Benzoate treatment beneficial in women with late stage dementia;JAMA

"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."the research team opined.

Female gender is a major risk factor for dementia; however, gender has not yet been adequately addressed by clinical trials. A recent study has demonstrated that sodium benzoate, a D-amino acid oxidase inhibitor, improved cognitive function in early-phase Alzheimer disease.

To gain deeper understanding on this, the team undertook the current study to examine the potential gender difference in the effects of benzoate treatment on the behavioral and psychological symptoms of dementia (BPSD).

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. Six weeks of treatment of 250 to 1500 mg/d of sodium benzoate or placebo. The primary outcome measures were Alzheimer disease assessment scale–cognitive subscale (ADAS-cog) and Behavioral Pathology in Alzheimer Disease Rating Scale (BEHAVE-AD) scores.

Data analysis revealed some interesting facts.

• 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).

"When considering the results of this post hoc secondary analysis of a randomized clinical trial on later-phase dementia with behavioral and psychological symptoms alongside our previous clinical trial on early-phase dementia, sodium benzoate, an indirect NMDAR agonist, can improve the cognitive function of all patients with early-phase dementia, but only benefit the cognitive function of female patients with later-phase dementia and behavioral and psychological symptoms. More studies are warranted to elucidate the underlying mechanisms." the team concluded.

Primary source: JAMA Network Open

For the full article follow the link: doi:10.1001/jamanetworkopen.2021.6156