A Pilot Double-Blind Randomized Controlled Trial of Cognitive Training Combined with Transcranial Direct Current Stimulation for Amnestic Mild Cognitive Impairment.

Background: There is currently no effective intervention for improving memory in people at increased risk for dementia. Cognitive training (CT) has been promising, though effects are modest, particularly at follow-up. Objective: To investigate whether adjunctive non-invasive brain stimulation (transcranial direct current stimulation, tDCS) could enhance the memory benefits of CT in amnestic mild cognitive impairment (aMCI). Methods: Participants with aMCI were randomized to receive CT with either Active tDCS (2 mA for 30 min and 0.016 mA for 30 min) or Sham tDCS (0.016 mA for 60 min) for 15 sessions over a period of 5 weeks in a double-blind, sham-controlled, parallel group clinical trial. The primary outcome measure was the California Verbal Learning Task 2nd Edition. Results: 68 participants commenced the intervention. Intention-to-treat (ITT) analysis showed that the CT+Active tDCS group significantly improved at post treatment (p = 0.033), and the CT+Sham tDCS group did not (p = 0.050), but there was no difference between groups. At the 3-month follow-up, both groups showed large-sized memory improvements compared to pre-treatment (CT+Active tDCS: p < 0.01, d = 0.99; CT+Sham tDCS: p < 0.01, d = 0.74), although there was no significant difference between groups. Conclusion: This study found that CT+Active tDCS did not produce greater memory improvement compared to CT+Sham tDCS. Large-sized memory improvements occurred in both conditions at follow-up. One possible interpretation, based on recent novel findings, is that low intensity tDCS (used as 'sham') may have contributed biological effects. Further work should use a completely inert tDCS sham condition.