High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer’s Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position

Abstract

Background: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer’s disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. Objective: To measure the effect of individualized HD-tDCS in AD patients. Methods: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient’s brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. Results: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. Conclusion: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Transcranial Direct Current Stimulation (tDCS) as a Useful Rehabilitation Strategy to Improve Cognition in Patients With Alzheimer's Disease and Parkinson's Disease: An Updated Systematic Review of Randomized Controlled Trials

“…The optimization of tDCS protocols should also start from early response of the patient to the treatment. Future tDCS studies would also take advantage of computational models to ensure a calibration of the stimulation technique on specificity of the patient ( 90 ). Finally, tDCS should be widely delivered to patients with neurological disorders as an at-home rehabilitation strategy under supervision of therapists, in order to improve personalized medicine purposes [cf.…”

Review of individualized current flow modeling studies for transcranial electrical stimulation

“…Stronger EFs were induced in target S1 and control areas in the young adults. However, no relationship between EF strength and performance change was foundRasmussen et al (2021). optimal for individual patients in terms of the electric field distribution in the brain.The active HD-tDCS group improved significantly in delayed memory and Mini Mental Status Examination performance compared to the sham group.Associations between the delayed memory effect of HD-tDCS and both E-field and cortical thickness were observed…”

“…Thus, the authors suggested simulating the stimulation intensity necessary to achieve an effective cortical electric field strength (Caulfield et al, 2022). An individual selection of the stimulation montage targeting the DLPFC with 4 × 1 montages relied on current flow modeling in individual head models from Alzheimer's disease patients (Rasmussen et al, 2021). In this study, the selection of the stimulation electrode configuration was based on the prediction of the highest anodal electric field strength in the left DLPFC.…”

Exploring the Frontiers of Neuroimaging: A Review of Recent Advances in Understanding Brain Functioning and Disorders

“…Some studies have reported improvements in cognitive function, memory, and daily living activities following TES with AD [125,126]. Studies using tDCS have reported improved cognitive function and memory in individuals with AD [127][128][129][130]. The following is a summary in Table 3.…”