The role of transcranial direct current stimulation in improving learning and memory performances of patients with mild cognitive impairment and mild Alzheimer’s disease: a functional magnetic resonance imaging study

Abstract Background Transcranial direct current stimulation (tDCS) is a safe non‐invasive brain stimulation (NIBS) procedure which helps to stimulate a particular region of interest by modulating the neuronal firing rate, thereby modulating the cognitive functioning. The tDCS intervention is known to show improvement on memory recall and recognition in patients with mild cognitive impairment (MCI) and mild Alzheimer’s Disease (mild AD) Method We investigated the effect of anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation at the right supra‐orbital area in patients with MCI (n = 18) and mild AD (n = 20) (Refer Table 1), after due approval from Institute Ethics Committee NIMHANS. Both baseline and post‐intervention assessments for a single patient were administered by the different assessors allocated randomly using NIMHANS neuropsychological battery for elderly (NNB‐E). Two resting state functional magnetic resonance imaging (rsfMRI) acquisitions, before and after the ten sessions of tDCS, each session lasting 20 minutes. A spherical mask of 5 mm diameter was chosen a priori on the left middle frontal gyrus (LMFG) as a seed for performing seed based functional connectivity (sbFC) analysis using default preprocessing pipeline and pre‐post analysis setup in CONN 18b toolbox. Result The combined sample of patients with MCI and mild AD showed significant improvement in word list learning trial 3 (pre tDCS 5.85 (1.59); post tDCS 6.63 (1.67); Z = 3.586, p<0.0001) and delayed recall (pre tDCS 1.50 (1.88); post tDCS 2.45 (2.33); Z = 3.656, p<0.0001) scores using NNB‐E. The sbFC analysis showed significantly reduced functional connectivity between left MFG (the region of anodal stimulation) and posterior cingulate cortex (PCC) as well as precuneus cortex (cluster‐level extent threshold p‐FDR <0.05) after tDCS. Post‐hoc tests showed that these reductions after tDCS intervention were also found to be significantly associated with attention and auditory verbal learning memory scores (Refer Figure 1 and Table 2). Conclusion The tDCS intervention helped reducing the functional connectivity at rest, which was responsible for compensatory neuronal processes found in early AD. These findings unravel the therapeutic role of tDCS by enhancing auditory verbal memory performance and altering the functional connectivity at PCC and precuneus cortex in earlier stages of AD.