Abstract
BACKGROUND: Studies have shown the clinical effects of repetitive transcranial magnetic stimulation (rTMS) on depression in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. The measurement of brain activation links neurobiological and functional aspects but is challenging in patients with dementia. This study investigated the influence of rTMS on cortical activation in patients with AD and depressive symptoms, measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task. METHODS: In this randomized, double-blind study, patients with AD and depression received either active rTMS (n = 17) or sham-rTMS (n = 16). Patients received 4 weeks of bilateral standard rTMS (1 Hz rTMS delivered to the right dorsolateral prefrontal cortex (DLPFC) and 10-Hz rTMS delivered to the left DLPFC). RESULTS: No significant changes were found in the Mini-Mental State Examination (MMSE) and Modified Barthel Index (MBI); however, significant changes were found for the 17-item Hamilton Depression Rating Scale (HAMD-17) and the depression score of the Neuropsychiatric Inventory (NPI-depression; p < 0.05). The results showed a decrease in the concentration of oxygenated hemoglobin, as measured with fNIRS, from baseline to week 4 in CH41 (in right DLPFC; p = 0.0047, FDR-corrected). There was a negative correlation between the improvement in HAMD-17 severity in these patients and reduced oxygenated hemodynamic response of CH41 (r = - 0.504, p = 0.039). CONCLUSION: The results indicated a positive effect of rTMS on depression in patients with AD. The underlying cortical changes were imaged using fNIRS. Prefrontal activation measured by fNIRS is a potential biomarker for monitoring the response of patients with depression in AD to rTMS treatment.