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Abstract
Objective: To compare the annual change in MRI and CSF biomarkers in cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer disease (AD). Comparisons were based on intergroup discrimination, correlation with concurrent cognitive/functional changes, relationships to APOE genotype, and sample sizes for clinical trials.
Methods: We used data from the Alzheimer's Disease Neuroimaging Initiative study consisting of CN, aMCI, and AD cohorts with both baseline and 12-month follow-up CSF and MRI. The annual change in CSF (total-tau [t-tau], Aβ1-42) and MRI (change in ventricular volume) was obtained in 312 subjects (92 CN, 149 aMCI, 71 AD).
Results: There was no significant average annual change in either CSF biomarker in any clinical group except t-tau in CN; moreover, the annual change did not differ by clinical group in pairwise comparisons. In contrast, annual increase in ventricular volume increased in the following order, AD > aMCI > CN, and differences were significant between all clinical groups in pairwise comparisons. Ventricular volume increase correlated with concurrent worsening on cognitive/functional indices in aMCI and AD whereas evidence of a similar correlation with change in CSF measures was unclear. The annual changes in MRI differed by APOE ε4 status overall and among aMCI while annual changes in CSF biomarkers did not. Estimated sample sizes for clinical trials are notably less for MRI than the CSF or clinical measures.
Conclusions: Unlike the CSF biomarkers evaluated, changes in serial structural MRI are correlated with concurrent change on general cognitive and functional indices in impaired subjects, track with clinical disease stage, and are influenced by APOE genotype.
Footnotes
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Supplemental data at www.neurology.org
Data used in the preparation of this article were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu\ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete list of ADNI investigators is available in appendix e-1 at www.neurology.org.
Study funding: Supported by NIH grant AG11378; a Robert H. Smith Family Foundation Research Fellowship; the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation, USA; and Opus building NIH grant C06 RR018898. The Foundation for the National Institutes of Health (www.fnih.org) coordinates the private sector participation of the $60 million ADNI public-private partnership that was begun by the National Institute on Aging (NIA) and supported by the National Institutes of Health. To date, more than $27 million has been provided to the Foundation for NIH by Abbott, AstraZeneca AB, Bayer Schering PharmaAG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Merck & Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-LaRoche, Schering-Plough, Synarc Inc., and Wyeth, as well as nonprofit partners the Alzheimer's Association and the Institute for the Study of Aging.
Disclosure: Author disclosures are provided at the end of the article.
Received November 21, 2009. Accepted in final form March 10, 2010.
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