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MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers.

Abstract

Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.

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  • Authors+Show Affiliations

    ,

    Department of Veterans Affairs Medical Center, San Francisco, CA, USA. norbert.schuff@ucsf.edu

    , , , , , , , ,

    Source

    Brain : a journal of neurology 132:Pt 4 2009 Apr pg 1067-77

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoproteins E
    Biomarkers
    Cognition Disorders
    Disease Progression
    Female
    Genetic Predisposition to Disease
    Genotype
    Hippocampus
    Humans
    Magnetic Resonance Imaging
    Male
    Peptide Fragments
    Polymorphism, Genetic
    Psychiatric Status Rating Scales
    Sample Size

    Pub Type(s)

    Journal Article
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19251758

    Citation

    Schuff, N, et al. "MRI of Hippocampal Volume Loss in Early Alzheimer's Disease in Relation to ApoE Genotype and Biomarkers." Brain : a Journal of Neurology, vol. 132, no. Pt 4, 2009, pp. 1067-77.
    Schuff N, Woerner N, Boreta L, et al. MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers. Brain. 2009;132(Pt 4):1067-77.
    Schuff, N., Woerner, N., Boreta, L., Kornfield, T., Shaw, L. M., Trojanowski, J. Q., ... Weiner, M. W. (2009). MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers. Brain : a Journal of Neurology, 132(Pt 4), pp. 1067-77. doi:10.1093/brain/awp007.
    Schuff N, et al. MRI of Hippocampal Volume Loss in Early Alzheimer's Disease in Relation to ApoE Genotype and Biomarkers. Brain. 2009;132(Pt 4):1067-77. PubMed PMID: 19251758.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers. AU - Schuff,N, AU - Woerner,N, AU - Boreta,L, AU - Kornfield,T, AU - Shaw,L M, AU - Trojanowski,J Q, AU - Thompson,P M, AU - Jack,C R,Jr AU - Weiner,M W, AU - ,, Y1 - 2009/02/27/ PY - 2009/3/3/entrez PY - 2009/3/3/pubmed PY - 2009/10/2/medline SP - 1067 EP - 77 JF - Brain : a journal of neurology JO - Brain VL - 132 IS - Pt 4 N2 - Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/19251758/MRI_of_hippocampal_volume_loss_in_early_Alzheimer's_disease_in_relation_to_ApoE_genotype_and_biomarkers_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awp007 DB - PRIME DP - Unbound Medicine ER -