title: Chronic divalproex sodium use and brain atrophy in Alzheimer disease.
abstract: OBJECTIVE
  We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects.
  
  
  METHODS
  Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals.
  
  
  RESULTS
  There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ε4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (-10.9% and -12.4% vs -5.6% and -6.3%, and -3.5% vs -1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p < 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo = -2.0 ± 4.3, divalproex = -3.9 ± 4.0) (p = 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months.
  
  
  CONCLUSIONS
  Divalproex treatment was associated with accelerated brain volume loss over 1 year and perhaps with greater cognitive impairment. The long-term clinical effects of these changes are not known.
authors.affiliation: Banner Alzheimer's Institute, 901 E Willetta Street, Phoenix, AZ 85006, USA. Adam.fleisher@bannerhealth.com
authors.forename: A S
authors.initials: AS
authors.lastname: Fleisher
authors.forename: D
authors.initials: D
authors.lastname: Truran
authors.forename: J T
authors.initials: JT
authors.lastname: Mai
authors.forename: J B S
authors.initials: JB
authors.lastname: Langbaum
authors.forename: P S
authors.initials: PS
authors.lastname: Aisen
authors.forename: J L
authors.initials: JL
authors.lastname: Cummings
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.forename: M W
authors.initials: MW
authors.lastname: Weiner
authors.forename: R G
authors.initials: RG
authors.lastname: Thomas
authors.forename: L S
authors.initials: LS
authors.lastname: Schneider
authors.forename: P N
authors.initials: PN
authors.lastname: Tariot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D000704:Analysis of Variance; D001284:Atrophy / Q000209:etiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D004311:Double-Blind Method; D016503:Drug Delivery Systems / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid