTIVE: The great majority of dementia patients (about 60-70%) suffer from Alzheimer disease (AD). The distinctive pathological signs of AD are senile plaques (SPs), neurofibrillary tangles (NFTS), synaptic loss and neurodegeneration. In this study; it is aimed to determine the damage caused by Acetylcholine Mustard Aziridin Ion (AF64A), which induces neurological anomalies, and the therapeutic effect of antioxidant piperine and betaine.MATERIAL AND METHODS: In this study; 24 Sprague-Dawley male rats were used and 4 groups were formed: Group 1 consisting of healthy rats (control, n = 6); Group 2 (n = 6) with experimental dementia induced by AF64A, group 3 (AF64A betaine, n = 6) treated with betaine and 4 (AF64A piperine, n = 6) treated with piperine. The mRNA levels of mitogen activated protein kinase-1 (MAPK-1) in hippocampus tissue, Malondialdehyde (MDA) levels in liver and blood serum samples and reduced glutathione (GSH) levels in liver and erythrocyte samples were investigated. In addition, behavioral differences were determined in terms of duration using the morris water maze test.RESULTS: The highest GSH levels in liver and erythrocytes were determined in piperine-treated group 4 (p <0.01). The highest results were recorded in group 2 and the lowest results were recorded in group 4 (p <0.05) in terms of liver and plasma MDA levels. The best results in brain tissue pathology findings were also observed in the piperine applied group (p <0.05). There was a significant increase in hippocampus MAPK-1 mRNA levels in group 2 whereas a decrease in group 4.CONCLUSIONS:Determined pathological, biochemical and genetic analyzes beside the longest reaction time in the behavior test result showed that the use of AF64A significantly destroys the brain nerve cell. But especially piperine treatment create almost reversible effect onto AF64A damaging act via bring down all negative signs into control level compare to the betaine effect. AF64A application causes a significant level of brain damage in rats, creating a similar effect to Alzheimer's. As an alternative treatment, it shows that the application of betaine and piperine reduces all the negative consequences of AF64A, especially the application of piperine, to almost completely normal levels. These findings indicate that the use of antioxidant piperine may be beneficial in reducing and/or regressing oxidant effects in dementia and especially in AD.