Preserved white matter integrity is a marker of familial longevity

Authors

  • Irmhild Altmann-Schneider MD,

    Corresponding author
    1. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
    2. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
    3. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
    • Address correspondence to Dr Altmann-Schneider, Department of Radiology, C2-S, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail: i.altmann-schneider@lumc.nl

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  • Anton J. M. de Craen PhD,

    1. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
    2. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
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  • Ilya M. Veer MSc,

    1. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
    2. Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, the Netherlands
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  • Annette A. van den Berg-Huysmans MSc,

    1. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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  • P. Eline Slagboom PhD,

    1. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
    2. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
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  • Rudi G. J. Westendorp MD, PhD,

    1. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
    2. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
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  • Mark A. van Buchem MD, PhD,

    1. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
    2. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
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  • Jeroen van der Grond PhD,

    1. Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
    2. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, Leiden, the Netherlands
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  • and for the Leiden Longevity Study Group


Abstract

Objective

Brain tissue integrity is highly heritable, and its decline is a common phenomenon of ageing. This study aimed to determine whether the phenotype of familial longevity is marked by a relative preservation of brain tissue microstructure.

Methods

Participants were enrolled in the Leiden Longevity Study. In total, 185 middle-aged to elderly offspring of nonagenarian siblings, who were enriched for familial factors of longevity, were contrasted with 171 environment- and age-matched controls. All subjects underwent 3T whole brain magnetic resonance diffusion tensor imaging.

Results

Voxel-wise analysis revealed widespread age-related decrease of white matter fractional anisotropy and increases of axial, radial, and mean diffusivity (all p < 0.003). Offspring showed higher mean white matter fractional anisotropy (mean [standard error]: offspring, 0.3232 [0.0009]; controls, 0.3212 [0.0009]; p = 0.04) compared to control subjects independent of cardiovascular risk factors. When differences in white matter diffusion parameters between offspring and control subjects were assessed voxel-wise, offspring showed higher white matter fractional anisotropy and lower white matter radial diffusivity predominantly in the callosal genu and body (both p < 0.003). With the effect of chronological age on white matter microstructure taken into account, offspring can be considered 4.5 years “biologically younger” compared to control subjects with regard to white matter integrity.

Interpretation

Both middle-aged to elderly offspring of nonagenarian siblings and control subjects show common age-related decline of white matter integrity, but it is less marked in the callosal genu and body in the offspring. This corresponds to a biological age benefit of 4.5 years of the offspring as compared to the control subjects. Ann Neurol 2013;74:883–892

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