Predictors of efficacy, tolerability and discontinuation of Transcranial Direct Current Stimulation (tDCS) for Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD): a meta-analysis and meta-regression

Numerous patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) are refractory to pharmacological treatment, and non-invasive brain neurostimulation has been investigated as another possibility for improving cognition. The performed meta-analysis and meta-regression verified predictors of efficacy, tolerability, and discontinuation of transcranial direct current stimulation (tDCS) for treating MCI or AD. The analyzed studies used the Mini-Mental State Exam, Montreal Cognitive Assessment, or Alzheimer's Disease Assessment Scale - Cognitive Subscale scores as outcome measures. Databases (PubMed, Embase, and Web of Science - primary collection) were searched, resulting in 12 published randomized and controlled trials. The risk of bias assessment was based on Cochrane Review recommendations, considering study characteristics. Other evaluated outcomes were the number of adverse effects (tolerability) and dropouts. Overall and anodal tDCS improved cognition compared to the sham protocol. Group comparisons did not show statistically significant differences for adverse effects and dropouts. Session duration was a response predictor, as stimulations of up to 20 minutes for ten days or more improved the outcome achievement. The AD diagnosis covariate also affected efficacy. The findings should be interpreted carefully in clinical practice because the stimulation effect may vary among subjects.