Randomised–controlled trial of transcranial direct current stimulation as augmentation to cognitive training in Alzheimer's disease

Background

To explore the potential synergistic effect of tDCS with cognitive training, efficacy of 2-week (5 sessions per week) tDCS to augment cognitive training in subjects with mild Alzheimer’s disease was investigated. The primary objective of the study was to investigate whether tDCS can enhance the cognitive training effect as an augmentation therapy. The hypotheses were (1) Adaptive n-back task training with either active or sham tDCS can enhance cognitive function; (2) Active tDCS is significantly more effective than sham tDCS as an augmentation to cognitive training in enhancing cognitive function; (3) Adaptive n-back task training with either active or sham tDCS has sustained effect after intervention.

Methods

The trial was conducted as a parallel, double-blinded, sham-controlled randomized study in Hong Kong. Recruited Chinese ≥ 65y/o, right-handed, diagnosed to have major neurocognitive disorders due to Alzheimer’s disease with clinically mild severity, as defined by DSM-5 and with Global Clinical Dementia Rating= 1. They were randomly assigned to receive either 2-week (5 sessions per week) active or sham tDCS in 1:1 ratio simultaneously with cognitive training by an adaptive n-back task using a computerized program. The participants were assessed at baseline (T0), after intervention (T1) and 4 weeks after the course of intervention (T2) for the primary outcome (Adaptive N-back Performance and Digit Span) and secondary outcome (Trail Making Test, CDR-SOB, CNPI total and CNPI caregiver distress scale). Participants and assessor were blinded from the group allocation.

Statistical method

Descriptive analysis was peformed to assessed for any groups difference at baseline. Homogeneity at baseline between the groups were compared. Two-way ANOVA was performed to examine the differences between the two groups on other variables across all time points. GLMM was used to evaluate the accuracy of N-back hit rates across different difficulty levels.

Results

Among participants recruited, 20 were assigned to active and 21 were assigned to sham. No participants dropped out. No major adverse effects were reported.

In primary outcomes, significant time effects were found in adaptive n-back reaction time (p=0.024), adaptive n-back true correct (n=1: p=0.027; n=2: p<0.001), forward digit span (p<0.001), backward digit span (p<0.001). In secondary outcome, significant time effect was found in both Trail Making Test Part A (p<0.001), Trail Making Test Part B (p=0.020) and CDR-SOB (p=0.008). The improvement of the outcomes above was sustained 4 weeks after intervention. Both CNPI total and CNPI caregiver distress scale showed no time effect. There were no group differences nor group-time effects found in both primary and secondary outcomes between active and sham group.

Conclusions

2-week cognitive training by adaptive n-back task combined with either active or sham tDCS improved cognitive function in terms of attention, working memory and dementia severity in mild Alzheimer’s disease, lasting 4 weeks after the intervention, but was not reflected in neuropsychiatric rating. There was insufficient evidence on the near transfer effect to other cognitive abilities. There was no significant additional effect of active tDCS compared to sham tDCS as an augmentation on cognitive training. Overall, tDCS was well tolerated in the trial.

References

No references