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The clinical use of structural MRI in Alzheimer disease

Nature Reviews Neurology volume 6, pages 67–77 (2010)Cite this article

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Abstract

Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment.

Key Points

  • Brain atrophy detected by high-resolution MRI is correlated with both tau deposition and neuropsychological deficits, and is a valid marker of Alzheimer disease (AD) and its progression

  • The degree of atrophy of medial temporal structures such as the hippocampus is a diagnostic marker for AD at the mild cognitive impairment stage

  • Structural imaging markers are included in diagnostic criteria for non-AD dementias, such as vascular dementia, frontotemporal degeneration, dementia with Lewy bodies, and Creutzfeldt–Jakob disease, and can aid differential diagnosis

  • Whole-brain and hippocampal atrophy rates are sensitive markers of progression of neurodegeneration, and are increasingly used as surrogate outcomes in trials of potentially disease-modifying drugs

  • In the near future, imaging and cerebrospinal fluid markers of amyloid deposition and glucose metabolism could be integrated with automated assessment of structural markers for optimal diagnosis and monitoring

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Figure 1: Natural progression of cognitive and biological markers of Alzheimer disease: a theoretical model.
Figure 2: Progressive enrichment of a mild cognitive impairment cohort with future converters to Alzheimer dementia by screening for low hippocampal volume.
Figure 3: Effect of severe WMLs on the progression of cognitive deterioration.
Figure 4: Cortical thinning in patients with mild cognitive impairment.

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Acknowledgements

Anna Caroli, Enrica Cavedo, Rossana Ganzola, Marco Lorenzi, Michela Pievani, Annapaola Prestia, Alberto Redolfi and Cristina Scarpazza helped in the literature review, Rossana Ganzola helped in the typesetting of the manuscript, and Alberto Redolfi produced the maps of Figure 4. G. B. Frisoni was supported by FP7 neuGRID, outGRID and IMI Pharma-Cog. N. C. Fox is supported by Medical Research Council grants G0801306 and G0601846, NIH grant U01 AG024904, Alzheimer Research Trust grant ART/RF/2007/1 and the National Institute for Health Research. C. R. Jack is supported by National Institute on Aging grant AG11378 and the Alexander Family Alzheimer's Disease Research Professorship. P. M. Thompson was supported by NIH grants EB007813, EB008281, EB008432, HD050735, AG020098, P41 RR013642 and M01 RR000865.

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Author notes

  1. G. B. Frisoni gfrisoni@fatebenefratelli.it

Authors and Affiliations

  1. IRCCS Centro San Giovanni di Dio FBF, via Pilastroni 1, 25125, Brescia, Italy

    Giovanni B. Frisoni

  2. Dementia Research Center, UCL Institute of Neurology, Box 16, Queen Square, WC1N 3BG, London, UK

    Nick C. Fox

  3. Mayo Clinic, 200 1st Street SW, Rochester, 55905, MN, USA

    Clifford R. Jack Jr

  4. Alzheimer Center and Department of Neurology, VU University Medical Center, Postbus 7057, 1007 MB, Amsterdam, The Netherlands

    Philip Scheltens

  5. Department of Neurology, Laboratory of Neuro Imaging, 225E Neuroscience Research Building, 635 Charles Young Drive, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    Paul M. Thompson

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Competing interests

N. C. Fox has received payment for consultancy or for conducting studies from Abbott Laboratories, Elan Pharmaceuticals, Eisai, Eli Lilly, GE Healthcare, IXICO, Lundbeck, Pfizer, Sanofi-Aventis and Wyeth Pharmaceuticals. The other authors declare no competing interests.

Supplementary information

Supplementary Table 1

Rates of brain atrophy and ventricular enlargement in Alzheimer disease. (DOC 117 kb)

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Frisoni, G., Fox, N., Jack, C. et al. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 6, 67–77 (2010). https://doi.org/10.1038/nrneurol.2009.215

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