Distinct Pattern of Gray Matter Atrophy in Mild Alzheimer's Disease Impacts on Cognitive Outcomes of Noninvasive Brain Stimulation.

BACKGROUND

Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to study and modulate brain plasticity.

OBJECTIVE

Our aim was to investigate the effects of rTMS on cognitive functions in patients with mild cognitive impairment and Alzheimer's disease (MCI/AD) and assess the effect of gray matter (GM) atrophy on stimulation outcomes.

METHODS

Twenty MCI/AD patients participated in the proof-of-concept controlled study. Each patient received three sessions of 10 Hz rTMS of the right inferior frontal gyrus (IFG), the right superior temporal gyrus (STG), and the vertex (VTX, a control stimulation site) in a randomized order. Cognitive functions were tested prior to and immediately after each session. The GM volumetric data of patients were: 1) compared to healthy controls (HC) using source-based morphometry; 2) correlated with rTMS-induced cognitive improvement.

RESULTS

The effect of the stimulated site on the difference in cognitive scores was statistically significant for the Word part of the Stroop test (ST-W, p = 0.012, linear mixed models). As compared to the VTX stimulation, patients significantly improved after both IFG and STG stimulation in this cognitive measure. MCI/AD patients had significant GM atrophy in characteristic brain regions as compared to HC (p = 0.029, Bonferroni corrected). The amount of atrophy correlated with the change in ST-W scores after rTMS of the STG.

CONCLUSION

rTMS enhanced cognitive functions in MCI/AD patients. We demonstrated for the first time that distinct pattern of GM atrophy in MCI/AD diminishes the cognitive effects induced by rTMS of the temporal neocortex.