Phototherapy of Alzheimer’s Disease: Photostimulation of Brain Lymphatics during Sleep: A Systematic Review

Abstract

The global number of people with Alzheimer’s disease (AD) doubles every 5 years. It has been established that unless an effective treatment for AD is found, the incidence of AD will triple by 2060. However, pharmacological therapies for AD have failed to show effectiveness and safety. Therefore, the search for alternative methods for treating AD is an urgent problem in medicine. The lymphatic drainage and removal system of the brain (LDRSB) plays an important role in resistance to the progression of AD. The development of methods for augmentation of the LDRSB functions may contribute to progress in AD therapy. Photobiomodulation (PBM) is considered to be a non-pharmacological and safe approach for AD therapy. Here, we highlight the most recent and relevant studies of PBM for AD. We focus on emerging evidence that indicates the potential benefits of PBM during sleep for modulation of natural activation of the LDRSB at nighttime, providing effective removal of metabolites, including amyloid-β, from the brain, leading to reduced progression of AD. Our review creates a new niche in the therapy of brain diseases during sleep and sheds light on the development of smart sleep technologies for neurodegenerative diseases.

Technology of the photobiostimulation of the brain’s drainage system during sleep for improvement of learning and memory in male mice

“…Typically, in experimental and clinical studies, PBM is performed in awake subjects [ 15 , 30 – 38 ]. In our recent review, we suggested that there are no commercial devices for simultaneous PBM and sleep monitoring, which significantly limits the clinical investigations the therapeutic effects of PBM during sleep [ 16 ].…”

“…In our recent review, we suggested that there are no commercial devices for simultaneous PBM and sleep monitoring, which significantly limits the clinical investigations the therapeutic effects of PBM during sleep [ 16 ]. We discussed that the development of sleep-PBM technologies is urgently needed and could become a breakthrough step in the progress of AD therapy in humans [ 15 , 16 ]. The technology proposed in this study opens new perspectives of development of promising PBM devices for night phototherapy of brain diseases and its implementation in clinical practice.…”

“…Despite the fact that the meninges do not belong to brain tissues, the role of meningeal lymphatic vessels (MLVs) in the removal of metabolites and toxins from brain tissues has been shown in many works [ 8 – 14 ]. Currently, MLVs is considered as a main part of brain’s drainage system (BDS) [ 3 , 15 , 16 ]. It is now known that dysfunction of MLVs plays an important role in the development of a large number of brain diseases, including Alzheimer’s (AD) [ 8 , 9 , 13 , 14 ] and Parkinson’s diseases [ 17 ], brain trauma [ 12 ] and tumors [ 18 – 20 ], intracranial hemorrhages [ 10 , 11 ].…”

“…It is believed that only deep sleep or delta activity of the brain is accompanied by intense clearance of wastes, metabolites and toxins from the brain [ 43 ]. There is hypothesis that during deep sleep, the size of PVSs and the volume of interstitial fluids increase, promoting the removal of metabolites from brain tissue [ 15 , 16 , 43 ]. During wakefulness, the size of PVSs decreases and the exchange between fluids and brain tissue is suppressed.…”

“…Based on these new data, the idea of using PBM during deep sleep has been proposed as a promising new direction in the improvement of cognitive performance, executive functions, attention and memory [ 15 , 16 , 45 – 47 ]. However, PBM is typically used in the awake state [ 15 , 30 – 38 ]. There are no technologies for PBM during sleep [ 16 ].…”