1. Efficacy of Xanomeline in Alzheimer Disease: Cognitive Improvement Measured Using the Computerized Neuropsychological Test Battery (CNTB)
- Author
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Walter W. Offen, Neal R. Cutler, John J. Sramek, Neil C. Bodick, and Amy E. Veroff
- Subjects
Male ,medicine.medical_specialty ,Randomization ,Pyridines ,Muscarinic Agonists ,Neuropsychological Tests ,Placebo ,Muscarinic agonist ,Central nervous system disease ,chemistry.chemical_compound ,Cognition ,Double-Blind Method ,Alzheimer Disease ,Internal medicine ,Thiadiazoles ,Reaction Time ,medicine ,Humans ,Diagnosis, Computer-Assisted ,Aged ,Aged, 80 and over ,Psychotropic Drugs ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Neuropsychological test ,Middle Aged ,medicine.disease ,Surgery ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,chemistry ,Mental Recall ,Population study ,Female ,Geriatrics and Gerontology ,Alzheimer's disease ,Psychology ,Xanomeline ,Gerontology ,Follow-Up Studies - Abstract
The cognitive efficacy of the M1-selective muscarinic agonist xanomeline in mild-to-moderate Alzheimer disease (AD) was measured using the Computerized Neuropsychological Test Battery (CNTB) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) in this 17-center, double-blind, placebo-controlled study. Three hundred forty-three patients were randomly assigned to receive 25, 50, or 75 mg xanomeline tartrate or placebo three times daily (t.i.d.) for 24 weeks, followed by placebo for 4 weeks in a single-blind washout phase. Cognitive function was assessed at randomization and after 4, 8, 12, 24, and 28 weeks. Three hundred nineteen patients were included in an intent-to-treat (ITT) analysis; 209 completers had evaluable data at week 24. ITT analysis showed a significant (por = 0.05) dose-response trend and a significant (por = 0.05) between-group comparison favoring 75 mg t.i.d. over placebo for the CNTB summary score but not for the ADAS-cog. In the completer analysis, however, the ADAS-cog showed a significant (por = 0.05) dose-response trend and between-group comparison, whereas the CNTB Summary Score did not. The ADAS-cog was less sensitive to treatment effects in mildly impaired patients (ADAS-cog21) than in moderately impaired patients (ADAS-cogor = 21), whereas the CNTB was sensitive in the entire study population (mean ADAS-cog = 22.5+/-9.6). Significant (por = 0.05) beneficial treatment effects were seen in measures of simple reaction time and delayed verbal recall, which are included in the CNTB but not in the ADAS-cog. During the single-blind placebo washout period, the ADAS-cog score of the placebo group worsened dramatically (change of 2.63 points; por = 0.001), whereas the CNTB score remained stable (change of 1.04 points; p=0.694). Thus, the CNTB appears to be more objective than the ADAS-cog.
- Published
- 1998