Clinical Approach of Low-Dose Whole-Brain Ionizing Radiation Treatment in Alzheimer’s Disease Dementia Patients1

Abstract

Our research team recently published two relevant papers. In one study, we have seen the acute effect of low-dose ionizing irradiation (LDIR) did not reduce the amyloid-β (Aβ) protein concentration in brain tissue, yet significantly improved synaptic degeneration and neuronal loss in the hippocampus and cerebral cortex. Surprisingly, in another study, we could see late effect that the LDIR-treated mice showed significantly improved learning and memory skills compared with those in the sham group. In addition, Aβ concentrations were significantly decreased in brain tissue. Furthermore, the pro-inflammatory cytokine tumor necrosis factor-α was decreased and the anti-inflammatory cytokine transforming growth factor-β was increased in the brain tissue of 5xFAD mice treated with LDIR. Definitive clinical results for the safety and efficacy of LDIR have not yet been published and, despite the promising outcomes reported during preclinical studies, LDIR can only be applied to patients with Alzheimer’s disease dementia when clinical results are made available. In addition, in the case of LDIR, additional large-scale clinical studies are necessary to determine the severity of Alzheimer’s disease dementia, indications for LDIR, the total dose to be irradiated, fraction size, and intervals of LDIR treatment. The purpose of this review is to summarize the mechanism of LDIR based on existing preclinical results in a way that is useful for conducting subsequent clinical research.

Helicobacter pylori and Alzheimer’s Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention

“…Low-dose radiation (LDR) has been reported to be an effective treatment strategy for AD . We utilized LDR as a positive treatment to compare the difference between AD + LDR and AD + MD + LDR, as well as the groups administered H. pylori .…”

“…H. pylori was more abundant in both AD and AD + MD human subjects, although other microbiota included Prevotella buccae, Coprococcus catus, Lactobacillus gasseri, and Bif idobacterium lactis, which were significantly reduced in abundance (Supplementary Figure 4A− Low-dose radiation (LDR) has been reported to be an effective treatment strategy for AD. 31 We utilized LDR as a positive treatment to compare the difference between AD + LDR and AD + MD + LDR, as well as the groups administered H. pylori. Figure 4 indicates fasting glucose and HOMA-IR levels increased after administration of H. pylori and decreased after LDR treatment (Figure 4A,B).…”

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure

“…However, the authors noted that heterogeneity between exposures and outcome measures made comparisons between cohorts difficult ( Pasqual et al, 2020 , 2021 ). Recent clinical trials are investigating the potential therapeutic effect of ionizing radiation on Alzheimer’s disease pathology but results from such clinical trials in humans have yet to be reported ( Chung et al, 2021 ; Jebelli et al, 2022 ). The evidence for ionizing radiation-induced late neurodegenerative disorders from the Japanese Atomic Bomb Survivors as well as other cohorts with accidental exposures is also mixed.…”

Effects of multidisciplinary collaborative nursing combined with cognitive stimulation therapy on cognitive function, quality of life, and daily activities in patients with Alzheimer’s disease

“…9 The primary concerns of the antibody include its inability to reach therapeutic objectives in the studies, and reported integrity difficulties, cost-effectiveness, possible side effects, need for routine observation, and criticism of the "amyloid burst theory". Chung et al 10 suggested low-dose ionizing radiation (LDIR) treatment as a therapy for AD and found that it reduced synapse degradation and loss of neuronal tissue in the frontal cerebrum and hippocampus, increased cognition and memorization abilities contrasted to the group, and enhanced neuronal deterioration. Additionally, the brain tissue was considerably reduced.…”