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Variations in estrogen receptor α gene and risk of dementia, and brain volumes on MRI

Molecular Psychiatry volume 9, pages 1129–1135 (2004)Cite this article

Abstract

The role of estrogens in Alzheimer's disease (AD) is controversial. We investigated the association between well-recognized, and potentially functional, polymorphisms in the estrogen receptor (ER) α gene and the risk of AD in a prospective study of 6056 Caucasian older men and women aged 55 years and over. In a subset of 468 participants, we assessed volumes of the hippocampus and amygdala, which have a high density of ERα, with brain magnetic resonance imaging (MRI) (1.5 T MR unit). During a total of 35 405 person-years of follow-up (mean per persons 5.8 years), 312 new cases of dementia were detected, of whom 230 were diagnosed with AD. Neither the PvuII nor the XbaI polymorphism or haplotypes thereof were associated with the risk of all-cause dementia or AD. In contrast, we found that nondemented women who carried the PvuII p allele or haplotype ‘px’ had smaller amygdalar volumes on MRI in an allele–dose-dependent fashion. Total amygdalar volume was 4.50 (SE 0.10) in PP genotype, 4.45 (SE 0.06) in Pp genotype, and 4.18 ml (SE 0.08) in pp genotype (P trend=0.008). Further studies are required to investigate whether this smaller amygdalar volume has functional significance.

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Acknowledgements

The Rotterdam Study has been supported by the Research Institute for Diseases in the Elderly, funded by the Ministry of Education & Science and the Ministry of Health, Welfare and Sports, through the Netherlands Organization for Scientific Research (NWO grant 014-90-001). We thank Freek Hoebeek and Eric Achten for their help in measuring the hippocampus and the amygdala and Wendy Hugens for technical assistance in the DNA analysis.

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Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

    T den Heijer, S C E Schuit, H A P Pols, J B J van Meurs, A Hofman, C M van Duijn, A G Uitterlinden & M M B Breteler

  2. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

    T den Heijer & P J Koudstaal

  3. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    S C E Schuit, H A P Pols, J B J van Meurs & A G Uitterlinden

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  1. T den Heijer
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den Heijer, T., Schuit, S., Pols, H. et al. Variations in estrogen receptor α gene and risk of dementia, and brain volumes on MRI. Mol Psychiatry 9, 1129–1135 (2004). https://doi.org/10.1038/sj.mp.4001553

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Keywords

  • Alzheimer's disease
  • hippocampus
  • amygdala
  • steroid hormone receptor

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