Estrogen replacement therapy in older women: A neuropsychological and brain MRI study

OBJECTIVE: To determine if postmenopausal women receiving estrogen perform better on demanding cognitive tests than women without estrogen replacement and if this beneficial effect on cognition is caused by estrogen-related prevention of silent ischemic brain damage. DESIGN: Cross-sectional study comparing postmenopausal estrogen users and non-users. SETTING: Austrian Stroke Prevention Study PARTICIPANTS: A total of 70 women currently using estrogen and 140 women who have never used estrogen from a subset of 222 postmenopausal women without neuropsychiatric or general disease undergoing extensive diagnostic work-up in a large-scale stroke prevention study among randomly selected community members. MEASUREMENTS: Neuropsychological test scores and focal brain abnormalities as well as size of ventricles and cortical sulci as assessed by 1.5 Tesla MRI. RESULTS: Estrogen users performed better than non-users on almost all neuropsychological tests administered. When ANCOVA was used to correct for slight differences between groups in age, length of education, mean arterial blood pressure and self-reported activation, values of P < .05 were noted on tasks assessing conceptualization, attention, and visuopractical skills. After adjustment for multiple comparisons, the differences in conceptualization and visuopractical skills remained significant. MRI showed a lower rate and extent of white matter hyperintensities and a significantly smaller total white matter hyperintensity area in women treated with estrogen (P = .043). The total white matter hyperintensity area was inversely related to the duration of estrogen replacement therapy(P = .040). However, there was no difference in neuropsychological performance between estrogen users with and without white matter abnormalities, and this was also supported by the lack of an association between cognitive test results and the extent of white matter disease. CONCLUSIONS: Our study demonstrated an association between estrogen replacement therapy and better cognitive functioning and a lower rate of clinically unsuspected ischemic brain damage in postmenopausal women.