Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Being overweight is associated with hippocampal atrophy: the PATH Through Life Study

International Journal of Obesity volume 39, pages 1509–1514 (2015)Cite this article

Subjects

Abstract

Background:

The prevalence of obesity has increased dramatically in the past two decades, with major implications for individual well-being, population health and the economy. Of particular concern is the risk obesity presents for brain health and its consequences in an ageing population. These associations and their time course are not well understood, particularly after middle age. The aim of this study was to investigate whether being overweight/obese or having an increasing body weight is associated with hippocampal atrophy in early old age.

Methods:

Participants were 420 unimpaired (Mini-Mental State Examination >26) individuals aged 60–64 years, living in the community and taking part in a large prospective study of ageing over an 8 year follow-up. Magnetic resonance imaging scans were collected at three assessments and the hippocampus was manually traced by expert neuroscientists. Multi-level analyses assessing the relationship between body mass index (BMI) and hippocampal atrophy over 8 years while controlling for important covariates were conducted.

Results:

Analyses showed that BMI was negatively associated with left (coefficient: −10.65 mm3; s.e. 4.81; P=0.027) and right (coefficient: −8.18 mm3; s.e. 4.91; P=0.097) hippocampal volume at the first assessment. Over the follow-up period, those with a higher BMI experienced greater hippocampal atrophy and more so in the left (P=0.001) than in the right (P=0.058) hippocampus.

Conclusions:

The findings from this study provide important evidence indicating that being overweight or obese is associated with poorer brain health. These results are consistent with those of previous animal and human studies and further stress the importance of reducing the rate of obesity through education, population health interventions and policy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Ogden CL, Carroll MD, Kit BK, Flegal KM . Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014; 311: 806–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Australian Bureau of Statistics Australian Health Survey: First Results, 2011–2012. Commonwealth of Australia: Canberra, Australia, 2012.

  3. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011; 377: 557–567.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Anstey KJ, Cherbuin N, Budge M, Young J . Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev 2011; 12: e426–e437.

    Article  CAS  PubMed  Google Scholar 

  5. Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK et al. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol 2010; 219: 25–32.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang X, Dong F, Ren J, Driscoll MJ, Culver B . High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Exp Neurol 2005; 191: 318–325.

    Article  CAS  PubMed  Google Scholar 

  7. Cai D . Neuroinflammation and neurodegeneration in overnutrition-induced diseases. Trends Endocrinol Metab 2013; 24: 40–47.

    Article  CAS  PubMed  Google Scholar 

  8. Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ et al. Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 2012; 61: 1444–1454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Miller AA, Spencer SJ . Obesity and neuroinflammation: A pathway to cognitive impairment. Brain Behav Immun 2014; 42: 10–21.

    Article  CAS  PubMed  Google Scholar 

  10. Julien C, Tremblay C, Phivilay A, Berthiaume L, Emond V, Julien P et al. High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model. Neurobiol Aging 2010; 31: 1516–1531.

    Article  CAS  PubMed  Google Scholar 

  11. Lee EB . Obesity, leptin, and Alzheimer's disease. Ann NY Acad Sci 2011; 1243: 15–29.

    Article  CAS  PubMed  Google Scholar 

  12. Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH et al. Brain structure and obesity. Hum Brain Mapp 2010; 31: 353–364.

    PubMed  Google Scholar 

  13. Bailey-Downs LC, Tucsek Z, Toth P, Sosnowska D, Gautam T, Sonntag WE et al. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation. J Gerontol A Biol Sci Med Sci 2013; 68: 780–792.

    Article  CAS  PubMed  Google Scholar 

  14. Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging 2010; 31: 1326–1339.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Anstey KJ, Christensen H, Butterworth P, Easteal S, Mackinnon A, Jacomb T et al. Cohort profile: the PATH through life project. Int J Epidemiol 2012; 41: 951–960.

    Article  PubMed  Google Scholar 

  16. Goldberg D, Bridges K, Duncan-Jones P, Grayson D . Detecting anxiety and depression in general medical settings. BMJ 1988; 297: 897–899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jette M, Sidney K, Blumchen G . Metabolic equivalents (METS) in exercise testing, exercise prescription, and evaluation of functional capacity. Clin Cardiol 1990; 13: 555–565.

    Article  CAS  PubMed  Google Scholar 

  18. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000; 32: S498–S504.

    Article  CAS  PubMed  Google Scholar 

  19. Watson C, Jack CR, Cendes F . Volumetric magnetic resonance imaging. Clinical applications and contributions to the understanding of temproal lobe epilepsy. Arch Neurol 1997; 9: 97–113.

    Google Scholar 

  20. Maller JJ, Anstey KJ, Reglade-Meslin C, Christensen H, Wen W, Sachdev P . Hippocampus and amygdala volumes in a random community-based sample of 60-64 year olds and their relationship to cognition. Psychiatry Res 2007; 156: 185–197.

    Article  PubMed  Google Scholar 

  21. Cherbuin N, Sachdev PS, Anstey KJ . Mixed handedness is associated with greater age-related decline in volumes of the hippocampus and amygdala: the PATH through life study. Brain Behav 2011; 1: 125–134.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Xu Z, Shen X, Pan W . Longitudinal analysis is more powerful than cross-sectional analysis in detecting genetic association with neuroimaging phenotypes. PLoS One 2014; 9: e102312.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lehr S, Hartwig S, Lamers D, Famulla S, Muller S, Hanisch F G et al. Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics 2012; 11: M111.010504.

    Article  PubMed  Google Scholar 

  24. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997; 82: 4196–4200.

    CAS  PubMed  Google Scholar 

  25. Aguilar-Valles A, Inoue W, Rummel C, Luheshi GN . Obesity, adipokines and neuroinflammation. Neuropharmacology 2015; 96: 124–134.

    Article  CAS  PubMed  Google Scholar 

  26. Erion JR, Wosiski-Kuhn M, Dey A, Hao S, Davis CL, Pollock NK et al. Obesity elicits interleukin 1-mediated deficits in hippocampal synaptic plasticity. J Neurosci 2014; 34: 2618–2631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dugan LL, Ali SS, Shekhtman G, Roberts AJ, Lucero J, Quick KL et al. IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH oxidase. PLoS One 2009; 4: e5518.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sudheimer KD, O'Hara R, Spiegel D, Powers B, Kraemer HC, Neri E et al. Cortisol, cytokines, and hippocampal volume interactions in the elderly. Front Aging Neurosci 2014; 6: 153.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ng SP, Korda R, Clements M, Latz I, Bauman A, Bambrick H et al. Validity of self-reported height and weight and derived body mass index in middle-aged and elderly individuals in Australia. Aust N Z J Public Health 2011; 35: 557–563.

    Article  PubMed  Google Scholar 

  30. Lee EB, Mattson MP . The neuropathology of obesity: insights from human disease. Acta Neuropathol 2014; 127: 3–28.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Anthony Jorm, Helen Christensen, Peter Butterworth, Chantal Réglade-Meslin, Jerome Maller, Patricia Jacomb, Karen Maxwell and the PATH project interviewers. The study was supported by NHMRC Grant 973302, 179805, 157125 and 1063907 and ARC Grant 130101705. Nicolas Cherbuin and Kaarin Anstey’s Research Fellowship are funded by ARC 120100227 and NHMRC 1002560. This research was partly undertaken on the National Computational Infrastructure (NCI) facility in Canberra, Australia, which is supported by the Australian Commonwealth Government.

Author Contributions

Associate Professor Cherbuin contributed to the design of the study, conducted all statistical analyses and managed all aspects of manuscript preparation and submission. Dr Sargent-Cox provided methodological input and assisted with the statistical analyses and contributed to the editing of the manuscript. Mr Mark Fraser assisted with the analyses and the compilation of results and contributed to the editing of the manuscript. Professor Sachdev contributed to the design of the study, provided methodological input and theoretical expertise and contributed to writing and editing of the manuscript. Professor Anstey contributed to the design of the study, provided methodological input and theoretical expertise and contributed to writing and editing of the manuscript.

Author information

Authors and Affiliations

  1. Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australian Capital Territory, Australia

    N Cherbuin, K Sargent-Cox, M Fraser & K J Anstey

  2. School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia

    P Sachdev

Authors
  1. N Cherbuin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Sargent-Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Sachdev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K J Anstey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Cherbuin.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cherbuin, N., Sargent-Cox, K., Fraser, M. et al. Being overweight is associated with hippocampal atrophy: the PATH Through Life Study. Int J Obes 39, 1509–1514 (2015). https://doi.org/10.1038/ijo.2015.106

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2015.106

This article is cited by

Search

Advanced search

Quick links