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Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment

From the Departments of Neurosciences (A.S.F., C.T., L.J.T.) and Family and Preventative Medicine (S.S., A.C.G.), University of California, San Diego; Departments of Neurology (R.C.P.) and Diagnostic Radiology (C.P.W., C.R.J.), Mayo Clinic College of Medicine, Rochester, MN; and Department of Neurology (P.S.A.), Georgetown University, Washington, DC.

Address correspondence and reprint requests to Dr. Adam S. Fleisher, Alzheimer's Disease Cooperative Study, 8950 Villa La Jolla Drive, Suite C227, La Jolla, CA 92037 afleisher{at}ucsd.edu

Objective: To compare volumetric MRI of whole brain and medial temporal lobe structures to clinical measures for predicting progression from amnestic mild cognitive impairment (MCI) to Alzheimer disease (AD).

Methods: Baseline MRI scans from 129 subjects with amnestic MCI were obtained from participants in the Alzheimer's Disease Cooperative Study group's randomized, placebo-controlled clinical drug trial of donepezil, vitamin E, or placebo. Measures of whole brain, ventricular, hippocampal, and entorhinal cortex volumes were acquired. Participants were followed with clinical and cognitive evaluations until formal criteria for AD were met, or completion of 36 months of follow-up. Logistic regression modeling was done to assess the predictive value of all MRI measures, risk factors such as APOE genotype, age, family history of AD, education, sex, and cognitive test scores for progression to AD. Least angle regression modeling was used to determine which variables would produce an optimal predictive model, and whether adding MRI measures to a model with only clinical measures would improve predictive accuracy.

Results: Of the four MRI measures evaluated, only ventricular volumes and hippocampal volumes were predictive of progression to AD. Maximal predictive accuracy using only MRI measures was obtained by hippocampal volumes by themselves (60.4%). When clinical variables were added to the model, the predictive accuracy increased to 78.8%. Use of MRI measures did not improve predictive accuracy beyond that obtained by cognitive measures alone. APOE status, MRI, or demographic variables were not necessary for the optimal predictive model. This optimal model included the Delayed 10-word list recall, New York University Delayed Paragraph Recall, and the Alzheimer's Disease Assessment Scale–Cognitive Subscale total score.

Conclusion: In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.

Abbreviations: AD = Alzheimer disease; ADAS = Alzheimer's Disease Assessment Scale; ADCS = Alzheimer's Disease Cooperative Study; ADCS-ADL = ADCS activities of daily living scale; CDR = Clinical Dementia Rating; ERC = entorhinal cortex; GDS = Global Deterioration Scale; LARS = least angle regression analysis; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; NINCDS-ADRDA = National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; ROC = receiver operating characteristic.

Deceased.

Supported by a grant from the National Institute on Aging (UO1 AG10483), The Institute for the Study of Aging, Pfizer Inc., and Eisai Inc.

Disclosure: The authors report no conflicts of interest.

Received April 12, 2007. Accepted in final form June 27, 2007.

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