Review Article | Published:

Modifiable factors that alter the size of the hippocampus with ageing

Nature Reviews Neurology volume 8, pages 189202 (2012) | Download Citation

Abstract

The hippocampus is particularly vulnerable to the neurotoxic effects of obesity, diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea, bipolar disorder, clinical depression and head trauma. Patients with these conditions often have smaller hippocampi and experience a greater degree of cognitive decline than individuals without these comorbidities. Moreover, hippocampal atrophy is an established indicator for conversion from the normal ageing process to developing mild cognitive impairment and dementia. As such, an important aim is to ascertain which modifiable factors can have a positive effect on the size of the hippocampus throughout life. Observational studies and preliminary clinical trials have raised the possibility that physical exercise, cognitive stimulation and treatment of general medical conditions can reverse age-related atrophy in the hippocampus, or even expand its size. An emerging concept—the dynamic polygon hypothesis—suggests that treatment of modifiable risk factors can increase the volume or prevent atrophy of the hippocampus. According to this hypothesis, a multidisciplinary approach, which involves strategies to both reduce neurotoxicity and increase neurogenesis, is likely to be successful in delaying the onset of cognitive impairment with ageing. Further research on the constellation of interventions that could be most effective is needed before recommendations can be made for implementing preventive and therapeutic strategies.

Key points

  • Atrophy in the hippocampus is a key factor in the process of age-related memory loss and dementia, and might not be solely attributable to Alzheimer disease pathology

  • Automated MRI measurements of brain size assist in detecting reductions or expansions in hippocampal volume, which can occur with ageing, some medical conditions or neurodegeneration

  • Vascular risk factors, such as obesity, diabetes mellitus and obstructive sleep apnoea, are associated with a reduction in hippocampal size and early development of cognitive impairment

  • Elevated levels of inflammatory markers and cortisol, and dynamic changes in the levels of several enzymes and transcription factors, have been implicated in hippocampal atrophy

  • Cognitive stimulation, physical exercise and treatment of vascular risk factors seem to result in measurable increases in hippocampal volume, in addition to improvements in memory

  • Improved understanding of the modifiable factors that cause changes in hippocampal volume throughout life will assist in the development of clinical trials aimed at preventing age-related cognitive impairment

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Acknowledgements

The authors would like to thank Dr M. Haan, Dr T. den Heijer, E. Mayeda, Dr V. Carrion, Dr C. Weems and Dr G. Musen for sharing their data on hippocampal volumetry.

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  1. Neurology Institute for Brain Health and Fitness, 1205 York Road, Suite 18, Lutherville, MD 21093, USA

    • Majid Fotuhi
  2. Johns Hopkins University School of Medicine, 733 North Broadway, Suite 137, Baltimore, MD 21205, USA

    • David Do
  3. Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA

    • Clifford Jack

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All authors contributed to discussions of the article content, writing the article and to review and/or editing of the manuscript before submission. In addition, M. Fotuhi and D. Do researched the data for the article.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Majid Fotuhi.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrneurol.2012.27

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