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From the Aging and Dementia Imaging Research Laboratory, Department of Radiology (P.V., C.R.J.), Department of Health Sciences Research (H.J.W., S.D.W.), and Department of Neurology (D.S.K., R.C.P.), Mayo Clinic and Foundation, Rochester, MN; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; and University of California at San Francisco and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco, CA.
Address correspondence and reprint requests to Dr. Clifford R. Jack, Jr., Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905 jack.clifford{at}mayo.edu
Objective: To assess the correlations of both MRI and CSF biomarkers with clinical diagnosis and with cognitive performance in cognitively normal (CN) subjects and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD).
Methods: This is a cross-sectional study with data from the Alzheimer's Disease Neuroimaging Initiative, which consists of CN subjects, subjects with aMCI, and subjects with AD with both CSF and MRI. Baseline CSF (t-tau, Aβ1-42, and p-tau181P) and MRI scans were obtained in 399 subjects (109 CN, 192 aMCI, 98 AD). Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject.
Results: We found no significant correlation between CSF biomarkers and cognitive scores in any of the 3 clinical groups individually. Conversely, STAND scores correlated with both Clinical Dementia Rating–sum of boxes and Mini-Mental State Examination in aMCI and AD (p 
0.01). While STAND and all CSF biomarkers were predictors of clinical group membership (CN, aMCI, or AD) univariately (p < 0.001), STAND was more predictive than CSF both univariately and in combined models.
Conclusions: CSF and MRI biomarkers independently contribute to intergroup diagnostic discrimination and the combination of CSF and MRI provides better prediction than either source of data alone. However, MRI provides greater power to effect cross-sectional groupwise discrimination and better correlation with general cognition and functional status cross-sectionally. We therefore conclude that although MRI and CSF provide complementary information, MRI reflects clinically defined disease stage better than the CSF biomarkers tested.
Abbreviations: AD = Alzheimer disease; ADNI = Alzheimer's Disease Neuroimaging Initiative; aMCI = amnestic mild cognitive impairment; AUROC = area under the receiver operating characteristic curve; CDR-SB = Clinical Dementia Rating–sum of boxes score; CI = confidence interval; CN = cognitively normal; EBM = evidence-based medicine; EC = entorhinal cortex; MMSE = Mini-Mental State Examination; NFT = neurofibrillary tangle; POLR = proportional odds logistic regression; STAND = Structural Abnormality Index.
Received December 5, 2008. Accepted in final form April 20, 2009.
Supplemental data at www.neurology.org
See page 294
*Investigators of The Alzheimer's Disease Neuroimaging Initiative are listed at www.loni.ucla.edu\ADNI\Collaboration\ADNI_Manuscript_Citations.pdf.
Disclosure: Author disclosures are provided at the end of the article.
Related Article
Neurology 2009 73: 294-301.
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