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.
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