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Personalized repetitive transcranial magnetic stimulation (rTMS) targeting the hippocampal network improved cognitive and functional performance in patients with early Alzheimer's disease (AD), new research showed.

The improvements were evident 4 and 8 weeks after treatment and correlated with increased functional connectivity in the hippocampal-cortical network.

"The positive results of our study suggest that rTMS could be considered an add-on treatment for AD," lead investigator Young Hee Jung, MD, PhD, Department of Neurology, Myongji Hospital, Hanyang University, Goyang, Korea, and colleagues wrote. 

The study was published online on May 6 in JAMA Network Open. 

Promising Nondrug Add-on?

rTMS has emerged as a promising intervention for AD, but choice of stimulation site is key to the therapy's efficacy. 

For their study, Jung and colleagues employed personalized functional MRI (fMRI) connectivity analysis to guide hippocampal network-targeted stimulation coupled with a personalized 3D-printed frame to secure the coil to the optimal target site. 

They randomly allocated 41 adults with early AD and evidence of an amyloid biomarker to personalized rTMS or sham stimulation (20 sessions over 4 weeks), with assessments conducted at 4 and 8 weeks.

Thirty participants (mean age, 70 years; 60% women) completed the 8-week trial: 18 in the active rTMS group and 12 in the sham group.

Compared with the sham group, the rTMS group showed significant improvement in the AD Assessment Scale-Cognitive Subscale (ADAS-Cog), particularly in the memory domain, at 8 weeks (primary outcome: P = .002). The between-group difference in improvement on the ADAS-Cog was also significant at 4 weeks (P = .007).

The rTMS group also showed a larger improvement on the Clinical Dementia Rating-Sum of Boxes scale than did the sham group at 4 weeks (P = .05) and 8 weeks (P = .008) and the Seoul-Instrumental Activity Daily Living scale at 8 weeks (P = .002); thus, there were two secondary outcomes. 

The fMRI connectivity analysis showed that rTMS increased functional connectivity between the hippocampus and precuneus, which correlated with improvements in the ADAS-Cog (P =.005). 

"As a core region in the default mode network (DMN), the precuneus is critically involved in episodic memory retrieval. Its abnormal activity with reduced functional connectivity is considered a biomarker of early AD," the study team wrote. 

"Thus, our neuroimaging results aligning with the critical role of the precuneus are noteworthy because the measurable changes in the precuneus supported the improvement in clinical scores. These changes could serve as a biomarker for treatment effectiveness, further strengthening the credibility of our network-targeting rTMS approach to modulate the hippocampal-cortical memory network," they added. 

Taken together, the researchers say their results "support the consideration of rTMS as a potential nonpharmacological treatment for AD."

Funding for the study was provided in part by Remed Co Ltd. Three authors report they have a patent pending for the design and production of personalized masks.