Abstract
Preclinical biological studies in vitro and in vivo as well as epidemiological surveys in humans strongly support the importance of adequate estrogen support for cognitive function in the older female and identify the cognitive and biological consequences of estrogen loss. Nonetheless, therapeutic intervention studies have not shown definitively that estrogen administration is salutary for brain function after menopause, and in fact some studies (e.g., the Women‘s Health Initiative) have actually shown either no improvement or increased risk of cognitive impairment or dementia. Significant progress has been made in understanding the molecular and cellular consequences of estrogen loss and treatment. What has been lacking has been a linkage between these advances in estrogen neurobiology and known mechanisms of age- and disease-related cognitive impairment in humans. This paper briefly reviews advances in the known effects of estrogen on the aging brain and recent evidence regarding the nature of some of the effects of estrogen on human cognitive performance. We then propose that estrogen interactions with brain cholinergic systems may underlie the positive effects of estrogen in aging and link this to clinical syndromes associated with age and neurodegenerative disease.
Acknowledgements
This work was supported by F32 AG 023430 to JD, R01 AG021476 to PN, and NCRR-00109.