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

J Alzheimers Dis. 2015;48(1):251-60. doi: 10.3233/JAD-150067.


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.

Keywords: Alzheimer’s disease; brain atrophy; cognitive functions; noninvasive brain stimulation; source-based morphometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Analysis of Variance
  • Cerebral Cortex / physiology*
  • Cognition Disorders* / etiology
  • Cognition Disorders* / pathology
  • Cognition Disorders* / therapy
  • Female
  • Gray Matter / pathology
  • Gray Matter / physiopathology*
  • Humans
  • Male
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Transcranial Magnetic Stimulation / methods*
  • Treatment Outcome