PMID- 24074637
OWN - NLM
STAT- MEDLINE
DCOM- 20141204
LR  - 20220317
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 75
IP  - 9
DP  - 2014 May 1
TI  - Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase 
      Alzheimer disease: a randomized, double-blind, placebo-controlled trial.
PG  - 678-85
LID - S0006-3223(13)00739-7 [pii]
LID - 10.1016/j.biopsych.2013.08.010 [doi]
AB  - BACKGROUND: N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is 
      vital for learning and memory. Hypofunction of NMDAR has been reported to play a 
      role in the pathophysiology of Alzheimer disease (AD), particularly in the early 
      phase. Enhancing NMDAR activation might be a novel treatment approach. One of the 
      methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by 
      blocking their metabolism. This study examined the efficacy and safety of sodium 
      benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild 
      cognitive impairment and mild AD. METHODS: We conducted a randomized, 
      double-blind, placebo-controlled trial in four major medical centers in Taiwan. 
      Sixty patients with amnestic mild cognitive impairment or mild AD were treated 
      with 250-750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's 
      Disease Assessment Scale-cognitive subscale (the primary outcome) and global 
      function (assessed by Clinician Interview Based Impression of Change plus 
      Caregiver Input) were measured every 8 weeks. Additional cognition composite was 
      measured at baseline and endpoint. RESULTS: Sodium benzoate produced a better 
      improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive 
      subscale (p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, 
      respectively), additional cognition composite (p = .007 at endpoint) and 
      Clinician Interview Based Impression of Change plus Caregiver Input (p = .015, 
      .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate 
      was well-tolerated without evident side-effects. CONCLUSIONS: Sodium benzoate 
      substantially improved cognitive and overall functions in patients with 
      early-phase AD. The preliminary results show promise for D-amino acid oxidase 
      inhibition as a novel approach for early dementing processes.
CI  - Copyright (c) 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Lin, Chieh-Hsin
AU  - Lin CH
AD  - Institute of Clinical Medical Science, China Medical University, Taichung, 
      Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang 
      Gung University College of Medicine, Kaohsiung, Taiwan.
FAU - Chen, Ping-Kun
AU  - Chen PK
AD  - Institute of Clinical Medical Science, China Medical University, Taichung, 
      Taiwan; Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang 
      Gung University College of Medicine, Kaohsiung, Taiwan; Department of Neurology, 
      Lin-Shin Hospital, Taichung, Taiwan.
FAU - Chang, Yue-Cune
AU  - Chang YC
AD  - Department of Mathematics, Tamkang University, Taipei, Taiwan.
FAU - Chuo, Liang-Jen
AU  - Chuo LJ
AD  - Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
FAU - Chen, Yan-Syun
AU  - Chen YS
AD  - Department of Mathematics, Tamkang University, Taipei, Taiwan; Department of 
      Psychiatry, China Medical University Hospital, Taichung, Taiwan.
FAU - Tsai, Guochuan E
AU  - Tsai GE
AD  - Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California.
FAU - Lane, Hsien-Yuan
AU  - Lane HY
AD  - Institute of Clinical Medical Science, China Medical University, Taichung, 
      Taiwan; Department of Psychiatry, China Medical University Hospital, Taichung, 
      Taiwan. Electronic address: hylane@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130925
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nootropic Agents)
RN  - EC 1.4.3.3 (D-Amino-Acid Oxidase)
RN  - OJ245FE5EU (Sodium Benzoate)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*drug therapy
MH  - Cognition/drug effects
MH  - Cognitive Dysfunction/*drug therapy
MH  - D-Amino-Acid Oxidase/antagonists & inhibitors
MH  - Disease Progression
MH  - Double-Blind Method
MH  - Enzyme Inhibitors/therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Nootropic Agents/adverse effects/*therapeutic use
MH  - Severity of Illness Index
MH  - Sodium Benzoate/adverse effects/*therapeutic use
MH  - Taiwan
MH  - Time Factors
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Alzheimer disease
OT  - D-amino acids oxidase (DAAO) inhibitor
OT  - N-methyl-D-aspartate
OT  - clinical trial
OT  - mild cognitive impairment
OT  - sodium benzoate
EDAT- 2013/10/01 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/10/01 06:00
PHST- 2013/05/29 00:00 [received]
PHST- 2013/07/25 00:00 [revised]
PHST- 2013/08/05 00:00 [accepted]
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0006-3223(13)00739-7 [pii]
AID - 10.1016/j.biopsych.2013.08.010 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2014 May 1;75(9):678-85. doi: 10.1016/j.biopsych.2013.08.010. 
      Epub 2013 Sep 25.