ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 255, Issue 4, pp 567-574

First online:

Volumetric MRI and cognitive measures in Alzheimer disease

Comparison of markers of progression
  • B. H. RidhaAffiliated withDementia Research Centre, Institute of Neurology, University College London Email author 
  • , V. M. AndersonAffiliated withDementia Research Centre, Institute of Neurology, University College London
  • , J. BarnesAffiliated withDementia Research Centre, Institute of Neurology, University College London
  • , R. G. BoyesAffiliated withDementia Research Centre, Institute of Neurology, University College London
  • , S. L. PriceAffiliated withDementia Research Centre, Institute of Neurology, University College London
  • , M. N. RossorAffiliated withDementia Research Centre, Institute of Neurology, University College London
  • , J. L. WhitwellAffiliated withDementia Research Centre, Institute of Neurology, University College LondonDept. of Radiology, Mayo Clinic
  • , L. JenkinsAffiliated withWyeth Pharmaceuticals
  • , R. S. BlackAffiliated withWyeth Pharmaceuticals
    • , M. GrundmanAffiliated withElan Pharmaceuticals, Inc.
    • , N. C. FoxAffiliated withDementia Research Centre, Institute of Neurology, University College London

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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.

Key words

Alzheimer's disease volumetric MRI measures cognitive scales clinical trials