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
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.