Effect of Sodium Benzoate on Cognitive Function Among Patients With Behavioral and Psychological Symptoms of Dementia: Secondary Analysis of a Randomized Clinical Trial.

Abstract

Importance:

Female 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.

Objective:

To examine the potential gender difference in the effects of benzoate treatment on the behavioral and psychological symptoms of dementia (BPSD).

Design, Setting, and Participants:

This 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.

Interventions:

Six weeks of treatment of 250 to 1500 mg/d of sodium benzoate or placebo.

Main Outcomes and Measures:

The primary outcome measures were Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) and Behavioral Pathology in Alzheimer Disease Rating Scale (BEHAVE-AD) scores.

Results:

Among 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 Relevance:

These 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 Registration:

ClinicalTrials.gov Identifier: NCT02103673.

• Authors: Chieh-Hsin Lin, Ping-Kun Chen, Shi-Heng Wang, Hsien-Yuan Lane
• Journal: JAMA network open (JAMA Netw Open) Vol. 4 Issue 4 Pg. e216156 (04 01 2021) ISSN: 2574-3805 [Electronic] United States
• PMID: 33881530 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium Benzoate

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (drug therapy)
• Cognition (drug effects)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Male
• Sex Factors
• Sodium Benzoate (administration & dosage)