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Precision Medicine of Sodium Benzoate for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)

Authors Lin CH, Yang HT, Chen PK, Wang SH, Lane HY

Received 11 October 2019

Accepted for publication 9 February 2020

Published 20 February 2020 Volume 2020:16 Pages 509—518


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yuping Ning

Chieh-Hsin Lin,1– 3 Hui-Ting Yang,4 Ping-Kun Chen,5,6 Shi-Heng Wang,7 Hsien-Yuan Lane2,8,9

1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 3School of Medicine, Chang Gung University, Taoyuan, Taiwan; 4School of Food Safety, Taipei Medical University, Taipei, Taiwan; 5School of Medicine, China Medical University, Taichung, Taiwan; 6Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 7Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan; 8Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 9Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan

Correspondence: Hsien-Yuan Lane
Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan

Objective: Behavioral and psychological symptoms of dementia (BPSD) are associated with poorer prognosis of dementia. A 24-week study demonstrated that sodium benzoate, a D-amino acid oxidase (DAAO) inhibitor, surpassed placebo in improving cognitive function in early-phase Alzheimer’s disease; however, benzoate did not excel placebo in another 6-week study on BPSD. The current study examined whether the precision medicine approach was able to identify specific individuals with BPSD who could benefit from benzoate treatment.
Methods: In the randomized, double-blind, placebo-controlled, 6-week trial, 97 patients with BPSD were allocated to receive 250– 1500 mg/day of sodium benzoate or placebo. Cognitive function was measured by the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) and behavioral and psychological symptoms were mainly measured by Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). DAAO level, amino acids (L-serine, D-serine, L-alanine, and D-alanine, glycine), and two antioxidants (catalase, superoxide dismutase) were assayed in peripheral blood.
Results: After benzoate treatment, DAAO inhibition was correlated with ADAS-cog decrease (p = 0.034), while baseline DAAO level was correlated with baseline BEHAVE-AD score. Multiple linear regression analyses showed that cognitive improvement after benzoate treatment was correlated with DAAO decrease, female gender, younger age, BMI, baseline BPSD severity, and antipsychotic use.
Conclusion: The finding suggests that sodium benzoate may have potential to benefit cognitive function in a fraction of BPSD patients after 6 weeks of treatment. Of note, the precision medicine approach may be helpful for identifying individuals who could respond to benzoate. More studies are warranted to confirm the preliminary findings.
Trial Registration: The trial was registered online (

Keywords: behavioral and psychological symptoms of dementia, BPSD, N-methyl-D-aspartate, D-amino acids oxidase, DAAO, inhibitor, sodium benzoate, precision medicine

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