Volume 53, Issue 1 p. 83-87

Alteration of a Clinically Meaningful Outcome in the Natural History of Alzheimer's Disease by Cholinesterase Inhibition

Oscar L. Lopez MD

Oscar L. Lopez MD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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James T. Becker PhD

James T. Becker PhD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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Judith Saxton PhD

Judith Saxton PhD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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Robert A. Sweet MD

Robert A. Sweet MD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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William Klunk MD, PhD

William Klunk MD, PhD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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Steven T. DeKosky MD

Steven T. DeKosky MD

From the * Alzheimer's Disease Research Center and Departments of, Psychiatry, Neurology, and § Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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First published: 22 December 2004
Citations: 75
Address correspondence to Oscar L. Lopez, MD, Neuropsychology Research Program, 3600 Forbes Avenue, Suite 502, Pittsburgh, PA 15213. E-mail: [email protected]

Dr. Lopez has received honoraria from Eisai/Pfizer and Forest Laboratories. Dr. Dekosky serves on the advisory boards for Astra-Zeneca, Cephalon, and Eisai/Pfizer and as a consultant for Forest Laboratories, Eisai/Pfizer, Cephalon, Janssen, Novartis, Astra-Zeneca, Daiichi, and Teva Pharmaceuticals. This study was supported by Grants AG03705 and AG05133 from the National Institute on Aging. Dr. Becker is a recipient of the Research Scientist Development Award (Level II) (K02-MH01077).

Abstract

Objectives: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes.

Design: Cross-sectional and longitudinal study.

Setting: Referral dementia clinic.

Participants: One hundred thirty-five matched pairs of patients with probable AD.

Measurements: The risk of AD patients being classified as slow progressors (Mini-Mental State Examination (MMSE) score change ≤2 at 1-year follow-up) was examined as a function of treatment with CEIs. A logistic regression analysis, controlling for age, sex, education level, MMSE score, Blessed Dementia Rating Scale (BDRS) for activities of daily living (ADLs), extrapyramidal signs, psychosis, major depression, and use of antidepressants, antipsychotics, and sedative/hypnotics determined the factors that best predict slow progression and nursing home admission.

Results: Eighty-one (60%) of the patients on CEIs and 53 (39%) of the patients who never used CEIs were considered slow progressors (P=.001) at 1-year follow-up. Slow progression was associated only with CEI use (relative risk (RR)=2.45, 95% confidence interval (CI)=1.45–4.16), and sedative/hypnotics use was associated with a MMSE change of 3 points or more (RR=0.35, 95% CI=0.13–0.93). CEI use had a protective effect on nursing home admission (RR=0.095, 95% CI=0.03–0.30), whereas higher scores on the BDRS for ADLs increased risk of admission at 24- and 36-month follow-up.

Conclusion: CEI use had a clinically meaningful effect on the natural history of AD. Patients taking CEIs were 2.5 times more likely to progress slowly and had a lower risk of nursing home admission after 2 years, even after controlling for multiple factors that can alter the course of the disease, and a slower rate of decline during the first year of follow-up.