Current Updates and Unmet Needs of Brain MRI-Based Artificial Intelligence Software for Patients With Neurodegenerative Diseases in the Republic of Korea

So Yeong Jeong,Chong Hyun Suh,Hwon Heo,Woo Hyun Shim,Sang Joon Kim 대한자기공명의과학회 2022 Investigative Magnetic Resonance Imaging Vol.26 No.4

In aging societies, incidences of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are increasing. Neurodegenerative diseases are bringing main challenges to the healthcare system in today’s world. Analyzing characteristic imaging patterns of patients with neurodegenerative diseases is important. Since objective and reliable imaging assessments and precise analyses can lead to early diagnosis of neurodegenerative diseases, imaging patterns are being increasingly investigated. Artificial intelligence (AI) analyzing brain MRI has been applied to neurodegenerative diseases, providing added value in early diagnosis. MRI-based AI software has been developed and studied worldwide, with some AI-based software already being used in actual clinical care. Currently, there are MRI-based volumetry and segmentation software available. There is also an unmet demand for the application of AI in neurodegenerative diseases. Here, we review current status and unmet needs for application of AI in neurodegenerative diseases. We also discuss current limitations of AI, suggestion for AI-based software, and how it can be clinically applied in the future.

퇴행성 뇌질환에서 뇌 자기공명영상 기반 인공지능 소프트웨어 활용의 현재

So Yeong Jeong,Chong Hyun Suh,Ho Young Park,Hwon Heo,Woo Hyun Shim,Sang Joon Kim 대한영상의학회 2022 대한영상의학회지 Vol.83 No.3

The incidence of neurodegenerative diseases in the older population has increased in recent years. A considerable number of studies have been performed to characterize these diseases. Imaging analysis is an important biomarker for the diagnosis of neurodegenerative disease. Objective and reliable assessment and precise detection are important for the early diagnosis of neurodegenerative diseases. Artificial intelligence (AI) using brain MRI applied to the study of neurodegenerative diseases could promote early diagnosis and optimal decisions for treatment plans. MRI-based AI software have been developed and studied worldwide. Representatively, there are MRI-based volumetry and segmentation software. In this review, we present the development process of brain volumetry analysis software in neurodegenerative diseases, currently used and developed AI software for neurodegenerative disease in the Republic of Korea, probable uses of AI in the future, and AI software limitations.

퇴행성 뇌질환에서의 분자영상

김재승,오승준,문대혁 대한의사협회 2009 대한의사협회지 Vol.52 No.2

Neurodegenerative diseases are highly morbid and widespread in the nation with aged population. Since these are progressive and irreversible diseases, early detection and differentiation of the disease are important for possible therapeutic intervention. Alzheimer s disease and Parkinson s disease are the most frequent and costly devastating neurodegenerative diseases. Recent advances of molecular imaging, especially positron emission tomography (PET) technique, allows non-invasive evaluation of not only regional cerebral metabolism or perfusion, but also the change of neurotransmission and presence of abnormal protein such as beta amyloid. In Parkinsonism, dopamine transporter and vesicular monoamine transporter imaging are useful in the diagnosis and evaluation of the disease progression since these provide information about the integrity of presynaptic striatal dopaminergic neurons. In Alzheimer s disease, beta-amyloid imaging can assess the amyloid deposition. It improves early diagnosis and possibility of a presymptomatic diagnostic biomarker; improves understanding of the natural history of amyloid deposition; and has the capability to directly measure the effects of newly developed anti-amyloid therapies. Cholinergic and microglial imaging can be also useful in the early diagnosis of dementia and improves understanding of insights into pathophysiology of neurodegenerative diseases. Therefore, the ability of molecular imaging to identify and quantify cerebral pathology has significant implications for early detection, differential diagnosis, and therapeutic monitoring in neurodegenerative diseases.

Amyloid beta plaque accumulation and memory function decline exacerbated by SAA1 in Alzheimer’s disease

Ji Won Ko,Zae Young Ryoo,Myoung Ok Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Neurodegenerative diseases like Parkinson’s disease (PD), Alzheimer’s diseases (AD) could be occurred from numerous reasons which result in neuronal death. Inflammation has been also regarded as one of the major causes of neurodegenerative disorders. In this respect, Serum amyloid A1 (SAA1) which is highly expressed in patients who have neurodegenerative disease implies that it takes some part in neurodegenerative disorders. SAA1 aggravates neuronal inflammation even though it is not an initiator of neuronal damage. Our previous studies revealed that liver-derived SAA1 aggregated in the brain by crossing the brain-blood barrier (BBB) present depressive-like behavior on mouse when it is overexpressing. However, it did not disclose how SAA1 regulates brain functions and why neurodegenerative patients show increasing pattern of SAA1. Therefore, we wondered the effects of SAA1 overexpression in neurodegenerative mouse model, and focused on the neuronal inflammation in Alzheimer’s disease. Especially, we established APP/SAA over-expressed double transgenic mice that both over-expressing amyloid precursor protein (APP)-c105 and SAA1 based on the Alzheimer"s disease (AD) research which has historically used transgenic (Tg) mouse models that overexpress mutant amyloid precursor protein (APP). With using this APP/SAA1 mice for scrutinizing the roles of SAA1 in the brain, we revealed that SAA1 overexpression brings about amyloid beta (Aβ) accumulation, glial activation, and memory decline. In other words, SAA1 overexpression increases neuroinflammation by making abundant amyloid beta in in the brain and trigger Alzheimer’s disease in the end.

Stem Cell Therapy for Neurodegenerative Diseases

김승현,이종진,오기욱 한양대학교 의과대학 2015 Hanyang Medical Reviews Vol.35 No.4

Neurodegenerative diseases are the hereditary and sporadic conditions which are characterized by progressive neuronal degeneration. Neurodegenerative diseases are emerging as the leading cause of death, disabilities, and a socioeconomic burden due to an increase in life expectancy. There are many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis, but we have no effective treatments or cures to halt the progression of any of these diseases. Stem cell-based therapy has become the alternative option to treat neurodegenerative diseases. There are several types of stem cells utilized; embryonic stem cells, induced pluripotent stem cells, and adult stem cell (mesenchymal stem cells and neural progenitor cells). In this review, we summarize recent advances in the treatments and the limitations of various stem cell technologies. Especially, we focus on clinical trials of stem cell therapies for major neurodegenerative diseases.

Disease predictability review using common biomarkers appearing in diabetic nephropathy and neurodegeneration of experimental animals

이순신 한국실험동물학회 2022 Laboratory Animal Research Vol.38 No.1

It is recently known that the kidney and brain have a very rich distribution of blood vessels, and the histological structures of micro-vessels are very similar. Therefore, a number of studies have reported that renal diseases like chronic kidney disease (CKD) caused by various causes have a very close relationship with the occurrence of neurodegenerative diseases. On the other hand, since diabetic nephropathy, which is caused by chronic inflammation, such as diabetes, often shows very different prognoses even in patients at the same clinical stage, the judgment of their disease prognosis will have a critical meaning in clinical practice. Recently, many studies of cerebro-renal interaction have been reported using experimental animals. The discovery of common biomarkers found in both organs can predict the prognosis of renal disease and the possibility of neurodegenerative disease progression. More associations can be found with novel common biomarkers found in the brain and kidneys that seem entirely unrelated. In that case, it will ultimately be a research field that can expand predictive models of patients' complex diseases through these biomarkers in clinical practice. It is presented biomarkers such as α-klotho, Nephrin, and Synaptopodin. These markers are observed in both the brain and kidney, and it has been reported that both organs show a very significant change in function according to their expression. Even though the brain and kidneys perform very independent functions, it is thought that it has a crucial diagnostic significance that the genes commonly expressed in both organs are functionally effective. With the discovery of novel biomarkers that share cerebro-renal interactions at the early stage of diabetic nephropathy, physicians can predict post-clinical symptoms and prevent severe neurodegenerative and cerebrovascular diseases. Therefore, further study for the diseases of these two organs in laboratory animals means that the field of research on this relationship can be expanded in the future. In the future, more attention and research will be needed on the possibility of prediction for the prevention of neurological diseases caused by CKD in disease animal models.

Neuronal autophagy and neurodegenerative diseases

손형진,심정희,김경희,하지영,한지영 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.2

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication,such as axons, dendrites and synapses,which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer’s disease,Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.

Asymmetry of Motor Symptoms and Neuronal Degeneration in Parkinson's Disease: A Brief Scoping Review

Miso Sophia Park(Miso Sophia Park),Sangsoo Park(Sangsoo Park),Wangjung Hur(Wangjung Hur),Horyong Yoo(Horyong Yoo) J-INSTITUTE 2022 Kinesiology Vol.7 No.2

Purpose: Parkinson’s disease(PD), the fastest-growing neurodegenerative disease, is a movement disorder that manifests unilaterally. Clinical studies, neuroimaging studies, and longitudinal studies all indicate that the clinical features and progression of PD are asymmetric. The asymmetry of PD is thought to be an important clue in understanding the disease's pathophysiology. The purpose of this study is to see how the concept of PD asym-metry evolved over time, to identify the different types of asymmetry that can be seen in PD, and to understand the clinical implications of the different types of asymmetry in PD. Method: The following were our review questions. (1)How has PD asymmetry research evolved over time? (2)What types of asymmetry can be seen in PD? (3)What are the clinical implications of the various types of asymmetry seen in PD? To investigate such questions, we used the keywords "Parkinson" and(“symmetry” or “asymmetry”) in PubMed. Articles about idiopathic Parkinson’s disease(iPD) patients with a clear concept of sym-metry or asymmetry that were peer-reviewed and written in English were included. The type of article, partici-pants, three main keywords, and the type of symmetry concepts in the study were extracted. We excluded studies that did not include patients with idiopathic PD or that did not have a clear concept of symmetry. Results: Based on a PubMed search, the number of published articles on iPD and symmetry gradually in-creased beginning in the 1980s. Of the 563 articles that were initially searched, 333 articles were related to both iPD and symmetry or asymmetry concepts. There were 171 articles on nervous system asymmetry, 133 on motor symptoms and gait asymmetry, 24 on disease presentation asymmetry, and 5 on anatomical or histological struc-tures asymmetry. The majority(n = 70) of the 171 studies on nervous system asymmetry dealt with lateralization of brain function and the resulting asymmetries in motor symptoms and disease manifestations in iPD patients. Conclusion: Asymmetry in iPD patients has mainly been studied based on nervous system asymmetry, motor symptoms, and overall disease presentation. Other types of asymmetry, such as asymmetry in anatomical and histological structures, have been studied in some studies. Asymmetry in iPD is not only an inherent feature of the disease; it also appears to be related to the disease's various symptoms and signs. As a result, more research is needed to better understand the pathophysiology of iPD and to provide iPD patients with a prognosis and advice for disease management.

Pharmacological intervention of early neuropathy in neurodegenerative diseases

Kwon, Min Jee,Kim, Jeong-Hoon,Kim, TaeSoo,Lee, Sung Bae Elsevier 2017 PHARMACOLOGICAL RESEARCH Vol.119 No.-

<P><B>Abstract</B></P> <P>Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neurodegenerative diseases, even before the occurrence of prominent neuronal death. However, until recently, the primary focus of studies regarding many neurodegenerative diseases has been on the massive cell death occurring at the late stages of disease progression. Thus, our understanding on early neuropathy in these diseases remains relatively limited. The complicated nature of various neuropathic features manifested early in neurodegenerative diseases suggests the involvement of a system-wide transcriptional regulation and epigenetic control. Epigenetic alterations and consequent changes in the neuronal transcriptome are now begun to be extensively studied in various neurodegenerative diseases. Upon the catastrophic incident of neuronal death in disease progression, it is utterly difficult to reverse the deleterious defects by pharmacological treatments, and therefore, therapeutics targeting the system-wide transcriptional dysregulation associated with specific early neuropathy is considered a better option. Here, we review our current understanding on the system-wide transcriptional dysregulation that is likely associated with early neuropathy shown in various neurodegenerative diseases and discuss the possible future developments of pharmaceutical therapeutics.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Percutaneous Endoscopic Gastrostomy Tube Insertion in Neurodegenerative Disease: A Retrospective Study and Literature Review

Pamela Sarkar,Alice Cole,Neil J. Scolding,Claire M. Rice 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.3

Background/Aims: With the notable exceptions of dementia, stroke, and motor neuron disease, relatively little is known about the safety and utility of percutaneous endoscopic gastrostomy (PEG) tube insertion in patients with neurodegenerative disease. We aimed to determine the safety and utility of PEG feeding in the context of neurodegenerative disease and to complete a literature review in order to identify whether particular factors need to be considered to improve safety and outcome. Methods: A retrospective case note review of patients referred for PEG insertion by neurologists in a single neuroscience center was conducted according to a pre-determined set of standards. For the literature review, we identified references from searches of PubMed, mainly with the search items “percutaneous endoscopic gastrostomy” and “neurology” or “neurodegenerative disease.”Results: Short-term mortality and morbidity associated with PEG in patients with neurological disease were significant. Age greater than 75 years was associated with poor outcome, and a trend toward adverse outcome was observed in patients with low serum albumin. Conclusions: This study highlights the relatively high risk of PEG in patients with neurodegenerative disease. We present points for consideration to improve outcome in this particularly vulnerable group of patients.