Benzoate treatment may improve cognitive function for women with later-phase dementia

Benzoate treatment appeared to improve cognitive function among women with later-phase dementia, according to results of a secondary analysis of a randomized clinical trial published in JAMA Network Open.

“In an earlier randomized, double-masked, placebo-controlled trial, sodium benzoate, a pivotal [D-amino acids oxidase] inhibitor, significantly improved the cognitive function of patients with early-phase [Alzheimer’s disease] (without behavioral and psychological symptoms of dementia), with a mean dose of 716.7 mg/d at week 24,” Chieh-Hsin Lin, MD, PhD, of the department of psychiatry at Kaohsiung Chang Gung Memorial Hospital in Taiwan, and colleagues wrote. “On the other hand, in a 2019 randomized, double-blind, placebo-controlled trial on dementia with behavioral and psychological symptoms, benzoate did not surpass placebo in restoring cognitive function or reducing behavioral and psychological symptoms, while benzoate and placebo showed a similar safety profile.”

Lin and colleagues aimed to assess the possible gender difference in the effects of benzoate treatment on dementia-related behavioral and psychological symptoms. They analyzed data of 97 patients (64% women; mean age, 75.4 years) with behavioral and psychological symptoms who were included in a randomized, double-masked, placebo-controlled trial that took place across three major medical centers in Taiwan. Participants received 6 weeks of treatment with 250 mg to 1,500 mg per day of sodium benzoate (n = 49) or placebo (n = 48). Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) and Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) scores served as primary outcome measures.

Results showed 6 weeks of treatment with benzoate was associated with significantly greater performance on the ADAS-cog but not BEHAVE-AD among 62 women. ADAS-cog and BEHAVE-AD scores were not significantly different between the two treatment groups among 35 men. Benzoate treatment compared with placebo increased women’s estradiol to follicle-stimulating hormone ratios.

“Diverse manifestations and courses of dementia may represent numerous pathogeneses,” Lin and colleagues wrote. “Whether sodium benzoate can help at least a portion of dementia patients, such as women or patients at a younger age and earlier phase of illness, deserves more studies with longer duration and higher doses (and perhaps also lower doses) for confirmation.”