title: AMPA potentiator treatment of cognitive deficits in Alzheimer disease.
abstract: OBJECTIVE
  To investigate the efficacy and safety of the positive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 in patients with mild to moderate Alzheimer disease (AD) (Mini-Mental State Examination scores 14 to 26).
  
  
  METHODS
  One hundred eighty-one patients were randomized to treatment in an 11-week, double-blind, placebo-controlled trial. Patients received either LY451395 0.2 mg BID for 28 days and 1.0 mg BID thereafter (n = 90) or placebo (n = 91). The primary outcome measurement was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) with several secondary outcome measurements: Clinician's Interview-Based Impression of Change, Trail Making Part A, Stylus Tapping Test, Single Digit Modality Test, and Neuropsychiatric Inventory (NPI).
  
  
  RESULTS
  Baseline demographics were similar between the two groups. Patients did not show any mean change from baseline in the ADAS-Cog after treatment with LY451395 for 4 weeks (p = 0.60) or 8 weeks (p = 0.83). The only secondary outcome measurement that showed changes from baseline compared with placebo was the NPI Total Score: p = 0.06 (marginal significance) after 4 weeks of treatment and p = 0.03 after 8 weeks of treatment. Ninety-two percent of LY451395-treated patients and 95% of placebo-treated patients completed the trial. Adverse events were experienced by 83% of LY451395-treated patients and 86% of placebo-treated patients, the majority of which were rated mild in severity.
  
  
  CONCLUSIONS
  Patients treated with LY451395 did not show a statistically significant separation from patients taking placebo on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the primary outcome measure.
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. aschappell@lilly.com
authors: A S
authors: AS
authors: Chappell
authors: C
authors: C
authors: Gonzales
authors: J
authors: J
authors: Williams
authors: M M
authors: MM
authors: Witte
authors: R C
authors: RC
authors: Mohs
authors: R
authors: R
authors: Sperling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D004311:Double-Blind Method; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; D018690:Excitatory Amino Acid Agonists; C512030:N-((2-(4'-(2-(methylsulfonyl)amino)ethyl)(1,1'-biphenyl)-4-yl)propyl)-2-propanesulfonamide; D010919:Placebos; D018091:Receptors, AMPA; D013449:Sulfonamides; D018698:Glutamic Acid