Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges

Abstract

Alzheimer’s disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients’ and families’ quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.

Brain Waste Removal System and Sleep: Photobiomodulation as an Innovative Strategy for Night Therapy of Brain Diseases

“…The purpose of our review is to highlight non-pharmacological strategies for the stimulation of the BWRS that have a high potential to be introduced into routine clinical practice, as well as those that can become smart sleep gadgets used at home and while traveling without reducing the high pace of life of modern people. In this aspect, photonic technologies are the most promising, since they are already widely used in the clinical field for the treatment of various brain diseases [ 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ]. tPBM of the BWRS is the only non-pharmacological technology proposed to activate the lymphatic excretion of metabolites and toxins from brain tissues [ 9 , 28 , 82 , 83 , 111 , 112 , 113 , 114 , 115 , 129 ].…”

“…Recent reviews highlight the actual applications of tPBM to the therapy of sleep disorders [ 9 , 116 ] and brain diseases associated with sleep injuries, including AD [ 117 , 118 , 119 , 120 ], psychological problems [ 121 ], brain trauma [ 122 ] and other neurological diseases [ 123 , 124 ]. tPBM, known as low-level light therapy, is a technique of non-invasive treatment with red and near-infrared light irradiation in a photo-therapeutic window (between 600 and 1300 nm) [ 125 , 126 ].…”

Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review

“…Furthermore, strength training exercise improves higher-level cognitive processes and memory, stabilizes brain volume, and decreases white matter lesions. Mind-body exercise combined with body movement improves balance, coordination, gait, and agility; improves neuronal, synaptic, and vascular systems of the brain; promotes the connectivity of brain regions, thereby improving executive function, memory, and emotional status; and curbs neuronal inflammation, all of which improve brain health [ 26 , 27 , 37 , 61 , 62 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. …”

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

“…A synthesis of molecular and cellular mechanisms resulting from PBM action on living cells, in neurodegenerative diseases, as well as recent advances and challenges in AD have been presented in various reviews [ 241 , 257 , 259 , 279 , 280 ].…”