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

ABSTRACT: 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 (https://clinicaltrials.gov/ct2/show/NCT02103673).

SUBMITTER: Lin CH

PROVIDER: S-EPMC7039065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Lin Chieh-Hsin CH Yang Hui-Ting HT Chen Ping-Kun PK Wang Shi-Heng SH Lane Hsien-Yuan HY

Neuropsychiatric disease and treatment 20200220

<h4>Objective</h4>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 c ...[more]

PMID: 32110025

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Project description:ImportanceFemale gender is a major risk factor for dementia; however, gender has not yet been adequately addressed by clinical trials. A recent study demonstrated that sodium benzoate, a D-amino acid oxidase inhibitor, improved cognitive function in early-phase Alzheimer disease.ObjectiveTo examine the potential gender difference in the effects of benzoate treatment on the behavioral and psychological symptoms of dementia (BPSD).Design, setting, and participantsThis post hoc secondary analysis used data from a randomized, double-masked, placebo-controlled trial conducted in 3 major medical centers in Taiwan and enrolled 97 patients with BPSD. Data were analyzed between February 2014 and November 2017.InterventionsSix weeks of treatment of 250 to 1500 mg/d of sodium benzoate or placebo.Main outcomes and measuresThe primary outcome measures were Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) and Behavioral Pathology in Alzheimer Disease Rating Scale (BEHAVE-AD) scores.ResultsAmong 97 total participants (62 [64%] women; mean [SD] age, 75.4 [7.7] years), 49 patients (30 women and 19 men) were randomized to sodium benzoate, and 48 (32 women and 16 men) were randomized to placebo. Among 62 women, 6-week benzoate treatment significantly surpassed placebo in the effects on ADAS-cog performance (mean [SD] difference in score between baseline and end point, -3.1 [6.4] points vs 0 [4.5] points; Cohen d = 0.56; P = .04) but not BEHAVE-AD performance. In contrast, among 35 men, the 2 treatment groups did not differ significantly in both ADAS-cog and BEHAVE-AD scores. Compared with placebo, benzoate treatment also increased estradiol to follicle-stimulating hormone ratios among women (mean [SD] difference between baseline and end point, 0 [0.2] vs -0.1 [0.3]; P = .03).Conclusions and relevanceThese findings suggest that benzoate treatment may improve cognitive function in women with later-phase dementia. In the future, longer dose-finding trials are warranted to further clarify the efficacy of benzoate for later-phase dementia and investigate the role of sex hormones and other factors in the pathogenesis of dementia.Trial registrationClinicalTrials.gov Identifier: NCT02103673.

Project description:Background: Dementia is a global health concern, causing serious health and socioeconomic burdens with population aging. The associated symptoms of dementia, called behavioral and psychological symptoms of dementia (BPSD), are factors contributing to the socioeconomic burden of dementia. Recently, herbal medicine (HM) has attracted attention as a potential complementary therapy for BPSD. Therefore, this systematic review was aimed at analyzing the effectiveness (or efficacy), safety, and research status of HM in BPSD management through a comprehensive review. Methods: Thirteen electronic databases were searched comprehensively. Related clinical studies published until December 28, 2020, were collected. The methodological quality was evaluated using tools such as the Cochrane Collaboration's risk of bias tool according to the study design. The effectiveness (or efficacy) was analyzed for randomized controlled trials (RCTs) only, and when sufficient homogeneity was assured, effect estimates were presented as mean difference (MD) and risk ratio (RR), with 95% confidence interval (CIs), through a meta-analysis. Results: A total of 52 clinical studies, including 36 RCTs, were included in this review. As an adjunctive therapy, HM showed statistically significant benefits in BPSD severity assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (combined with psychotropic drugs: MD = -3.48, 95% CI: -3.96 to -2.99; with anti-dementia drugs: MD = -2.81, 95% CI: -3.17 to -2.45) and Neuropsychiatric Inventory (with anti-dementia drugs: MD = -3.23, 95% CI: -4.06 to -2.40). Adverse events were significantly less frequent in the HM group (RR = 0.50; 95% CI: 0.28 to 0.88). However, the methodological quality of the RCTs included in this systematic review was not optimal overall. Conclusion: According to the findings of this review, HM may be associated with additional benefits in BPSD treatment, particularly when used as an adjunct to conventional medications, including psychotropic and anti-dementia drugs. However, considering the methodological quality of the included RCTs, this clinical evidence is not robust. Nevertheless, dementia is a global health concern, and considering the limitations of conventional psychotropic drugs for BPSD, a major cause of the disease burden, HM appears to be a promising complementary therapy that warrants further research.

Project description:Background: Identifying the characteristics of behavioral and psychological symptoms of dementia (BPSD) associated with different dementia types may be a promising strategy to effectively deal with BPSD. We aimed to synthesize the prevalence rates of BPSD characteristics in community-dwelling dementia patients. Methods: We searched Medline, EMBASE, and PsycARTICLES databases for original clinical studies published until December 2020 that enrolled at least 300 community-dwelling dementia patients. The methodological qualities of prevalence studies were assessed using the Joanna Briggs Institute's critical appraisal checklist. Results: Thirty studies were included. The prevalence of the BPSD characteristic ranged from 4 (elation and mania) to 32% (apathy) in the pooled samples. The prevalence of delusions, anxiety, apathy, irritability, elation and mania, and aberrant motor behavior in Alzheimer's disease patients was 1.72-2.88 times greater than that in vascular dementia (VD) patients, while the prevalence of disinhibition in VD patients was 1.38 times greater. The prevalence of anxiety, irritability, and agitation and aggression, delusion, hallucinations, apathy, disinhibition, and aberrant motor behavior tended to increase as the severity of dementia increased, while that of depression, eating disorder, sleep disorders, and elation and mania tended to stable. In community-dwelling patients with dementia, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was higher than 20%, while that of disinhibition and elation and mania was lower than 10%. Conclusion: Overall, the pooled prevalence of apathy, depression, anxiety, irritability, agitation and aggression, sleep disorders, and eating disorder was generally high in patients with dementia. Also, the prevalence of some BPSD characteristics differed according to the type and the severity of dementia. The methodological quality of the included studies is not the best, and high heterogeneity may affect the certainty of the findings. However, the results of this review can deepen our understanding of the prevalence of BPSD. Systematic Review Registration: https://osf.io/dmj7k, identifier: 10.17605/OSF.IO/DMJ7K.

Dataset Information

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

Publications

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

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