Skip to main content
SpringerLink
Log in

Statistical estimation of physiological brain age as a descriptor of senescence rate during adulthood

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Mapping aging-related brain structure and connectivity changes can be helpful for assessing physiological brain age (PBA), which is distinct from chronological age (CA) because genetic and environmental factors affect individuals differently. This study proposes an approach whereby structural and connectomic information can be combined to estimate PBA as an early biomarker of brain aging. In a cohort of 136 healthy adults, magnetic resonance and diffusion tensor imaging are respectively used to measure cortical thickness over the entire cortical mantle as well as connectivity properties (mean connectivity density and mean fractional anisotropy) for white matter connections. Using multivariate regression, these measurements are then employed to (1) illustrate how CA can be predicated—and thereby also how PBA can be estimated—and to conclude that (2) healthy aging is associated with significant connectome changes during adulthood. Our study illustrates a connectomically-informed statistical approach to PBA estimation, with potential applicability to the clinical identification of patients who exhibit accelerated brain aging, and who are consequently at higher risk for developing mild cognitive impairment or dementia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate - a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B - Methodological, 57(1), 289–300.

    Google Scholar 

  • Cheng, Y., Chou, K. H., Chen, I. Y., Fan, Y. T., Decety, J., & Lin, C. P. (2010). Atypical development of white matter microstructure in adolescents with autism spectrum disorders. NeuroImage, 50(3), 873–882.

    Article  CAS  PubMed  Google Scholar 

  • Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis—I. Segmentation and surface reconstruction. NeuroImage, 9(2), 179–194.

    Article  CAS  PubMed  Google Scholar 

  • de Jong, B. M., van der Graaf, F. H., & Paans, A. M. (2001). Brain activation related to the representations of external space and body scheme in visuomotor control. NeuroImage, 14(5), 1128–1135.

    Article  PubMed  Google Scholar 

  • Dennis, E. L., & Thompson, P. M. (2013). Mapping connectivity in the developing brain. International Journal of Developmental Neuroscience, 31(7), 525–542.

    Article  CAS  PubMed  Google Scholar 

  • Dickerson, B. C., Wolk, D. A., & Initi, A. D. N. (2012). MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults. Neurology, 78(2), 84–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dickie, D. A., Job, D. E., Gonzalez, D. R., Shenkin, S. D., Ahearn, T. S., Murray, A. D., et al. (2013). Variance in brain volume with advancing age: implications for defining the limits of normality. PLos One, 8(12), e84093.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ernst, T., Speck, O., Itti, L., & Chang, L. (1999). Simultaneous correction for interscan patient motion and geometric distortions in echoplanar imaging. Magnetic Resonance in Medicine, 42(1), 201–205.

    Article  CAS  PubMed  Google Scholar 

  • Filimon, F., Nelson, J. D., Huang, R. S., & Sereno, M. I. (2009). Multiple parietal reach regions in humans: cortical representations for visual and proprioceptive feedback during on-line reaching. Journal of Neuroscience, 29(9), 2961–2971.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis—II: inflation, flattening, and a surface-based coordinate system. NeuroImage, 9(2), 195–207.

    Article  CAS  PubMed  Google Scholar 

  • Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., et al. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355.

    Article  CAS  PubMed  Google Scholar 

  • Fjell, A. M., Walhovd, K. B., Fennema-Notestine, C., McEvoy, L. K., Hagler, D. J., Holland, D., et al. (2009a). One-year brain atrophy evident in healthy aging. Journal of Neuroscience, 29(48), 15223–15231.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fjell, A. M., Westlye, L. T., Amlien, I., Espeseth, T., Reinvang, I., Raz, N., et al. (2009b). High consistency of regional cortical thinning in aging across multiple samples. Cerebral Cortex, 19(9), 2001–2012.

    Article  PubMed Central  PubMed  Google Scholar 

  • Freire, L., & Mangin, J. F. (2001). Motion correction algorithms may create spurious brain activations in the absence of subject motion. NeuroImage, 14(3), 709–722.

    Article  CAS  PubMed  Google Scholar 

  • Frisoni, G. B., Pievani, M., Testa, C., Sabattoli, F., Bresciani, L., Bonetti, M., et al. (2007). The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain, 130, 720–730.

    Article  PubMed  Google Scholar 

  • Goldberg, S., Smith, G. S., Barnes, A., Ma, Y., Kramer, E., Robeson, K., et al. (2004). Serotonin modulation of cerebral glucose metabolism in normal aging. Neurobiology of Aging, 25(2), 167–174.

    Article  CAS  PubMed  Google Scholar 

  • Gur, R. E., Turetsky, B. I., Bilker, W. B., & Gur, R. C. (1999). Reduced gray matter volume in schizophrenia. Archives of General Psychiatry, 56(10), 905–911.

    Article  CAS  PubMed  Google Scholar 

  • Hagmann, P., Cammoun, L., Gigandet, X., Meuli, R., Honey, C. J., Wedeen, V., et al. (2008). Mapping the structural core of human cerebral cortex. PLos Biology, 6(7), 1479–1493.

    Article  CAS  Google Scholar 

  • Herbst, M., Maclaren, J., Lovell-Smith, C., Sostheim, R., Egger, K., Harloff, A., et al. (2014). Reproduction of motion artifacts for performance analysis of prospective motion correction in MRI. Magnetic Resonance in Medicine, 71(1), 182–190.

    Article  PubMed  Google Scholar 

  • Ingalhalikar, M., Smith, A., Parker, D., Satterthwaite, T. D., Elliott, M. A., Ruparel, K., et al. (2014). Sex differences in the structural connectome of the human brain. Proceedings of the National Academy of Sciences of the United States of America, 111(2), 823–828.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ino, T., Inoue, Y., Kage, M., Hirose, S., Kimura, T., & Fukuyama, H. (2002). Mental navigation in humans is processed in the anterior bank of the parieto-occipital sulcus. Neuroscience Letters, 322(3), 182–186.

    Article  CAS  PubMed  Google Scholar 

  • Lemaitre, H., Goldman, A. L., Sambataro, F., Verchinski, B. A., Meyer-Lindenberg, A., Weinberger, D. R., et al. (2012). Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiology of Aging, 33(3), 617.e611–617.e619.

    Article  Google Scholar 

  • Lerch, J. P., Pruessner, J., Zijdenbos, A. P., Collins, D. L., Teipel, S. J., Hampel, H., et al. (2008). Automated cortical thickness measurements from MRI can accurately separate Alzheimer’s patients from normal elderly controls. Neurobiology of Aging, 29(1), 23–30.

    Article  PubMed  Google Scholar 

  • McDonald, C. R., McEvoy, L. K., Gharapetian, L., Fennema-Notestine, C., Hagler, D. J., Holland, D., et al. (2009). Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology, 73(6), 457–465.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Miller, A. K., Alston, R. L., & Corsellis, J. A. (1980). Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropathology and Applied Neurobiology, 6(2), 119–132.

    Article  CAS  PubMed  Google Scholar 

  • Narr, K. L., Bilder, R. M., Toga, A. W., Woods, R. P., Rex, D. E., Szeszko, P. R., et al. (2005). Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex, 15(6), 708–719.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., & Sullivan, E. V. (2003). Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming. Magnetic Resonance in Medicine, 49(5), 953–961.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Sullivan, E. V., Hedehus, M., Lim, K. O., Adalsteinsson, E., & Moseley, M. (2000). Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magnetic Resonance in Medicine, 44(2), 259–268.

    Article  CAS  PubMed  Google Scholar 

  • Qin, L., Schmidt, E. J., Tse, Z. T. H., Santos, J., Hoge, W. S., Tempany-Afdhal, C., et al. (2013). Prospective motion correction using tracking coils. Magnetic Resonance in Medicine, 69(3), 749–759.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rencher, A. C. (2002). Methods of multivariate analysis. New York: Wiley.

    Book  Google Scholar 

  • Rohde, G. K., Barnett, A. S., Basser, P. J., Marenco, S., & Pierpaoli, C. (2004). Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI. Magnetic Resonance in Medicine, 51(1), 103–114.

    Article  CAS  PubMed  Google Scholar 

  • Salat, D. H., Buckner, R. L., Snyder, A. Z., Greve, D. N., Desikan, R. S., Busa, E., et al. (2004). Thinning of the cerebral cortex in aging. Cerebral Cortex, 14(7), 721–730.

    Article  PubMed  Google Scholar 

  • Sowell, E. R., Peterson, B. S., Thompson, P. M., Welcome, S. E., Henkenius, A. L., & Toga, A. W. (2003). Mapping cortical change across the human life span. Nature Neuroscience, 6(3), 309–315.

    Article  CAS  PubMed  Google Scholar 

  • Sowell, E. R., Thompson, P. M., & Toga, A. W. (2004). Mapping changes in the human cortex throughout the span of life. The Neuroscientist, 10(4), 372–392.

    Article  PubMed  Google Scholar 

  • Sullivan, E. V., & Pfefferbaum, A. (2006). Diffusion tensor imaging and aging. Neuroscience and Biobehavioral Reviews, 30(6), 749–761.

    Article  PubMed  Google Scholar 

  • Thambisetty, M., Wan, J., Carass, A., An, Y., Prince, J. L., & Resnick, S. M. (2010). Longitudinal changes in cortical thickness associated with normal aging. NeuroImage, 52(4), 1215–1223.

    Article  PubMed Central  PubMed  Google Scholar 

  • Thompson, P. M., Hayashi, K. M., de Zubicaray, G., Janke, A. L., Rose, S. E., Semple, J., et al. (2003). Dynamics of gray matter loss in Alzheimer’s disease. Journal of Neuroscience, 23(3), 994–1005.

    CAS  PubMed  Google Scholar 

  • Thompson, P. M., Hayashi, K. M., Simon, S. L., Geaga, J. A., Hong, M. S., Sui, Y. H., et al. (2004). Structural abnormalities in the brains of human subjects who use methamphetamine. Journal of Neuroscience, 24(26), 6028–6036.

    Article  CAS  PubMed  Google Scholar 

  • Ugurbil, K., Xu, J. Q., Auerbach, E. J., Moeller, S., Vu, A. T., Duarte-Carvajalino, J. M., et al. (2013). Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project. NeuroImage, 80, 80–104.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Van Horn, J. D., & Toga, A. W. (2009). Brain atlases: Their development and role in functional inference. In M. Filippi (Ed.), fMRI techniques and protocols (Vol. 41, pp. 263–281). New York: Humana Press.

    Chapter  Google Scholar 

  • Vanni, S., Revonsuo, A., & Hari, R. (1997). Modulation of the parieto-occipital alpha rhythm during object detection. Journal of Neuroscience, 17(18), 7141–7147.

    CAS  PubMed  Google Scholar 

  • Walhovd, K. B., Fjell, A. M., Reinvang, I., Lundervold, A., Dale, A. M., Eilertsen, D. E., et al. (2005). Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiology of Aging, 26(9), 1261–1270.

    Article  PubMed  Google Scholar 

  • Wang, L., Goldstein, F. C., Veledar, E., Levey, A. I., Lah, J. J., Meltzer, C. C., et al. (2009). Alterations in cortical thickness and white matter integrity in mild cognitive impairment measured by whole-brain cortical thickness mapping and diffusion tensor imaging. American Journal of Neuroradiology, 30(5), 893–899.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Webb, N. M., Shavelson, R. J., & Haertel, E. H. (2006). Reliability coefficients and generalizability theory. In C. R. Rao, & S. Sinharay (Eds.), Handbook of Statistics (Vol. 26: Psychometrics, pp. 81–125, Vol. 26). Amsterdam, Netherlands: Elsevier B.V.

  • Wenger, E., Schaefer, S., Noack, H., Kuhn, S., Martensson, J., Heinze, H. J., et al. (2012). Cortical thickness changes following spatial navigation training in adulthood and aging. NeuroImage, 59(4), 3389–3397.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health, grants 2U54EB005149-06 “National Alliance for Medical Image Computing: Traumatic Brain Injury – Driving Biological Project” to J.D.V.H., and R41NS081792-01 “Multimodality Image Based Assessment System for Traumatic Brain Injury”, subaward to J.D.V.H. We wish to thank the dedicated staff of the Institute for Neuroimaging and Informatics at the University of Southern California. Disclosure statement: Andrei Irimia, Carinna M. Torgerson, S.-Y. Matthew Goh, and John D. Van Horn declare no actual or potential competing conflicts of interest.

Author information

Authors and Affiliations

  1. Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, 2001 North Soto Street, Room 102, MC 9232, Los Angeles, CA, 90089-9235, USA

    Andrei Irimia, Carinna M. Torgerson, S.-Y. Matthew Goh & John D. Van Horn

Authors
  1. Andrei Irimia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carinna M. Torgerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S.-Y. Matthew Goh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John D. Van Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John D. Van Horn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Irimia, A., Torgerson, C.M., Goh, SY.M. et al. Statistical estimation of physiological brain age as a descriptor of senescence rate during adulthood. Brain Imaging and Behavior 9, 678–689 (2015). https://doi.org/10.1007/s11682-014-9321-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-014-9321-0

Keywords

Search

Navigation