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NEUROLOGY 2006;67:467-473
© 2006 American Academy of Neurology

Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI

Martha Storandt, PhD, Elizabeth A. Grant, PhD, J. Philip Miller and John C. Morris, MD

From the Departments of Psychology (M.S.) and Neurology and Pathology and Immunology (J.C.M.), Division of Biostatistics (E.A.G., J.P.M.), and Alzheimer Disease Research Center (M.S., E.A.G., J.P.M., J.C.M.), Washington University, St. Louis, MO.

Address correspondence and reprint requests to Dr. John C. Morris, Alzheimer Disease Research Center, 4488 Forest Park Avenue, Suite 160, St. Louis, MO 63108; e-mail: morrisj{at}abraxas.wustl.edu

Objectives: To compare the natural history of individuals classified with mild cognitive impairment (MCI) in accordance with original criteria to the natural history of individuals classified with revised MCI criteria.

Methods: The authors compared the rates of progression in 32 individuals with amnestic MCI and in 90 people with MCI according to revised criteria that allow nonamnestic deficits with progression in 276 individuals who were too minimally impaired (pre-MCI) to meet either MCI criteria. All individuals in this study were determined clinically to be very mildly cognitively impaired with a Clinical Dementia Rating (CDR) of 0.5.

Results: Rates of progression for the two MCI groups were similar with a decline of almost 0.50 SD per year on a psychometric composite. Decline was less (0.23 SD) in the pre-MCI group. Median survival time to CDR 1 (mild dementia) was comparable for the original (95% CI: 3.79 to 4.07 years) and revised (95% CI: 3.29 to 5.40) criteria MCI groups but approximately twice as long in the pre-MCI group (95% CI: 6.72 to 8.93). All cases from the amnestic MCI criteria group with neuropathologic diagnoses met criteria for Alzheimer disease as did more than 90% in the other two groups.

Conclusions: Mild cognitive impairment as originally and currently defined is usually early stage Alzheimer disease, which can begin with a cognitive deficit other than memory. It is possible to identify Alzheimer disease at an even earlier stage than mild cognitive impairment by focusing on intraindividual change rather than comparison with group norms.


Supported by National Institute on Aging grants P01 AG03991 and P50 AG05681.

Disclosure: The authors report no conflicts of interest.

Received October 25, 2005. Accepted in final form April 11, 2006.




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