TY - JOUR

T1 - Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate alzheimer's disease

AU - Wilkinson, David

AU - Schindler, Rachel

AU - Schwam, Elias

AU - Waldemar, Gunhild

AU - Jones, Roy W

AU - Gauthier, Serge

AU - Lopez, Oscar L

AU - Cummings, Jeffrey

AU - Xu, Yikang

AU - Feldman, Howard H

N1 - Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Disease Progression; Double-Blind Method; Female; Humans; Indans; Male; Middle Aged; Neuropsychological Tests; Nootropic Agents; Odds Ratio; Piperidines; Treatment Outcome

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer's disease (AD). METHODS: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician's Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients. CONCLUSION: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients.

AB - BACKGROUND: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer's disease (AD). METHODS: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician's Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients. CONCLUSION: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients.

U2 - 10.1159/000241877

DO - 10.1159/000241877

M3 - Journal article

C2 - 19786776

VL - 28

SP - 244

EP - 251

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

SN - 1420-8008

IS - 3

ER -