Effects of Hormone Therapy on Patterns of Brain Activation during Cognitive Activity: A Review of Neuroimaging Studies

Abstract

Epidemiological studies suggest that hormone therapy might lower the incidence of Alzheimer’s disease and delay its onset (Tang et al. 1996; Kawas et al. 1997). Behavioral studies suggest that hormone therapy might also protect against age-related declines in memory and other cognitive abilities in individuals who are free of dementia (Resnick et al. 1997; Kampen and Sherwin 1994; Robinson et al. 1994), in part by enhancing encoding while learning new information (Maki et al. 2001). Biological support for these findings comes from animal studies showing beneficial effects of estrogen on neuronal survival and connectivity in regions of the brain subserving memory, in particular, the hippocampus (McEwen et al. 1997). Evidence that estrogen influences brain function in humans comes from neuroimaging studies. In this chapter, we review studies of the effects of hormone therapy on cerebral blood flow, cerebral glucose metabolism, and patterns of brain activity during performance of cognitive tasks. A greater understanding of the effects of hormone therapy on brain function is valuable, because neurophysiological studies offer unique insights into the biological plausibility of the epidemiological and behavioral findings. Studies of the effects of hormone therapy on resting cerebral blood flow and metabolism preceded neuroimaging studies using cognitive challenge paradigms. In the mid-1980s, Namba and Sokoloff (1984) demonstrated that acute administration of high doses of estrogen resulted in significant increases in glucose metabolism in ovariectomized rats. Subsequent studies of cerebral blood flow during the resting state in middle-aged postmenopausal women demonstrated estrogen-related increases at the level of the convexity corresponding to the cerebral vasculature (Greene 2000), in cerebellar and whole brain blood flow (Ohkura et al. 1995), and more specifically across 12