With the population aging rapidly, neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) have become major health concerns. According to the World Health Organization, over 55 million people worldwide live with dementia, with AD accounting for 60 - 70% of cases (WHO, 2023). Meanwhile, about 10 million people globally suffer from PD, and this number is expected to double by 2040 (Dorsey et al., 2018). Traditional treatments have limitations, but repetitive transcranial magnetic stimulation (rTMS) combined with phototherapy is emerging as a promising alternative. This article explores how rTMS and phototherapy could offer new hope for patients with AD and PD.
Understanding the Mechanisms of Alzheimer's and Parkinson's Diseases
Alzheimer's Disease
AD is characterized by the accumulation of abnormal proteins in the brain. The two main pathological hallmarks are beta-amyloid plaques and neurofibrillary tangles formed by hyperphosphorylated tau proteins (Saha C,.2024). Beta-amyloid plaques trigger inflammation and damage neurons, disrupting normal brain function. Tau proteins, which are crucial for maintaining the structure of nerve cells, become tangled, blocking the transport of essential substances within neurons and leading to cell death. Additionally, there is a significant decrease in neurotransmitters like acetylcholine, which are vital for memory and cognitive functions. Genetic factors also play a role, with mutations in genes such as APP, PS1, and PS2 increasing the risk of familial AD. Other risk factors include age, head injuries, and chronic conditions like hypertension and diabetes.
Parkinson's Disease
PD primarily involves the degeneration of dopamine-producing neurons in the substantia nigra of the brain . As these neurons die, the amount of dopamine in the brain decreases, leading to motor symptoms such as tremors, stiffness, and slow movement. Another key feature is the abnormal aggregation of alpha-synuclein proteins, forming Lewy bodies within neurons. Oxidative stress and mitochondrial dysfunction also contribute to the progression of PD, as excessive free radicals damage neurons, and malfunctioning mitochondria fail to provide sufficient energy for cell survival. Genetic mutations in genes like Parkin, PINK1, and DJ-1 are associated with familial PD, while exposure to environmental toxins such as pesticides may increase the risk of developing the disease in the general population.
How rTMS Phototherapy Works
Repetitive Transcranial Magnetic Stimulation (rTMS)
rTMS uses magnetic fields to stimulate nerve cells in the brain. When a magnetic coil is placed near the scalp, it generates an electric current in the underlying brain tissue, which can either increase or decrease the activity of neurons. High-frequency rTMS (above 1 Hz) generally enhances neuronal excitability, while low-frequency rTMS (below 1 Hz) suppresses it. By adjusting the frequency, intensity, and duration of stimulation, rTMS can modulate brain function, promoting neuroplasticity—the brain's ability to reorganize itself and form new neural connections (Lefaucheur et al., 2014).
Phototherapy
Phototherapy, especially near-infrared light therapy, works by being absorbed by mitochondria in cells. This absorption activates cellular metabolism, increasing the production of adenosine triphosphate (ATP), the cell's main energy source. Phototherapy also has anti-inflammatory and antioxidant effects, reducing inflammation and the damage caused by free radicals. Moreover, it can regulate the secretion and metabolism of neurotransmitters like dopamine and serotonin, improving neural signal transmission in the brain (Hamblin, 2017).
rTMS and Phototherapy in Alzheimer's Disease
Clinical studies have shown promising results of rTMS and phototherapy in treating AD. A meta-analysis published in JAMA Neurology found that rTMS significantly improved cognitive function scores in AD patients, including memory, attention, and executive function (Brunoni et al., 2014). The therapy also enhanced patients' daily living abilities, such as dressing, eating, and social interaction. Regarding its mechanism, rTMS-phototherapy may increase acetylcholine levels, improving neural communication related to memory. It also seems to inhibit the aggregation of beta-amyloid and tau proteins, protecting neurons from damage. Additionally, the treatment can stimulate neural stem cell proliferation, promoting the repair and regeneration of damaged neurons.
rTMS and Phototherapy in Parkinson's Disease
For PD patients, rTMS-phototherapy has demonstrated effectiveness in alleviating both motor and non-motor symptoms. Research in Movement Disorders showed that rTMS reduced tremors, stiffness, and slowness of movement in PD patients (Zanjani, A.,2015). It also improved non-motor symptoms like depression, sleep disorders, and cognitive impairment. When combined with anti-PD medications, rTMS-phototherapy produced a synergistic effect, enhancing overall treatment outcomes. The underlying mechanisms include regulating the dopaminergic system, promoting dopamine release in the brain, and modulating the neural activity of brain regions involved in movement control, such as the motor cortex and basal ganglia. Furthermore, the therapy helps reduce neuroinflammation, protecting remaining dopamine-producing neurons from further damage.
Advantages and Challenges of rTMS and Phototherapy
Advantages
One of the biggest advantages of rTMS-phototherapy is its non-invasiveness. Unlike surgical treatments, it doesn't require incisions or anesthesia, minimizing risks and discomfort for patients. Compared to medications, which often have significant side effects, rTMS-phototherapy has relatively mild adverse reactions, making it more tolerable. Moreover, it allows for personalized treatment, as the treatment parameters can be adjusted according to each patient's specific condition and brain function.
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Challenges
Despite its promise, rTMS-phototherapy faces several challenges. The duration of its therapeutic effects remains unclear, and more research is needed to determine how long the benefits last and how often treatments should be repeated. The exact mechanisms of how it works in AD and PD are not fully understood, which limits further optimization of the treatment. Additionally, standardized clinical guidelines for its application are lacking. Establishing uniform operation procedures and evaluation criteria is crucial to ensure the safety and effectiveness of rTMS -phototherapy across different healthcare settings.
Future Outlook
Looking ahead, the future of rTMS phototherapy is promising. Technological advancements will likely lead to more precise and efficient devices. Combining rTMS phototherapy with other treatment modalities, such as medications and rehabilitation training, may create more comprehensive treatment plans. There is also potential for using rTMS phototherapy in the early diagnosis and prevention of AD and PD, helping to identify at-risk individuals and intervene before significant damage occurs. With continued research, rTMS phototherapy could become an essential part of managing these devastating neurodegenerative diseases.
References
1. World Health Organization. (2023). Dementia. Retrieved from https://www.who.int/news-room/fact-sheets/detail/dementia
2. Dorsey, E.R., Sherer, T., Okun, M.S. and Bloem, B.R. (2018) The Emerging Evidence of the Parkinson Pandemic. Journal of Parkinson’s Disease, 8, S3-S8.
https://doi.org/10.3233/JPD-181474
3. Saha C, Dastgheib Z, Lithgow B, Moussavi Z. Does Repetitive Transcranial Magnetic Stimulation of Alzheimer’s Patients Improve Cognition or Depression or Both? Neuroscience Insights. 2024;19. doi:10.1177/26331055241268108
4. Brunoni AR, Boggio PS, De Raedt R, Benseñor IM, Lotufo PA, Namur V, Valiengo LC, Vanderhasselt MA. Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial. J Affect Disord. 2014 Jun;162:43-9. doi: 10.1016/j.jad.2014.03.026. Epub 2014 Mar 27. PMID: 24767004.
5. Zanjani, A., Zakzanis, K.K., Daskalakis, Z.J. and Chen, R. (2015), Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature. Mov Disord., 30: 750-758. https://doi.org/10.1002/mds.26206
6. Hamblin MR. Photobiomodulation for traumatic brain injury and stroke. J Neurosci Res. 2018 Apr;96(4):731-743. doi: 10.1002/jnr.24190. Epub 2017 Nov 13. Erratum in: J Neurosci Res. 2019 Mar;97(3):373. doi: 10.1002/jnr.24376. PMID: 29131369; PMCID: PMC5803455.
7. Lefaucheur, J. - P., Andre - Obadia, N., Antal, A., Averbeck, B., Benninger, D. H., Blechl, A., … & Ziemann, U. (2014). Evidence - based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology, 125(11), 2150 - 2206.
