Page 344 - merged

S084-3

Sodium Benzoate, A D-Amino Acid Oxidase (DAOA) Inhibitor, as A Cognitive
Enhancer

Hsien-Yuan Lane

China Medical University, Taiwan

Background/Objective: NMDA receptor (NMDAR) mediated neurotransmission plays a vital role
in cognitive function. D-serine acts as a full agonist at the NMDAR-glycine site. Sodium benzoate,
an inhibitor of D-amino acid oxidase (DAAO), can block the degradation of D-serine. We studied the
potential of sodium benzoate as a cognitive enhancer.

Method: We conducted two studies. The first was a 6-week, randomized, double-blind,
placebo-controlled trial in 52 patients with chronic schizophrenia who had been stabilized with
antipsychotic medications for 3 months or longer. Add-on treatment of 1 g/day of sodium benzoate or
placebo was given to the subject. Seven cognitive domains as recommended by the National Institute
of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia
(MATRICS) initiative were applied before and after the treatment. The second was a 24-week,
randomized, double-blind, placebo-controlled trial. Sixty patients with amnestic mild cognitive
impairment or mild Alzheimer's Disease (AD) were treated with 250-750 mg/day of sodium benzoate
or placebo. Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) (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.

Result: Six-week, 1-gm/day sodium benzoate adjunctive therapy significantly and safely improved
neurocognition subtests, including processing speed and visual learning in patients with
schizophrenia. Moreover, sodium benzoate brought a better improvement than placebo in ADAS-cog
at week 16, week 24, and endpoint), additional cognition composite, and global function (at week 16,
week 24, and endpoint) in patients with early-phase AD. Sodium benzoate was well-tolerated
without evident side-effects.

Conclusion: Inhibition of DAAO by sodium benzoate to enhance NMDAR-mediated
neurotransmission may improve cognitive function of patients with schizophrenia or early-phase AD.

Reference: Lane HY et al. Add-on treatment of benzoate for schizophrenia: a randomized,
double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013
Dec; 70(12):1267-1275.
Lin CH et al. Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer
disease: a randomized, double-blind, placebo-controlled trial. Biol Psychiatry. 2014
May ;75(9):678-685.