title: Phase II crossover trial of varenicline in mild-to-moderate Alzheimer's disease.
abstract: BACKGROUND
  Evidence supports a role of α4β2 receptors in Alzheimer's disease (AD).
  
  
  METHODS
  This Korean, multicenter, double-blind, two-period (6 weeks each), crossover study randomized participants to the order in which they received varenicline (1 mg twice daily) and placebo. Assessments included AD Assessment Scale-Cognitive Subscale (ADAS-Cog) 75, Neuropsychiatric Inventory (NPI), adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS).
  
  
  RESULTS
  For varenicline versus placebo (n = 66 randomized), there was no significant difference in the week 6 least square (LS) mean ADAS-Cog 75 total score (primary endpoint; 18.07 vs. 18.49; p = 0.3873) and a slight worsening in the week 6 LS mean NPI (3.82 vs. 2.55; p = 0.0468), primarily driven by decreased appetite/eating. Common treatment-related AEs were nausea (23.3; 3.4%), vomiting (15.0%; 0) and decreased appetite (15.0; 6.8%).
  
  
  CONCLUSIONS
  Varenicline did not improve cognition, behavior or global change in this population. The most frequent varenicline-associated AEs were gastrointestinal; psychiatric AEs were rare and similar between the groups.
authors.affiliation: Department of Psychiatry, Asan Medical Center, Seoul, South Korea.
authors.forename: Seong Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Hans
authors.initials: H
authors.lastname: Rollema
authors.forename: Elias M
authors.initials: EM
authors.lastname: Schwam
authors.forename: Tom
authors.initials: T
authors.lastname: McRae
authors.forename: Sarah
authors.initials: S
authors.lastname: Dubrava
authors.forename: Janice
authors.initials: J
authors.lastname: Jacobsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D001552:Benzazepines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010919:Placebos; D011810:Quinoxalines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D010919:Placebos; D011810:Quinoxalines; D000068580:Varenicline