Relationship between androgen deficiency and memory impairment in aging and Alzheimer’s disease

Abstract

Aging and Alzheimer’s disease (AD) are associated with a declination of cognition and memory, whose severity increases in AD. Recent investigations point to a greater participation of neurofibrillary tangles (NFTs) than that of senile plaques, as responsible for cognitive impairment in AD and normal aging. On the other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies give evidence that hypoandrogenism is associated with memory impairment. Accordingly, some animal studies show that the administration of these hormones improves the performance of cognitive tasks. However, effects of DHEA, DHEA-S, and T in the clinical setting, are not clear in part because of the balance between the benefits and risks of hormone therapy in aging subjects and because the cellular mechanism underlying its effects on memory in old age and related pathologies are unknown. The objective of this review is to analyze the role of DHEA, DHEA-S, and T, on memory in normal aging and in AD, and to determine whether these hormones modulate the hyperphosphorylation of tau protein, a molecular marker in AD pathology. The method used in the review included articles from the PubMed database, using the following search terms: DHEA, DHEA-S, T, memory, androgen deprivation therapy, tau protein, aging, and AD. Finally, we analyze the use of these steroids as an adjunct in the treatment of memory deficits in aging subjects and AD patients.