Simultaneous Elevation Of Antioxidant And Endocannabinoid Defense System May Prevent Dementia And Improve Cognitive Function In Humans

Abstract

The incidence of dementia with or without Alzheimer’s disease (AD) is increasing despite extensive mechanistic studies and holistic approaches. There are no effective strategies for prevention or treatment with drugs. Analysis of cellular and molecular investigations suggest that increased oxidative stress is the earliest damage that initiates subsequent cellular defects such as chronic inflammation, mitochondrial dysfunction, increased production of Ab1-42 by cleavage of amyloid precursor protein (APP), hyperphosphorylation of tau protein, proteasome inhibition, and shortening of telomere, which are involved in increasing the risk of dementia. Humans have developed an antioxidant defense system (ADS) and endocannabinoid defense system (ECDS) to protect against external and internal stressors. Increased oxidative stress and chronic inflammation damage both defense systems. Therefore, the simultaneous elevation of these two defense systems may reduce the risk of dementia, improve cognitive function, and the effectiveness of drug therapy. Treatment with individual antioxidant compounds or elevation of endocannabinoids alone has failed to achieve the above goals. This review has proposed that a comprehensive mixture of micronutrients together with a stimulator of ECDS may simultaneously enhance the levels of ADS and ECDS, which can lead to a decrease in the risk of dementia, enhanced cognitive function, and improved efficacy of drug therapy in humans. Such an approach would simultaneously reduce the levels of oxidative damage and markers of chronic inflammation. Pre-clinical and clinical studies should be initiated to test the effectiveness of the proposed hypothesis.