title: Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer's disease.
abstract: BACKGROUND
  This study was designed to assess changes in brain volume and cognitive abilities in memantine-treated patients with Alzheimer's disease (AD) by using an exploratory, single-arm, delayed-start design.
  
  
  METHODS
  Cholinesterase inhibitor-treated patients with AD (N = 47; Mini-Mental State Examination score range: 15-23) were enrolled in an observational lead-in period (weeks: 1-24), followed by an open-label period of add-on memantine treatment (weeks: 25-48). The patients underwent magnetic resonance imaging at weeks 0 (baseline), 24 (immediately before memantine initiation), and 48 (endpoint), and a battery of neuropsychological tests at weeks 0, 24, 28, 36, and 48. The primary outcome measure was the annualized rate of change (%) in total brain volume (TBV) between the two study periods. Data were analyzed using paired t-tests.
  
  
  RESULTS
  There were no statistically significant differences in the rates of change in TBV, ventricular volume, or left hippocampal volume between the study periods; however, the memantine treatment period was associated with a significantly slower right hippocampal atrophy (-5.5% ± 12.0% vs -10.8% ± 7.2%; P = .038). Memantine treatment was also associated with superior performances on the Boston Naming Test (P = .034) and the Trail Making Test, Part B (P = .001), but also with a higher number of errors (i.e., repetitions and intrusions) on the California Verbal Learning Test. Memantine was found to be safe and well tolerated.
  
  
  CONCLUSIONS
  In this study, no difference in the rates of TBV change between the two periods was observed; however, memantine treatment was found to be associated with slowing of right hippocampal atrophy, and with improvement on one test of executive functioning as well as a test of confrontation naming ability. Trials using structural magnetic resonance imaging and a delayed-start design may be a feasible option for the assessment of treatments for AD.
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, and University of California San Francisco, San Francisco, CA, USA. Michael.Weiner@ucsf.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Carl
authors.initials: C
authors.lastname: Sadowsky
authors.forename: Judith
authors.initials: J
authors.lastname: Saxton
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hofbauer
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Graham
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Yu
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Li
authors.forename: Hai-An
authors.initials: HA
authors.lastname: Hsu
authors.forename: Joyce
authors.initials: J
authors.lastname: Suhy
authors.forename: Moshe
authors.initials: M
authors.lastname: Fridman
authors.forename: James L
authors.initials: JL
authors.lastname: Perhach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology*; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine