Can dietary supplements prevent cognitive decline observed in aging and Alzheimer's disease

Folate deficiency has been indicated in many neurological and psychological disorders, among them, dementia, cognitive impairment, and AD. Folate deficiency increases neuronal oxidative stress, in part by increasing levels of the neurotoxin homocysteine (HC), which is related to the progression and severity of AD. Moreover, a direct consequence of folate deficiency is a decline in the major methyl donor, S-adenosyl methionine (SAM). It has been shown, in conjunction with other laboratories, that the overexpression of presenilin-1 (PS-1), the resultant overactivation of gamma secretase, and the subsequent increase in Abeta production, are downstream consequences of folate deprivation due to diminished levels of SAM. Additionally, it has been demonstrated herein that pro-oxidant stress and dietary folate deficiency decreased levels of acetylcholine, and impaired cognitive performance to various degrees in normal adult mice, transgenic models of AD, and aged normal mice. Dietary supplementation with SAM in the absence of folate quenched PS-1 expression, and thus prevented the subsequent gamma secretase-mediated cascade. In addition to reducing Abeta production, SAM supplementation was able to prevent tau hyperphosphorylation, an event normally increased under conditions of folate deficiency. Furthermore, acetylcholine levels and cognitive performance were restored to respective levels observed in the presence of folate. Increased aggressive behavior was observed among some, but not all genotypes when maintained on a vitamin-deficient diet, and was eliminated in all cases when supplementated with SAM. Of further note is the research which has demonstrated that apple juice supplementation results in many of the same outcomes as does the dietary addition of SAM. The opportunity to translate these studies into clinical trials has lent support to the significance of adequate folate for maintenance of the nervous system, as well as highlighted dietary supplementation with SAM and apple juice as important therapeutic approaches for age-related neurodegeneration.