Long-lasting improvements in episodic memory among subjects with mild cognitive impairment who received transcranial direct current stimulation combined with cognitive treatment and telerehabilitation: a multicentre, randomized, active-controlled study

Abstract

Background: In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI).

Objective: The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU).

Results: An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU.Moreover, the combined treatment led to prolonged beneficial effects (clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06).

Discussion: The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation.

Clinical trial registration: https://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1, NCT03486704.

Keywords: MCI; cognition; tDCS; telerehabilitation; transcranial direct current stimulation.

Figure 1

Flow chart showing study subject enrolment and sample processing.

Figure 2

Experimental procedure for the face-to-face cognitive virtual reality rehabilitation system combined with anodal tDCS followed by cognitive telerehabilitation (clinic-atDCS-VRRS+Tele@H-VRRS) and for face-to-face cognitive virtual reality rehabilitation system combined with placebo tDCS followed by cognitive telerehabilitation (clinic-ptDCS-VRRS+Tele@H-VRRS). (A) Face-to-face (FTF) cognitive virtual reality rehabilitation system (VRRS) combined with tDCS followed by cognitive telerehabilitation. (B) Timeline for the experimental protocol of the FTF cognitive virtual reality rehabilitation system (VRRS) combined with anodal or placebo tDCS followed by cognitive telerehabilitation. (C) Current flow model of tDCS montage (anode over F3 and cathode over the right supraorbital area), using two 7×5 cm sponge pads represented in axial, sagittal and coronal views from the Male 1 model in the Soterix HD Targets software (Soterix Medical). Arrows represent the direction of current flow.

Figure 3

(A) Effects of face-to-face (FTF) cognitive virtual reality rehabilitation system (VRRS) combined with anodal tDCS followed by cognitive telerehabilitation (clinic-atDCS-VRRS+Tele@H-VRRS) vs. FTF cognitive VRRS combined with placebo tDCS followed by cognitive telerehabilitation (clinic-ptDCS-VRRS+Tele@H-VRRS) vs. FTF cognitive treatment as usual (clinic-TAU) on the immediate free recall (IFR) score of the Free and Cued Selective Reminding Test (FCSRT). Asterisks indicate significant comparisons for clinic-atDCS-VRRS+Tele@H-VRRS from T0 to T1 (p < 0.001) and from T0 to T3 (p < 0.001). (B) Long-term beneficial effects of face-to-face VRRS during anodal tDCS followed by cognitive telerehabilitation (clinic-atDCS-VRRS+Tele@H-VRRS). Box-plot of the delta deviations (differences between the scores recorded at time T3 and those at baseline T0) for the different conditions are reported. Asterisks indicate conditions that differed significantly from those of the clinic-atDCS-VRRS+Tele@H-VRRS group.