Using photobiomodulation to alter the pathophysiology of Alzheimer’s disease:
Model, Evidence, and Future of EEG Guided Intervention
This manuscript outlines the model of the pathophysiology of Alzheimer’s disease (AD) in the progressive layers, from its origin to the development of biomarkers, and then to symptom expression. Genetic susceptibility is the main factor leading to mitochondrial dysfunction and subsequent accumulation of amyloid and tau proteins, which has been identified as a hallmark of AD. In addition to these accumulations, we also explored a wider range of pathophysiological aspects, including blood-brain barrier, blood flow, vascular health, gut brain microbiota data, lymphatic flow, metabolic syndrome, energy deficiency, oxidative stress, calcium overload, inflammation, neuronal and synaptic loss, brain matter atrophy, and reduced growth factors. Photobiomodulation (PBM) is introduced as a treatment method that uses portable devices to transmit near-infrared light to selected brain regions. PBM has the potential to address every aspect of pathophysiology, with data provided by various studies. They provide mechanistic support for most published small-scale clinical studies that demonstrate improvements in memory and cognition. They informed that PBM has the potential to treat AD and are waiting for validation in large randomized controlled trials. The presentation of brain network and waveform changes on electroencephalography (EEG) provides an opportunity to use this data as a guide for applying various PBM parameters to improve results. These parameters include wavelength, power density, treatment duration, LED positioning, and pulse frequency. It has been found that pulses of specific frequencies can affect the expression of waveforms and the modification of brain networks. As revealed by recent research, this expression originates from the regulation of cellular and protein structures. These findings provide EEG based guidelines for personalized AD treatment using artificial intelligence through EEG data feedback.
Introduce
Alzheimer’s disease (AD) is a major public health issue worldwide. For decades, people have explored treatment strategies, but have not yet developed curative treatment methods (1). Although the FDA has recently approved lecanemab (Leqembi) and donanemab (Kisunla) for the treatment of cognitive decline in early Alzheimer’s disease, their efficacy is moderate, with potential side effects such as amyloid associated imaging abnormalities (ARIA), and their long-term impact on disease progression remains uncertain, especially in late stages (2,3) However, these drugs represent significant progress by objectively reducing amyloid beta (A β) markers, which are said to slow down disease progression in early AD patients, marking an important first step towards more effective treatment.
The pathophysiology of AD is a complex and thoroughly researched field, ultimately without a clear solution. While continuing our research to find clear answers, we will review the pathophysiological aspects revealed in AD studies, synthesize relevant photobiomodulation (PBM) research results, demonstrate its ability to alter these aspects, and then evaluate PBM as a potential candidate therapy. Although these mechanisms constitute the majority of the discussion, we attach great importance to their impact on humans in clinical research, which will also examine the effects of various parameters of PBM. The reviewed clinical studies are provided in the form of peer-reviewed publications, with a deadline of January 31, 2024.