Adjunctive transcranial direct current stimulation (tDCS) plus sodium benzoate for the treatment of early-phase Alzheimer's disease: A randomized, double-blind, placebo-controlled trial

Previous studies found that an NMDA receptor (NMDAR) enhancer, sodium benzoate, improved cognitive function of patients with early-phase Alzheimer's disease (AD). Transcranial direct current stimulation (tDCS) induces NMDAR-dependent synaptic plasticity and strengthens cognitive function of AD patients. This study aimed to evaluate efficacy and safety of tDCS plus benzoate in early-phase dementia. In this 24-week randomized, double-blind, placebo-controlled trial, 97 patients with early-phase AD received 10-session tDCS during the first 2 weeks. They then took benzoate or placebo for 24 weeks. We assessed the patients using Alzheimer's disease assessment scale - cognitive subscale (ADAS-cog), Clinician's Interview-Based Impression of Change plus Caregiver Input, Mini Mental Status Examination, Alzheimer's disease Cooperative Study scale for ADL in MCI, and a battery of additional cognitive tests. Forty-seven patients received sodium benzoate, and the other 50 placebo. The two treatment groups didn't differ significantly in ADAS-cog or other measures. Addition of benzoate to tDCS didn't get extra benefit or side effect in this study. For more thoroughly studying the potential of combining tDCS with benzoate in the AD treatment, future research should use other study designs, such as longer-term benzoate treatment, adding benzoate in the middle of tDCS trial sessions, or administering benzoate then tDCS.