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Volumetric MRI and cognitive measures in Alzheimer disease

Comparison of markers of progression

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Abstract

Background

Both cognitive tests and MRI-based measures have been suggested as outcomes in trials assessing disease-modifying therapies in Alzheimer's disease (AD).

Objective

To compare changes in longitudinal MRI measures with changes in performance on cognitive tests routinely used in AD clinical trials.

Method

Fifty-two subjects from the placebo-arm of a clinical trial in mild-to-moderate AD had volumetric T1-weighted scans and cognitive tests including the Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale, Disability Assessment for Dementia, AD Cooperative Study-Clinical Global Impression of Change and Clinical Dementia Rating at baseline and one-year later. Rates of brain atrophy and ventricular enlargement were measured using the boundary shift integral. Hippocampal (Hc) atrophy was calculated from manual volume measurements. The relationships between MRI and cognitive measures were investigated.

Results

Rates of brain atrophy and/or ventricular enlargement were correlated with declining performance on cognitive scales. The strongest association was between brain atrophy rate and MMSE decline (r = 0.59, p < 0.0001). Hc atrophy rate was not significantly correlated with any of the cognitive scales.

Conclusion

The lack of correlation between Hc atrophy and cognitive scales may reflect a combination of: the extensive functional damage to the Hc by the time AD is clinically established, the greater influence of ongoing cortical degeneration, and errors in Hc outlining. The strong correlations between brain atrophy and ventricular enlargement, and cognitive scales probably reflect the correspondence between these measures of overall cerebral loss and global cognitive measures in the moderate stages of AD.

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Author information

Author notes

  1. J. L. Whitwell PhD

    Present address: Dept. of Radiology, Mayo Clinic, Rochester, MN, USA

Authors and Affiliations

  1. Dementia Research Centre, Institute of Neurology, University College London, 8-11 Queen Square, London, WC1N 3BG, UK

    B. H. Ridha MRCP, V. M. Anderson PhD, BSc, J. Barnes PhD, MA, R. G. Boyes ME, S. L. Price BSc, M. N. Rossor MD, FRCP, J. L. Whitwell PhD & N. C. Fox MD, MRCP

  2. Wyeth Pharmaceuticals, Collegeville, PA, USA

    L. Jenkins PhD & R. S. Black MD

  3. Elan Pharmaceuticals, Inc., Collegeville, PA, USA

    M. Grundman MD, MPH

Authors
  1. B. H. Ridha MRCP
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  2. V. M. Anderson PhD, BSc
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  3. J. Barnes PhD, MA
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  4. R. G. Boyes ME
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  5. S. L. Price BSc
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  6. M. N. Rossor MD, FRCP
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  7. J. L. Whitwell PhD
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  8. L. Jenkins PhD
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  9. R. S. Black MD
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  11. N. C. Fox MD, MRCP
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Corresponding author

Correspondence to B. H. Ridha MRCP.

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Disclosure

Sponsored by Elan Pharmaceuticals, Inc., and Wyeth Research. Drs. Fox and Rossor have received honoraria from Elan Pharmaceuticals, Inc., and Wyeth Research. Dr Black is an employee of, holds equity in excess of $10.000 in, and has received honoraria in excess of $10.000 from Wyeth Research. Dr Grundman is an employee of Elan Pharmaceuticals, Inc., and holds equity in its parent company, Elan Corporation plc.

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Ridha, B.H., Anderson, V.M., Barnes, J. et al. Volumetric MRI and cognitive measures in Alzheimer disease. J Neurol 255, 567–574 (2008). https://doi.org/10.1007/s00415-008-0750-9

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  • DOI: https://doi.org/10.1007/s00415-008-0750-9

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