The Impact of Transcranial Direct Stimulation Therapy Combined with Intranasal Near-Infrared Stimulation on Cognitive Performance in Patients with Mild Cognitive Impairment and Alzheimer’s Disease: A Pilot Randomized, Double-Blind, Placebo-Controlled

INTRODUCTION: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are progressive neurodegenerative conditions with limited therapeutic options. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) and photobiomodulation (PBM) have shown promise in improving cognitive function, but their combined effects remain underexplored. METHODS: In a pilot randomized, double-blind, placebo-controlled trial, 33 participants were assigned to either active or sham stimulation groups. The intervention consisted of 50 sessions over 10 weeks, with tDCS (2 mA, F3-F4 montage) and intranasal near-infrared stimulation (iNIRS) (850 nm, 40 Hz, 50% duty cycle) administered simultaneously. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and ADAS-Cog at baseline, post-treatment, and at the 12-week follow-up. RESULTS: Significant improvements were observed in the active group across both scales. MMSE scores increased from 21.89 ± 2.35 to 27.22 ± 1.96 (p = 0.0001), with sustained effects at follow-up. ADAS-Cog scores decreased from 34.78 ± 4.99 to 18.22 ± 4.4 (p < 0.0001). Post hoc analyses revealed significant changes in attention, recall, praxis, and executive domains. No serious adverse events were reported. CONCLUSION: Combined tDCS and iNIRS therapy significantly enhances cognitive performance in patients with MCI and mild AD. This synergistic, non-invasive approach may offer a promising therapeutic strategy to delay cognitive decline and reduce care-related burdens. TRIAL REGISTRATION: ClinicalTrials.gov NCT07290686; Registration date 14 December 2023.