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Tom den Heijer, MSc; Mirjam I. Geerlings, PhD; Albert Hofman, MD, PhD; Frank H. de Jong, PhD; Lenore J. Launer, PhD; Huibert A. P. Pols, MD, PhD; Monique M. B. Breteler, MD, PhD

Arch Neurol. 2003;60:213-220.

Background  Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease.

Objective  To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance.

Design and Setting  Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia.

Participants  Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol.

Main Outcome Measure  Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall).

Results  Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, –0.57 to –0.00) and –0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance.

Conclusion  Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance.

From the Departments of Epidemiology and Biostatistics (Drs den Heijer, Geerlings, Hofman, Pols, and Breteler) and Internal Medicine (Drs de Jong and Pols), Erasmus MC, Rotterdam, and the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht (Dr Geerlings), the Netherlands; and the National Institute on Aging, National Institutes of Health, Bethesda, Md (Dr Launer).

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