Application of Repetitive Transcranial Magnetic Stimulation over the Dorsolateral Prefrontal Cortex in Alzheimer’s Disease: A Pilot Study

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is reportedly a potential tool to understand the neural network; however, the pathophysiological mechanisms underlying cognitive function change remain unclear. This study aimed to explore the cognitive function changes by rTMS over the bilateral dorsolateral prefrontal cortex (DLPFC) in Alzheimer’s disease (AD). We evaluated the feasibility of rTMS application for mild cognitive dysfunction in patients with AD in an open-label trial (UMIN000027013). An rTMS session involved 15 trains at 120% resting motor threshold on each side (40 pulses/train at 10 Hz). Efficacy outcome measures were changes from baseline in cognitive function, assessed based on the AD Assessment Scale-cognitive subscale, Mini-Mental State Examination, Japanese version of Montreal Cognitive Assessment (MoCA-J), Behavioral and Psychological Symptom of Dementia, and Instrumental Activity of Daily Living scores. Sixteen patients with AD underwent five daily sessions of high-frequency rTMS over the bilateral DLPFC for 2 weeks. All participants completed the study; no major adverse effects were recorded. The MoCA-J score increased by 1.4 points (±0.15%) following 2 weeks of stimulation. At 1 month following rTMS cessation, all cognitive functional scores returned to the original state. Our findings suggest that the DLPFC plays an important role in the neural network in AD.