PAPER

Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease

O L Lopez^1,2,3, J T Becker^1,2,3, S Wisniewski^1,4, J Saxton^1,2, D I Kaufer^1,2,3 and S T DeKosky^1,2,3

¹ Alzheimer's Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
² Department of Psychiatry
³ Department of Neurology
⁴ Department of Epidemiology

Correspondence to:
Correspondence to:
Dr O L Lopez, Neuropsychology Research Program, 3501 Forbes Avenue, Suite 830, Pittsburgh, PA 15213, USA

Objective: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD).

Methods: The short and long term effects of CEIs were evaluated in 135 patients with probable Alzheimer's disease relative to 135 patients who were never exposed to CEIs matched by age, education, duration of the symptoms, and cognitive status. We measured 1 year change in cognitive and functional performance, and the likelihood of arriving at each of four end points: (1) mini mental state examination (MMSE) of 9 or lower, (2) Blessed dementia rating scale for activities of daily living of 12 or higher, (3) nursing home admission, and (4) death, over an average 3 years of observation (36.7 (SD 21.5) months).

Results: Patients on CEIs were better cognitively and functionally after 1 year compared with those patients who never used CEIs. A proportional hazard analysis with CEI use as a time dependent covariate showed that the use of CEIs decreased the risk of nursing home admission. There was no association, however, between use of CEIs and time to cognitive and functional end points, or to death.

Conclusions: This observational study showed that there was an initial cognitive and functional benefit from the use of CEIs in Alzheimer's disease, which waned as the disease progressed. However, the results suggest that there is a long term beneficial effect of the use of CEIs, as indicated by the delay in adsmission to nursing homes.

Keywords: cholinesterase inhibitors; dementia; Alzheimer's disease

Abbreviations: CEIs, cholinesterase inhibitors; MMSE, mini mental state examination; HDRS, Hamilton depression rating scale; DSM-IV, statistical manual of mental disorders, fourth edition; EPS, extrapyramidal signs; BDRS, Blessed dementia rating scale; MDRS, Mattis dementia rating scale; CDR, clinical dementia rating; HRS, Hachinski rating scale;

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