Lon S Schneider1, Philip S Insel, Michael W Weiner. 1. Department of Psychiatry and the Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. lschneid@usc.edu
Abstract
OBJECTIVES: To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. DESIGN: Cohort study. SETTING: The 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: Outpatients with MCI and AD in ADNI. MAIN OUTCOME MEASURES: The AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). RESULTS: A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. CONCLUSIONS: Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration-approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. STUDY REGISTRATION: clinicalTrials.gov Identifier: NCT00106899.
OBJECTIVES: To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. DESIGN: Cohort study. SETTING: The 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: Outpatients with MCI and AD in ADNI. MAIN OUTCOME MEASURES: The AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). RESULTS: A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-ADpatients were treated with ChEIs and 11.4% of MCI patients and 45.7% of ADpatients with memantine at entry. Mild-cognitive-impairmentpatients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-diseasepatients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. CONCLUSIONS: Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration-approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. STUDY REGISTRATION: clinicalTrials.gov Identifier: NCT00106899.
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