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Matthias H. Tabert, PhD; Jennifer J. Manly, PhD; Xinhua Liu, PhD; Gregory H. Pelton, MD; Sara Rosenblum, BS; Marni Jacobs, BA; Diana Zamora, BA; Madeleine Goodkind, BA; Karen Bell, MD; Yaakov Stern, PhD; D. P. Devanand, MD

Arch Gen Psychiatry. 2006;63:916-924.

Context  The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established.

Objectives  To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion.

Design  Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures.

Setting  Memory disorders clinic.

Participants  One hundred forty-eight patients reporting memory problems and 63 group-matched controls.

Main Outcome Measure  A consensus diagnosis of probable AD.

Results  At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 ± 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale–Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P<.0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%.

Conclusions  Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

Author Affiliations: Department of Biological Psychiatry, New York State Psychiatric Institute (Drs Tabert, Pelton, and Devanand and Mss Rosenblum, Jacobs, Zamora, and Goodkind), Departments of Psychiatry (Drs Tabert, Pelton, Stern, and Devanand) and Neurology (Drs Manly, Pelton, Bell, Stern, and Devanand), and the Gertrude H. Sergievsky Center (Drs Tabert, Manly, Pelton, Bell, Stern, and Devanand), Columbia University College of Physicians and Surgeons, and Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Tabert, Manly, Pelton, Bell, Stern, and Devanand) and Department of Biostatistics, Mailman School of Public Health (Dr Liu), Columbia University, New York, NY.

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