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

• Published in: Neuropsychiatric disease and treatment Vol. 16; pp. 509 - 518
• Main Authors: Lin, Chieh-Hsin, Yang, Hui-Ting, Chen, Ping-Kun, Wang, Shi-Heng, Lane, Hsien-Yuan
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2020; Dove; Dove Medical Press
• Subjects: Alzheimer's disease; Amino acid oxidase; Amino acids; Antioxidants; Antipsychotics; behavioral and psychological symptoms of dementia (bpsd); Catalase; Clinical trials; Cognitive ability; D-Alanine; d-amino acids oxidase (daao) inhibitor; D-Amino-acid oxidase; D-Serine; Dementia; Dementia disorders; Double-blind studies; Drug dosages; FDA approval; Free radicals; Gender; Glycine; Hospitals; L-Alanine; L-Serine; Laboratories; n-methyl-d-aspartate; Neurodegenerative diseases; Original Research; Oxidative stress; Peripheral blood; Potassium; Precision medicine; Psychiatrists; Psychotropic drugs; Sample size; Schizophrenia; Sodium; Sodium benzoate; Superoxide dismutase; United States > US; BPSD; behavioral and psychological symptoms of dementia; sodium benzoate; DAAO; inhibitor; D-amino acids oxidase; precision medicine; N-methyl-D-aspartate
• ISSN: 1176-6328; 1178-2021; 1178-2021
• DOI: 10.2147/NDT.S234371

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. 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. 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. 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. The trial was registered online (https://clinicaltrials.gov/ct2/show/NCT02103673).