Hormones and cognition

As the number of older people continues to grow, the incidence of Alzheimer’s disease is expected to keep pace. And because women typically outlive men, women are expected to be hardest hit.

Early studies trying to link estrogen use in postmenopausal women to changes in cognitive function or the incidence of Alzheimer’s disease have been ambiguous. In 1998, Kristine Yaffe and her colleagues at the University of California at San Francisco reported that serum concentrations of estrogenic hormones—estradiol and estrone—were not consistently associated with cognitive function or risk of decline in older women. (J. Am. Geriatr. Soc. 1998, 46, 816–821).

Recently, however, Yaffe and her co-workers suggested that total hormonal concentration might not be the best indicator of hormonal activity. Instead, they argue that the non-protein-bound and loosely bound (bioavailable) forms of the hormone cross the blood–brain barrier more readily and may better correlate with cognitive function (Lancet 2000, 356, 708–712).

Evaluating the cognitive performance of 425 women aged 65 or older at the beginning and end of a 6-year study, the researchers found that women with high serum concentrations of bioavailable estradiol were less likely to develop cognitive impairment than women with low concentrations. The investigators believe that higher concentrations of endogenous estrogens may have prevented cognitive decline. In similar analyses of testosterone levels, no link was found with cognitive impairment risk.

Unfortunately, while many postmenopausal women take relatively high doses of supplemental estrogen in the belief that it might diminish the risk of Alzheimer’s disease, the long-term use of estrogen is associated with side effects such as an increased risk of breast cancer and vascular disease.

But Yaffe’s study suggests that low doses of estrogen may offer the same benefits and that women with little bioavailable estradiol may benefit most from estrogen therapy.