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Mild Cognitive Impairment Can Be Distinguished From Alzheimer Disease and Normal Aging for Clinical Trials
Michael Grundman, MD, MPH;
Ronald C. Petersen, PhD, MD;
Steven H. Ferris, PhD;
Ronald G. Thomas, PhD;
Paul S. Aisen, MD;
David A. Bennett, MD;
Norman L. Foster, MD;
Clifford R. Jack, Jr, MD;
Douglas R. Galasko, MD;
Rachelle Doody, MD, PhD;
Jeffrey Kaye, MD;
Mary Sano, PhD;
Richard Mohs, PhD;
Serge Gauthier, MD;
Hyun T. Kim, MS;
Shelia Jin, MD, MPH;
Arlan N. Schultz, MA;
Kimberly Schafer, MS;
Ruth Mulnard, RN, DNSc;
Christopher H. van Dyck, MD;
Jacobo Mintzer, MD;
Edward Y. Zamrini, MD;
Deborah Cahn-Weiner, PhD;
Leon J. Thal, MD; for the Alzheimer's Disease Cooperative Study
Arch Neurol. 2004;61:59-66.
Background Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD.
Objective To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial.
Design Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial.
Setting Memory disorder centers in the United States and Canada.
Patients A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0.
Main Outcome Measures Clinical, neuropsychologic, functional, neuroimaging, and genetic measures.
Results Mean ± SD Alzheimer's Disease Assessment Scale–Cognitive Subscale scores were 5.6 ± 3.3 for controls, 11.3 ± 4.4 for patients with MCI, 18.0 ± 6.2 for the AD CDR 0.5 group, and 25.2 ± 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E  4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD.
Conclusions Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.
From the Departments of Neurosciences (Drs Grundman, Thomas, Galasko, Jin, and Thal, Messrs Kim and Schultz, and Ms Schafer) and Family and Preventive Medicine (Dr Thomas), University of California, San Diego, La Jolla; Departments of Neurology (Dr Petersen) and Diagnostic Radiology (Dr Jack), Mayo Clinic and Foundation, Rochester, Minn; Department of Psychiatry, New York University School of Medicine, New York (Dr Ferris); Department of Neurology, Georgetown University, Washington, DC (Dr Aisen); Rush Alzheimer's Disease Center, Rush Presbyterian–St Luke's Medical Center, Chicago, Ill (Dr Bennett); Department of Neurology, University of Michigan, Ann Arbor (Dr Foster); Baylor College of Medicine Alzheimer's Disease Research Center, Houston, Tex (Dr Doody); Department of Neurology, Oregon Health & Science University and the Portland Veterans Affairs Medical Center, Portland (Dr Kaye); Department of Neurology, Columbia University, New York (Dr Sano); Lilly Research Laboratories, Eli Lilly & Co, Indianapolis, Ind (Dr Mohs); Alzheimer's Disease Research Unit at the McGill Centre for Studies in Aging, McGill University, Montreal, Quebec (Dr Gauthier); Brain Aging Research Unit, University of California, Irvine (Dr Mulnard); Department of Psychiatry, Yale University, New Haven, Conn (Dr van Dyck); Department of Psychiatry, Medical University of South Carolina, Charleston (Dr Mintzer); Department of Neurology, University of Alabama at Birmingham (Dr Zamrini); and Department of Psychiatry and Human Behavior, Brown University, Providence, RI (Dr Cahn-Weiner). Dr Doody has received research grants and honoraria from Eisai Inc and Pfizer Inc in the past.
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