Predicting memory decline as a risk factor for Alzheimer's disease in older post-menopausal women: quod erat demonstrandum?

Abstract

Alzheimer's disease (AD) is the major form of age-related dementia worldwide, accounting for more than two-thirds of all dementia cases. The disease is characterized by a progressive loss of cognitive and intellectual functioning (Gilman, 1997). A number of risk factors for AD have been identified. The prevalence of AD increases with age, diabetes, depression, family history of Parkinson's disease and following head injury or exposure to solvents (Jorm et al., 1991; van Duijn et al., 1991; Ott et al., 1995; Yoshitake et al., 1995; Devanand et al., 1996). Published research further suggests that low education levels are associated with increased prevalence of clinical AD (Gatz et al., 2001; Qiu et al., 2001; Ravaglia et al., 2002). Women also have a higher risk for developing the disease than men, with the risk being markedly increased following menopause (Sherwin, 2002; Sherwin 2003). Additionally, slightly more severe cognitive deficits have been reported in AD in women compared to men (Buckwalter et al., 1993, Henderson and Buckwalter, 1994). These epidemiological trends may be a consequence of reproductive hormonal changes. Specifically, menopause results in a marked diminution in gonadal estrogen production in women (see Sherwin, 2003, for a review). Estrogen plays a pivotal role in the maintenance and function of neuronal circuits in the brain and in resistance to neuronal damage (McEwen, 2001). The neuroprotective properties of estrogen are thought to be mediated at least in part by anti-amyloidogenic, anti-oxidative and ant-inflammatory mechanisms (reviewed in Barron et al., 2006a). However, limited and somewhat mixed data exist regarding the association between endogenous levels of estrogen and cognitive decline (Manly et al., 2000; Schupf et al., 2003). Based on some of our own findings, we here consider the factors that may be useful in predicting memory decline as a risk factor for Alzheimer's disease in older post-menopausal women.