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From the Department of Biological Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University (D.P.D., G.P., S.S., G.H.P., R.M., Y.S., M.H.T.); Gertrude H. Sergievsky Center and the Departments of Neurology (D.P.D., G.H.P., L.S.H., R.M., Y.S.) and Radiology (A.K.), College of Physicians and Surgeons, Columbia University; Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University (D.P.D., L.S.H., R.M., Y.S.); Department of Biostatistics, Columbia University, New York, NY (X.L.); Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, NY (S.D.S., S.S., H.R., M.J.d.L.); and the Nathan Kline Institute, Orangeburg, NY (S.D.S., H.R., M.J.d.L.).
Address correspondence and reprint requests to Dr Devanand, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 126, New York, NY 10032; e-mail: dpd3{at}columbia.edu
Objective: To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).
Methods: Baseline brain MRI was performed in 139 patients with MCI, broadly defined, and 63 healthy controls followed for an average of 5 years (range 1 to 9 years).
Results: Hippocampal and entorhinal cortex volumes were each largest in controls, intermediate in MCI nonconverters, and smallest in MCI converters to AD (37 of 139 patients converted to AD). In separate Cox proportional hazards models, covarying for intracranial volume, smaller hippocampal volume (risk ratio [RR] 3.62, 95% CI 1.93 to 6.80, p < 0.0001), and entorhinal cortex volume (RR 2.43, 95% CI 1.56 to 3.79, p < 0.0001) each predicted time to conversion to AD. Similar results were obtained for hippocampal and entorhinal cortex volume in patients with MCI with Mini-Mental State Examination (MMSE) scores 
27 out of 30 (21% converted to AD) and in the subset of patients with amnestic MCI (35% converted to AD). In the total patient sample, when both hippocampal and entorhinal volume were entered into an age-stratified Cox model with sex, MMSE, education, and intracranial volume, smaller hippocampal volume (RR 2.21, 95% CI 1.14 to 4.29, p < 0.02) and entorhinal cortex volume (RR 2.48, 95% CI 1.54 to 3.97, p < 0.0002) predicted time to conversion to AD. Similar results were obtained in a Cox model that also included Selective Reminding Test (SRT) delayed recall and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol as predictors. Based on logistic regression models in the 3-year follow-up sample, for a fixed specificity of 80%, the sensitivities for MCI conversion to AD were as follows: age 43.3%, MMSE 43.3%, age + MMSE 63.7%, age + MMSE + SRT delayed recall + WAIS-R Digit Symbol 80.6% (79.6% correctly classified), hippocampus + entorhinal cortex 66.7%, age + MMSE + hippocampus + entorhinal cortex 76.7% (85% correctly classified), age + MMSE + SRT delayed recall + WAIS-R Digit Symbol + hippocampus + entorhinal cortex 83.3% (86.8% correctly classified).
Conclusions: Smaller hippocampal and entorhinal cortex volumes each contribute to the prediction of conversion to Alzheimer disease. Age and cognitive variables also contribute to prediction, and the added value of hippocampal and entorhinal cortex volumes is small. Nonetheless, combining these MRI volumes with age and cognitive measures leads to high levels of predictive accuracy that may have potential clinical application.
Supported in part by grants AG17761, AG12101, MH55735, MH35636, MH55646, P50 AG08702, and P30 AG08051 from the National Institute on Aging and the National Institute of Mental Health.
Disclosure: The authors report no conflicts of interest.
Received April 4, 2006. Accepted in final form November 10, 2006.
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