Effect and potential mechanism of photobiomodulation therapy on cognitive deficits in animal models of Alzheimer's disease: a systematic review and meta-analysis.

Abstract

Background: As a progressive neurodegenerative disorder, Alzheimer's disease (AD) has limited effective therapeutic options. Photobiomodulation (PBM) therapy, a non-invasive light therapy, represents a potential strategy for neurological diseases; however, its preclinical findings have been inconsistent. While previous reviews have summarized PBM's potential, this study is the first quantitative meta-analysis synthesizing preclinical evidence of PBM therapy in AD animal models, evaluating its effects on cognitive and neuropathological outcomes.

Methods: We performed a systematic search across seven electronic databases to identify all relevant studies. A meta-analysis of 16 eligible studies evaluated the effects of PBM on cognitive outcomes and key neuropathological markers. Subgroup analyses were stratified by animal model and interventions (wavelength, energy density).

Results: From 16 eligible studies, the meta-analysis found that PBM therapy significantly improved cognitive function (e.g., learning ability: MD =  - 7.18; 95% CI  - 9.87 to - 4.48), based on data from 386 animals. However, this was associated with significant heterogeneity (I² = 88%, p < 0.00001). PBM also significantly reduced Aβ deposition (SMD =  - 0.96; I² = 55%) and p-Tau levels (SMD =  - 2.24; I² = 14%). From a mechanistic standpoint, the activity of cytochrome c oxidase (CCO) is enhanced by PBM therapy. Subgroup analysis by animal model showed that PBM therapy was associated with greater improvement of learning and memory ability in transgenic animals. In different wavelengths, PBM using wavelengths greater than 750 nm showed numerically greater effects on learning ability. In different energy densities, PBM with an energy density less than or equal to 3 J/cm² was associated with greater improvement in learning ability and memory ability.

Conclusions: This meta-analysis demonstrates that PBM has significant therapeutic potential for AD animal models by improving cognition and ameliorating key pathologies. The mechanisms likely involve mitigating oxidative stress and enhancing mitochondrial function. While preclinical evidence strongly supports the efficacy of PBM, translation to humans requires careful optimization of treatment parameters and dose-response relationships. Further high-quality preclinical trials are crucial to validate the therapeutic potential of PBM for AD.