• Dementia and Neurocognitive Disorders
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• v.23 no.4
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• pp.165-187
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• 2024

Lecanemab (product name Leqembi^®) is an anti-amyloid monoclonal antibody treatment approved for use in Korea for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. The Korean Dementia Association has created recommendations for the appropriate use of lecanemab to assist clinicians. These recommendations include selecting patients for administration, necessary pre-administration tests and preparations, administration methods, monitoring for amyloid related imaging abnormalities (ARIA), and communication with patients and caregivers. Lecanemab is recommended for patients with MCI or mild dementia who confirmed positive amyloid biomarkers, and should not be administered to patients with severe hypersensitivity to lecanemab or those unable to undergo magnetic resonance imaging (MRI) evaluation. To predict the risk of ARIA before administration, apolipoprotein E genotyping is conducted, and regular brain MRI evaluations are recommended to monitor for ARIA during treatment. The most common adverse reactions are infusion-related reactions, which require appropriate management upon occurrence. Additional caution is needed when co-administering with anticoagulants or tissue plasminogen activator due to the risk of macrohemorrhage. Clinicians should consider the efficacy and necessary conditions for administration, as well as the safety of lecanemab, to make a comprehensive decision regarding its use.

• Dementia and Neurocognitive Disorders
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• v.23 no.4
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• pp.188-201
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• 2024

Alzheimer's disease (AD), a leading cause of dementia, presents a formidable global health challenge intensified by the aging population. This review encapsulates the evolving landscape of AD diagnosis and treatment with a special focus on the innovative role of fluid biomarkers. Pathologically, AD is marked by amyloid beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau, which lead to synaptic dysfunction, neuronal loss, and cognitive decline. These pathological changes, commencing decades before symptom onset, underscore the need for early detection and intervention. Diagnosis traditionally relies on clinical assessment, neuropsychological testing, and neuroimaging techniques. However, fluid biomarkers in cerebrospinal fluid and blood, such as various forms of Aβ, total tau, phosphorylated tau, and neurofilament light chain, are emerging as less invasive, cost-effective diagnostic tools. These biomarkers are pivotal for early diagnosis, differential diagnosis, disease progression monitoring, and treatment response evaluation. The treatment landscape is shifting toward personalized medicine, highlighted by advancements in Aβ immunotherapies, such as lecanemab and donanemab. Demonstrating efficacy in phase III clinical trials, these therapies hold promise as tailored treatment strategies based on individual biomarker profiles. The integration of fluid biomarkers into clinical practice represents a significant advance in AD management, providing the potential for early and precise diagnosis, coupled with personalized therapeutic approaches. This heralds a new era in combating this debilitating disease.

• Korean Journal of Clinical Pharmacy
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• v.33 no.4
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• pp.290-304
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• 2023

Background: Innovative Alzheimer's disease drugs received approval in the United States in 2021 and 2023. This study aims to assess the safety and efficacy of these novel treatments, elucidate their mechanisms of action, and compare their impact on cognitive function improvement with approved drugs. Methods: We conducted a comprehensive search of pivotal clinical studies related to Alzheimer's disease treatments in PubMed/Medline, Embase, and the Cochrane Library databases from January 1st, 2020 to December 31st, 2022. Meta-analysis was performed using RevMan 5.4 software. Results: A total of 14 studies were included in this systematic review. When compared to the placebo, the new drugs did not exhibit a statistically significant effect on MMSE (Mini-Mental State Examination) (mean difference= -0.04, 95% confidence intervals [CIs]: -0.31, 0.23, N=3662, I²=0%). However, they demonstrated a significant impact on ADAS-cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) (standardized mean difference= -0.15, 95% CIs: -0.2, -0.1, N=6710, I²=17%). When compared to the approved drugs, the new drugs showed a statistically significantly lower effect on MMSE (test for subgroup difference Chi²=23.13, N = 5870, p<0.00001) but showed only a trend of decreased efficacy on ADAS-cog (Chi²=1.16, N = 8670, p=0.28). Conclusion: New drugs yielded diverse clinical endpoint results compared to the placebo, and in comparison to existing approved drugs, they exhibited lower efficacy in improving cognitive function. The safety profile of these new drugs, as reported in clinical trials, was generally well-tolerated.

• Korean Journal of Radiology
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• v.25 no.8
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• pp.726-741
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• 2024

Recent advancements in Alzheimer's disease treatment have focused on the elimination of amyloid-beta (Aβ) plaque, a hallmark of the disease. Monoclonal antibodies such as lecanemab and donanemab can alter disease progression by binding to different forms of Aβ aggregates. However, these treatments raise concerns about adverse effects, particularly amyloid-related imaging abnormalities (ARIA). Careful assessment of safety, especially regarding ARIA, is crucial. ARIA results from treatment-related disruption of vascular integrity and increased vascular permeability, leading to the leakage of proteinaceous fluid (ARIA-E) and heme products (ARIA-H). ARIA-E indicates treatment-induced edema or sulcal effusion, while ARIA-H indicates treatment-induced microhemorrhage or superficial siderosis. The minimum recommended magnetic resonance imaging sequences for ARIA assessment are T2-FLAIR, T2^* gradient echo (GRE), and diffusion-weighted imaging (DWI). T2-FLAIR and T2^* GRE are necessary to detect ARIA-E and ARIA-H, respectively. DWI plays a role in differentiating ARIA-E from acute to subacute infarcts. Physicians, including radiologists, must be familiar with the imaging features of ARIA, the appropriate imaging protocol for the ARIA workup, and the reporting of findings in clinical practice. This review aims to describe the clinical and imaging features of ARIA and suggest points for the timely detection and monitoring of ARIA in clinical practice.