Efficacy of xanomeline in Alzheimer disease: cognitive improvement measured using the Computerized Neuropsychological Test Battery (CNTB).

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 (p < or = 0.05) dose-response trend and a significant (p < or = 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 (p < or = 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-cog < 21) than in moderately impaired patients (ADAS-cog > or = 21), whereas the CNTB was sensitive in the entire study population (mean ADAS-cog = 22.5+/-9.6). Significant (p < or = 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; p < or = 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.

• Authors: A E Veroff, N C Bodick, W W Offen, J J Sramek, N R Cutler
• Journal: Alzheimer disease and associated disorders (Alzheimer Dis Assoc Disord) Vol. 12 Issue 4 Pg. 304-12 (Dec 1998) ISSN: 0893-0341 [Print] United States
• PMID: 9876958 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Muscarinic Agonists
• Psychotropic Drugs
• Pyridines
• Thiadiazoles
• xanomeline

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnosis, drug therapy)
• Cognition (drug effects)
• Diagnosis, Computer-Assisted
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Male
• Mental Recall (drug effects)
• Middle Aged
• Muscarinic Agonists (adverse effects, therapeutic use)
• Neuropsychological Tests
• Psychotropic Drugs (adverse effects, therapeutic use)
• Pyridines (adverse effects, therapeutic use)
• Reaction Time (drug effects)
• Thiadiazoles (adverse effects, therapeutic use)
• Treatment Outcome