Neuropsychiatric Disease and Treatment (Feb 2020)
Precision Medicine of Sodium Benzoate for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)
Abstract
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, TaiwanCorrespondence: Hsien-Yuan LaneDepartment of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, TaiwanEmail [email protected]: 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 (https://clinicaltrials.gov/ct2/show/NCT02103673).Keywords: behavioral and psychological symptoms of dementia, BPSD, N-methyl-D-aspartate, D-amino acids oxidase, DAAO, inhibitor, sodium benzoate, precision medicine
