Amyloid-related imaging abnormalities (ARIA) represent the most frequent adverse effect of lecanemab, a monoclonal antibody drug that targets amyloid beta. ARIA is observed in approximately 20% of patients who receive lecanemab. Most patients are asymptomatic; however, some develop serious neurological symptoms, and optimal management remains clinically challenging in such cases. In this review, I summarize the pathomechanism underlying ARIA and associated disorders, in addition to countermeasures for ARIA.
{"title":"[Pathogenesis and Treatment of Amyloid-related Imaging Abnormalities Caused by Disease-modifying Drugs in Alzheimer's Disease].","authors":"Hidekazu Tomimoto","doi":"10.11477/mf.1416202726","DOIUrl":"10.11477/mf.1416202726","url":null,"abstract":"<p><p>Amyloid-related imaging abnormalities (ARIA) represent the most frequent adverse effect of lecanemab, a monoclonal antibody drug that targets amyloid beta. ARIA is observed in approximately 20% of patients who receive lecanemab. Most patients are asymptomatic; however, some develop serious neurological symptoms, and optimal management remains clinically challenging in such cases. In this review, I summarize the pathomechanism underlying ARIA and associated disorders, in addition to countermeasures for ARIA.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The launch of lecanemab (an anti-Aβ antibody) has introduced a new treatment for Alzheimer's disease. In contrast to conventional therapeutic approaches to dementia, this drug requires new concepts in diagnosis, evaluation, and adverse effects. Specifically, evaluation of the efficacy of lecanemab is extremely important because this drug does not prevent but only slows the rate of disease progression. In this report, I have discussed future issues, including my personal viewpoint and also described the guidelines for promotion of the optimal use of lecanemab issued by the Ministry of Health, Labour, and Welfare.
{"title":"[Disease-modifying Drugs in Alzheimer's Disease: Indications and Efficacy Evaluation].","authors":"Atsushi Iwata","doi":"10.11477/mf.1416202725","DOIUrl":"https://doi.org/10.11477/mf.1416202725","url":null,"abstract":"<p><p>The launch of lecanemab (an anti-Aβ antibody) has introduced a new treatment for Alzheimer's disease. In contrast to conventional therapeutic approaches to dementia, this drug requires new concepts in diagnosis, evaluation, and adverse effects. Specifically, evaluation of the efficacy of lecanemab is extremely important because this drug does not prevent but only slows the rate of disease progression. In this report, I have discussed future issues, including my personal viewpoint and also described the guidelines for promotion of the optimal use of lecanemab issued by the Ministry of Health, Labour, and Welfare.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tau positron emission tomography (PET) is a neuroimaging technique that visualizes tau deposition using PET tracers that selectively bind to tau aggregates. Studies have reported the diagnostic and prognostic value of tau PET in Alzheimer's disease and other tauopathies. However, the binding profiles of tau PET drugs vary widely across tauopathies; therefore, an accurate understanding of the disease-specific characteristics is essential for interpretation of tau PET findings. In this review, we discuss the properties of tau-PET agents and their applications in various diseases.
tau正电子发射断层扫描(PET)是一种神经成像技术,它利用与tau聚集体选择性结合的PET示踪剂来观察tau沉积。研究报告显示,tau PET 对阿尔茨海默病和其他 tau 病具有诊断和预后价值。然而,tau PET药物的结合特征在不同的tau病症中差异很大;因此,准确了解疾病的特异性特征对于解释tau PET研究结果至关重要。在本综述中,我们将讨论tau-PET药物的特性及其在各种疾病中的应用。
{"title":"[Tau Positron Emission Tomography: Applications in Diagnosis and Prognosis of Various Diseases].","authors":"Keisuke Takahata, Manabu Kubota, Shin Kurose, Makoto Higuchi","doi":"10.11477/mf.1416202729","DOIUrl":"https://doi.org/10.11477/mf.1416202729","url":null,"abstract":"<p><p>Tau positron emission tomography (PET) is a neuroimaging technique that visualizes tau deposition using PET tracers that selectively bind to tau aggregates. Studies have reported the diagnostic and prognostic value of tau PET in Alzheimer's disease and other tauopathies. However, the binding profiles of tau PET drugs vary widely across tauopathies; therefore, an accurate understanding of the disease-specific characteristics is essential for interpretation of tau PET findings. In this review, we discuss the properties of tau-PET agents and their applications in various diseases.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease (AD) is a common dementia disorder in the elderly individuals, accounting for approximately 60-70% of all dementia cases. Recently, significant progress has been made in developing and approving anti-amyloid antibody drugs as one of the disease-modifying therapies (DMT) that aim to slow the progression of AD by targeting amyloid-beta accumulation in the brain. Notable drugs such as aducanumab, lecanemab, and donanemab have shown potential in clinical trials, leading to the approval of aducanumab and lecanemab, and approval is also expected for donanemab. Other anti-amyloid drugs such as remternetug and trontinemab are also under development. However, challenges remain, including adverse effects like amyloid-related imaging abnormalities (ARIA) and the need for addressing healthcare preparedness to support their use. This paper outlines the current status of DMT for AD, including the clinical trial results and current applications of these drugs. It also discusses the existing challenges to improve the safety and accessibility of DMTs.
{"title":"[Anti-amyloid Antibody Drugs as Disease-Modifying Therapies for Alzheimer's Disease].","authors":"Kenichiro Sato, Takeshi Iwatsubo","doi":"10.11477/mf.1416202723","DOIUrl":"10.11477/mf.1416202723","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a common dementia disorder in the elderly individuals, accounting for approximately 60-70% of all dementia cases. Recently, significant progress has been made in developing and approving anti-amyloid antibody drugs as one of the disease-modifying therapies (DMT) that aim to slow the progression of AD by targeting amyloid-beta accumulation in the brain. Notable drugs such as aducanumab, lecanemab, and donanemab have shown potential in clinical trials, leading to the approval of aducanumab and lecanemab, and approval is also expected for donanemab. Other anti-amyloid drugs such as remternetug and trontinemab are also under development. However, challenges remain, including adverse effects like amyloid-related imaging abnormalities (ARIA) and the need for addressing healthcare preparedness to support their use. This paper outlines the current status of DMT for AD, including the clinical trial results and current applications of these drugs. It also discusses the existing challenges to improve the safety and accessibility of DMTs.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neurodegenerative diseases represent the most common cause of dementia. Protein aggregation is upstream in the pathological mechanisms and is a therapeutic target in the development of disease-modifying drugs in this patient population. Notably, α-synuclein or DNA-binding protein of 43kDa (TDP-43) is commonly involved in the pathomechanisms that contribute to non-Alzheimer neurodegenerative diseases. Several immunotherapy clinical trials on α-synuclein have progressed to phase 2, and small-molecule therapeutics are ongoing. With regard to TDP-43, immunotherapies that target protein aggregates are currently being developed, and research is underway to investigate several drugs that target the associated causative gene. Further research is warranted for deeper insight into both disease-modifying drugs; biomarker tests need to be developed to determine their efficacy. However, both proteins aggregate and accumulate in the brain in many neurodegenerative diseases and dementia; therefore, they are therapeutically significant, and future progress is expected in research and development.
神经退行性疾病是导致痴呆症的最常见原因。蛋白质聚集是病理机制的上游,也是针对这类患者开发疾病调节药物的治疗目标。值得注意的是,α-突触核蛋白或 43kDa DNA 结合蛋白(TDP-43)通常参与了导致非阿尔茨海默氏症神经退行性疾病的病理机制。针对α-突触核蛋白的几项免疫疗法临床试验已进入第二阶段,小分子疗法也在进行中。关于 TDP-43,目前正在开发针对蛋白聚集体的免疫疗法,并正在研究几种针对相关致病基因的药物。要深入了解这两种改变疾病的药物,还需要进一步的研究;需要开发生物标志物测试来确定其疗效。不过,在许多神经退行性疾病和痴呆症中,这两种蛋白质都会在大脑中聚集和积聚;因此,它们具有重要的治疗意义,未来的研究和开发有望取得进展。
{"title":"[Disease-modifying Drugs for non-Alzheimer Dementias].","authors":"Takehiro Miyazaki, Shinji Higashi, Tetsuaki Arai","doi":"10.11477/mf.1416202733","DOIUrl":"10.11477/mf.1416202733","url":null,"abstract":"<p><p>Neurodegenerative diseases represent the most common cause of dementia. Protein aggregation is upstream in the pathological mechanisms and is a therapeutic target in the development of disease-modifying drugs in this patient population. Notably, α-synuclein or DNA-binding protein of 43kDa (TDP-43) is commonly involved in the pathomechanisms that contribute to non-Alzheimer neurodegenerative diseases. Several immunotherapy clinical trials on α-synuclein have progressed to phase 2, and small-molecule therapeutics are ongoing. With regard to TDP-43, immunotherapies that target protein aggregates are currently being developed, and research is underway to investigate several drugs that target the associated causative gene. Further research is warranted for deeper insight into both disease-modifying drugs; biomarker tests need to be developed to determine their efficacy. However, both proteins aggregate and accumulate in the brain in many neurodegenerative diseases and dementia; therefore, they are therapeutically significant, and future progress is expected in research and development.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amyloid PET plays a crucial role in the early diagnosis of Alzheimer's disease and the determination of the feasibility of disease-modifying therapies. It offers several advantages, including high sensitivity and specificity, minimal invasiveness, and the ability to provide spatial evaluation, all of which contribute to the optimization of dementia care. However, proper use and interpretation of the results require a thorough understanding of their limitations. Although careful consideration is necessary when using scans on asymptomatic individuals, clinical applications could broaden if preemptive treatments and high-precision individual risk assessments for the preclinical stage are developed.
淀粉样蛋白 PET 在阿尔茨海默病的早期诊断和确定改变病情疗法的可行性方面发挥着至关重要的作用。它具有多种优势,包括灵敏度和特异性高、微创性和提供空间评估的能力,所有这些都有助于优化痴呆症护理。然而,要正确使用和解释扫描结果,就必须充分了解其局限性。虽然在对无症状的人使用扫描时需要慎重考虑,但如果能开发出临床前阶段的先期治疗和高精度个体风险评估,就能扩大临床应用。
{"title":"[Clinical Implementation of Amyloid PET: Latest Findings and Practical Approaches in the Diagnosis and Treatment of Alzheimer's Disease].","authors":"Atsushi Michael Kimura, Hitoshi Shimada","doi":"10.11477/mf.1416202727","DOIUrl":"10.11477/mf.1416202727","url":null,"abstract":"<p><p>Amyloid PET plays a crucial role in the early diagnosis of Alzheimer's disease and the determination of the feasibility of disease-modifying therapies. It offers several advantages, including high sensitivity and specificity, minimal invasiveness, and the ability to provide spatial evaluation, all of which contribute to the optimization of dementia care. However, proper use and interpretation of the results require a thorough understanding of their limitations. Although careful consideration is necessary when using scans on asymptomatic individuals, clinical applications could broaden if preemptive treatments and high-precision individual risk assessments for the preclinical stage are developed.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several characteristic radiographic signs associated with various diseases are useful in neuroradiological practice; however, their clinical usefulness varies widely. This article presents some common signs and the associated pathological features, particularly those observed on computed tomography and magnetic resonance imaging or pathognomonic signs that are useful for accurate diagnosis, even in patients with rare diseases.
{"title":"[Clinical Utility of Radiographic Signs in Neuroradiology].","authors":"Suketaka Momoshima","doi":"10.11477/mf.1416202736","DOIUrl":"10.11477/mf.1416202736","url":null,"abstract":"<p><p>Several characteristic radiographic signs associated with various diseases are useful in neuroradiological practice; however, their clinical usefulness varies widely. This article presents some common signs and the associated pathological features, particularly those observed on computed tomography and magnetic resonance imaging or pathognomonic signs that are useful for accurate diagnosis, even in patients with rare diseases.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conventionally, APOE genetic testing has not been recommended as a component of the standard diagnostic and management practices for Alzheimer's disease. However, recent research highlights the importance of this test, particularly for assessment of the safety profile of anti-amyloid-β therapies. Therefore, the current United States guidelines for the administration of lecanemab explicitly advise APOE genetic testing. However, integration of this testing into clinical practice is associated with many clinical, ethical, legal, and economic challenges. It is important to initiate comprehensive discussions to address these multifaceted issues in Japan.
{"title":"[Significance and Response to APOE Genetic Testing in the Anti-amyloid-β Therapy Era].","authors":"Takayoshi Shimohata","doi":"10.11477/mf.1416202728","DOIUrl":"https://doi.org/10.11477/mf.1416202728","url":null,"abstract":"<p><p>Conventionally, APOE genetic testing has not been recommended as a component of the standard diagnostic and management practices for Alzheimer's disease. However, recent research highlights the importance of this test, particularly for assessment of the safety profile of anti-amyloid-β therapies. Therefore, the current United States guidelines for the administration of lecanemab explicitly advise APOE genetic testing. However, integration of this testing into clinical practice is associated with many clinical, ethical, legal, and economic challenges. It is important to initiate comprehensive discussions to address these multifaceted issues in Japan.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The advent of lecanemab is a hope not only for people with dementia and their families but also for society as a whole. However, the effectiveness of lecanemab is limited, and the need to inform patients of their dementia may emphasize negative aspects more than ever as "early diagnosis leads to early despair." In this situation, it is important to provide post-diagnostic support to make the "time spent living with dementia," which is prolonged by lecanemab, as meaningful as possible. In this review, the authors introduce the "Peer Support Activities for people with mild dementia and their families," a post-diagnosis support program for those diagnosed early in the course of the disease.
{"title":"[Lights and Shadows of Lecanemab: Post-diagnosis Support for People with Dementia Receiving Early Diagnosis].","authors":"Naoko Tsunoda, Mamoru Hashimoto","doi":"10.11477/mf.1416202724","DOIUrl":"10.11477/mf.1416202724","url":null,"abstract":"<p><p>The advent of lecanemab is a hope not only for people with dementia and their families but also for society as a whole. However, the effectiveness of lecanemab is limited, and the need to inform patients of their dementia may emphasize negative aspects more than ever as \"early diagnosis leads to early despair.\" In this situation, it is important to provide post-diagnostic support to make the \"time spent living with dementia,\" which is prolonged by lecanemab, as meaningful as possible. In this review, the authors introduce the \"Peer Support Activities for people with mild dementia and their families,\" a post-diagnosis support program for those diagnosed early in the course of the disease.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Headache is the most common condition encountered in neurological practice. However, despite the burden to patients, migraine, a typical primary headache, is not life-threatening, and evaluation shows no abnormalities; therefore, it is often treated using analgesics. Moreover, patients often do not visit hospitals and clinics because over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs are easily available. However, many patients continue to experience headaches. Migraine therapy has progressed remarkably following the advent of calcitonin gene-related peptide antibody drugs in recent years. Many patients with migraine do not visit hospitals and clinics and do not receive appropriate treatment. Therefore, in the future, neurologists will need to play a key role in patient education and in training physicians to enable accurate diagnosis of headaches.
{"title":"[Advances in Headache and Future Prospects].","authors":"Eiichiro Nagata","doi":"10.11477/mf.1416202709","DOIUrl":"10.11477/mf.1416202709","url":null,"abstract":"<p><p>Headache is the most common condition encountered in neurological practice. However, despite the burden to patients, migraine, a typical primary headache, is not life-threatening, and evaluation shows no abnormalities; therefore, it is often treated using analgesics. Moreover, patients often do not visit hospitals and clinics because over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs are easily available. However, many patients continue to experience headaches. Migraine therapy has progressed remarkably following the advent of calcitonin gene-related peptide antibody drugs in recent years. Many patients with migraine do not visit hospitals and clinics and do not receive appropriate treatment. Therefore, in the future, neurologists will need to play a key role in patient education and in training physicians to enable accurate diagnosis of headaches.</p>","PeriodicalId":52507,"journal":{"name":"Brain and Nerve","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}