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

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) alpha 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 ER alpha, 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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  • Authors+Show Affiliations

    ,

    Department of Epidemiology & Biostatistics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.

    , , , , , , ,

    Source

    Molecular psychiatry 9:12 2004 Dec pg 1129-35

    MeSH

    Aged
    Alzheimer Disease
    Amygdala
    Apolipoproteins E
    Dementia
    Estrogen Receptor alpha
    European Continental Ancestry Group
    Female
    Genetic Predisposition to Disease
    Hippocampus
    Humans
    Magnetic Resonance Imaging
    Male
    Middle Aged
    Organ Size
    Polymorphism, Genetic
    Prospective Studies
    Risk Factors
    Sex Factors

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15263903

    Citation

    den Heijer, T, et al. "Variations in Estrogen Receptor Alpha Gene and Risk of Dementia, and Brain Volumes On MRI." Molecular Psychiatry, vol. 9, no. 12, 2004, pp. 1129-35.
    den Heijer T, Schuit SC, Pols HA, et al. Variations in estrogen receptor alpha gene and risk of dementia, and brain volumes on MRI. Mol Psychiatry. 2004;9(12):1129-35.
    den Heijer, T., Schuit, S. C., Pols, H. A., van Meurs, J. B., Hofman, A., Koudstaal, P. J., ... Breteler, M. M. (2004). Variations in estrogen receptor alpha gene and risk of dementia, and brain volumes on MRI. Molecular Psychiatry, 9(12), pp. 1129-35.
    den Heijer T, et al. Variations in Estrogen Receptor Alpha Gene and Risk of Dementia, and Brain Volumes On MRI. Mol Psychiatry. 2004;9(12):1129-35. PubMed PMID: 15263903.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Variations in estrogen receptor alpha gene and risk of dementia, and brain volumes on MRI. AU - den Heijer,T, AU - Schuit,S C E, AU - Pols,H A P, AU - van Meurs,J B J, AU - Hofman,A, AU - Koudstaal,P J, AU - van Duijn,C M, AU - Uitterlinden,A G, AU - Breteler,M M B, PY - 2004/7/21/pubmed PY - 2005/3/18/medline PY - 2004/7/21/entrez SP - 1129 EP - 35 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 9 IS - 12 N2 - 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) alpha 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 ER alpha, 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. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/15263903/Variations_in_estrogen_receptor_alpha_gene_and_risk_of_dementia_and_brain_volumes_on_MRI_ L2 - http://dx.doi.org/10.1038/sj.mp.4001553 DB - PRIME DP - Unbound Medicine ER -