The Efficacy and Safety of Transcranial Photobiomodulation for Mild Cognitive Impairment Due to Alzheimer’s Disease: A Randomized, Double-Blind, Sham-Controlled Study

<b><i>Background:</i></b> Transcranial photobiomodulation (tPBM) is a promising noninvasive neuromodulation modality with potential therapeutic benefits for neurodegenerative diseases. Infrared light delivered by a tPBM device penetrates the cortex, stimulating neuronal activity by increasing mitochondrial adenosine triphosphate production and enhancing regional cerebral blood flow. <b><i>Objective:</i></b> This study investigated the efficacy and safety of a self-administered, at-home, wearable tPBM device for improving cognitive function in individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). <b><i>Methods:</i></b> Individuals with MCI due to AD, diagnosed according to the National Institute on Aging and Alzheimer's Association criteria, with a Korean version of Mini-Mental State Examination-2 (K-MMSE2) score of 23-27 and a global Clinical Dementia Rating (CDR) score of 0.5-1.0 were enrolled. Subjects self-administered tPBM six times per week for 12 weeks. Assessments were conducted at weeks 7 and 13 using the Korean version of the Montreal Cognitive Assessment (K-MoCA), K-MMSE2, the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease, and the Geriatric Depression Scale. <b><i>Results:</i></b> A total of 26 participants were enrolled. The treatment group showed a statistically significant improvement in K-MoCA scores at week 13 (<i>p</i> < 0.05) compared with the sham group. Although K-MMSE2 scores improved in the treatment group, the difference was not statistically significant. No serious adverse events were reported. <b><i>Conclusion:</i></b> Findings suggest that tPBM is an effective and safe home-use intervention for individuals with MCI, with promising therapeutic and preventative roles in Alzheimer's dementia.