Impact of Transcranial Direct Current Stimulation-Induced Electric Fields on Slowing Cognitive Decline in Older Adults With Mild Cognitive Impairment or Remitted Major Depressive Disorder: An Analysis of the PACt-MD Randomized Clinical Trial.

BACKGROUND

Mild cognitive impairment and remitted major depressive disorder increase the risk of dementia. The PACt-MD (Prevention of Alzheimer's Dementia With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) trial (NCT02386670) has shown that combined cognitive remediation (CR) and transcranial direct current stimulation (tDCS) improve cognitive outcomes by targeting executive function and presumably leveraging neurophysiological mechanisms. Our study investigated whether the magnitude of electric fields (EFs) induced by tDCS in the dorsolateral prefrontal cortex (DLPFC) predicted cognitive response in PACt-MD participants.

METHODS

Data from the 143 PACt-MD participants (mean [SD] age = 71.8 [6.34] years) who received active CR+tDCS and had brain magnetic resonance imaging (MRI) were analyzed. EFs were estimated using individual MRI with tDCS electrode placement at Fz (anode) and Iz (cathode). Participants were split into high- and low-EF groups based on the median. We used linear mixed models to assess the effect of EF in the left and right DLPFC on global cognitive decline, the primary outcome of PACt-MD, over 72 months. The global cognitive decline is the average of z scores on all tests on the neuropsychological battery.

RESULTS

EF magnitude in the left DLPFC was associated with global cognitive decline (likelihood ratio test: p = .026). Participants with high EF showed slower cognitive decline than those with low EF, irrespective of diagnosis and APOE ε4 status. No significant association was observed for the right DLPFC.

CONCLUSIONS

Our findings support that high EF in the DLPFC is associated with the efficacy of CR+tDCS. In future studies, tDCS dosing that results in a higher EF in the left DLPFC may improve the cognitive outcomes of CR+tDCS.