Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects.

Patients with dementia suffer from psychological symptoms such as depression, agitation, and aggression. One purpose of dementia intervention is to manage patients’ inappropriate behaviors and psychological symptoms while taking into consideration their quality of life (QOL). Animal-assisted intervention (AAI) and pet-robot intervention (PRI) are effective intervention strategies for older people with cognitive impairment and dementia. In addition, AAI and PRI have been shown to have positive effects on behavioral and psychological symptoms of dementia (BPSD). However, studies into the association between AAI/PRI and BPSD have elicited inconsistent results. Thus, we performed a meta-analysis to investigate this association. We analyzed nine randomized controlled trials on AAI and PRI for dementia patients published between January 2000 and August 2019 and evaluated the impact of AAI/PRI on agitation, depression, and QOL. We found that AAI and PRI significantly reduce depression in patients with dementia. Subsequent studies should investigate the impact of AAI and PRI on the physical ability and cognitive function of dementia patients and conduct a follow-up to investigate their effects on the rate of progression and reduction of symptoms of dementia. Our research will help with neuropsychological and environmental intervention to delay or improve the development and progression of BPSD.

It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer’s disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD.

As the number of older adults increases, the prevalence of dementias, such as Alzheimer’s dementia (AD), vascular dementia, dementia with Lewy bodies, and frontotemporal dementias, also increases. Despite research into pharmacological approaches for treating diverse diseases, there is still no cure. Recently, novel non-pharmacological interventions are attracting attention. Non-pharmacological approaches include cognitive stimulation, alterations in diet, physical activity, and social engagement. Cognitive stimulating activities protect against the negative effects of cognitive decline caused by age-related neurogenerative diseases. Bilingualism is one form of cognitive stimulation that requires multiple aspects of brain activity and has been shown to delay the onset of dementia symptoms in patients by approximately 4–5 years as compared with monolingual patients through cognitive reserve. The purpose of this review was to bilingualism protects against cognitive decline associated with AD and other dementias. We discuss potential underlying neurological mechanisms, including: (1) stimulating adult neurogenesis, (2) enhancing synaptogenesis, (3) strengthening functional connectivity that bilingualism may delay clinical AD symptoms, (4) protecting white matter integrity, and (5) preserving gray matter density.

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