Precision medicine of sodium benzoate for the treatment of behavioral and psychological symptoms of dementia (BPSD)

Chieh Hsin Lin, Hui Ting Yang, Ping Kun Chen, Shi Heng Wang, Hsien Yuan Lane

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)509-518
Number of pages10
JournalNeuropsychiatric Disease and Treatment
Publication statusPublished - Jan 1 2020


  • Behavioral and psychological symptoms of dementia
  • BPSD
  • D-amino acids oxidase
  • DAAO
  • Inhibitor
  • N-methyl-D-aspartate
  • Precision medicine
  • Sodium benzoate

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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