Amphetamine exposure and dementia - A hypothesis of the long term sequelae of cognitive enhancers based on opponent process theory.

Abstract

Dementia is a cluster of brain dysfunctions with a characteristic of progressively debilitating in individuals' ability of operating cognitive functions and that affects seriously to patients' daily life. We presented a hypothesis in this article that earlier exposure of a common used cognitive enhancer amphetamine may lead to individuals to be more liable to develop dementia in their later life based on the opponent process theory. The theory proposes that following a positive response, homeostatic changes in brain circuits may function to go opposite to the positive response, thus a cognitive deterioration may incur in later life in the individuals who exposed to amphetamine earlier. Along with the hypothesis, amphetamine is also highly associated with the working hypothesis updated for dementia in terms of beta-amyloid cascade, tau protein, oxidative stress and neural inflammation. Finally, we presented two practical methods to evaluate the hypothesis. In non-human approach, rat model of amphetamine dependence would be employed together with evaluations of behavioral performance of memory test and neurochemical markers associated with oxidative stress. In human approach, a matched-cohort design observational study would be highly recommended.