Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition

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 less than or equal to2 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.