• Dementia and Neurocognitive Disorders
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• v.21 no.3
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• pp.83-92
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• 2022

Telomeres are located at the end of chromosomes. They are known to protect chromosomes and prevent cellular senescence. Telomere length shortening has been considered an important marker of aging. Many studies have reported this concept in connection with neurodegenerative disorders. Considering the role of telomeres, it seems that longer telomeres are beneficial while shorter telomeres are detrimental in preventing neurodegenerative disorders. However, several studies have shown that people with longer telomeres might also be vulnerable to neurodegenerative disorders. Before these conflicting results can be explained through large-scale longitudinal clinical studies on the role of telomere length in neurodegenerative disorders, it would be beneficial to simultaneously review these opposing results. Understanding these conflicting results might help us plan future studies to reveal the role of telomere length in neurodegenerative disorders. In this review, these contradictory findings are thoroughly discussed, with the aim to better understand the role of telomere length in neurodegenerative disorders.

• Annals of Clinical Neurophysiology
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• v.19 no.2
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• pp.101-112
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• 2017

Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD, which clearly needs to be investigated further in the future.

• Dementia and Neurocognitive Disorders
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• v.23 no.1
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• pp.54-66
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• 2024

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography (¹⁸F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of ¹⁸F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, ¹⁸F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: ¹⁸F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

• Korean Journal of Psychosomatic Medicine
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• v.15 no.2
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• pp.73-80
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• 2007

Anumber of prior studies have reported eye movement dysfunction in patients with dementia. The eye movement test which is non-invasive can evaluate the local brain function quantitatively. Therefore, it can be a useful method for characterizing regional brain abnormalities of patients with dementia. The aim of this paper is to review the literatures on eye movement abnormalities in dementia patients. Saccade system dysfunctions in Alzheimer disease include increased latency, reduced accuracy, and increased antisaccade error rates. Patients with frontotemporal dementia showed impaired reflexive saccade inhibition and increased latency and errors of antisaccade task. And delayed initiation of voluntary saccades, slow saccades, and increased errors and latency on antisaccade task were found in Huntington's disease. Patients with Parkinson’s disease dementia and dementia with Lewy bodies have characteristics of impaired in both reflexive saccade execution and complex saccade performance. However, there were few reports of abnormal eye movements in Creutzfeldt-Jakob disease; they could be found at the later stages after symptoms of dementia came to be evident, and secondary to cerebellar and vestibular involvement. Slowing of saccades and hypometric saccades might precede the supranuclear limitation of vertical gaze in PSP. Dysfunction of voluntary eyelid movements was a characteristic finding of PSP as well. In conclusion, patients with dementia can show various abnormal eye movements and they are related with cortial and subcortical brain dysfunctions. The research on localization of brain relevant to each symptom can promise more clinical implications of eye movement of dementia.

• Molecules and Cells
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• v.40 no.9
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• pp.613-620
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• 2017

The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid ${\beta}-peptide$ ($A{\beta}$) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than $A{\beta}$ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble $A{\beta}$ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased $A{\beta}$ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble $A{\beta}$ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie $A{\beta}-mediated$ neurodegeneration.

• Journal of Oriental Neuropsychiatry
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• v.29 no.2
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• pp.111-119
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• 2018

Objectives: To investigate the characteristics of patients diagnosed with dementia or mild cognitive impairment who are treated by means of a blend between Western and Korean medicine. Methods: We searched for outpatients with dementia or mild cognitive impairment by means of a collaboration between Western and Korean medicine from August 1, 2015, to July 31, 2017, through electronic medical records in Wonkwang Hospital. The records were retrospectively analyzed according to the patients' demographic and clinical characteristics, pathway of medical care, diagnostic tests, treatment, and medical expenses. Results: Thirteen patients were included in the analysis. Among them, six patients were diagnosed with mild cognitive impairment, five with dementia, Alzheimer's type, one patient with frontotemporal dementia, and one patient with unspecified dementia. Twelve of the thirteen patients were over 60 years of age. The number of pathways from the Dept. of Neurology to the Dept. of Neuropsychiatry of Korean Medicine was almost the same as the opposite pathway. The most used diagnostic test in Korean medicine was a neuropsychological test such as SNSB, MMSE and GDS. In Western medicine, hematology and neuroimaging were frequently used for patients. Acupuncture in Korean medicine and medication in Western medicine were the most frequently used. In Korean medicine, uncovered service costs were much higher than covered service costs,. whereas, in Western medicine, covered service costs were higher than uncovered service costs. Conclusions: This study describes the basic characteristics of dementia and mild cognitive impairment patients treated by a collaboration between Western and Korean medicine. Based on these results, a clinical pathway of the collaborative practice system between Western and Korean medicine for dementia patients needs to be developed.

• Analytical Science and Technology
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• v.28 no.5
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• pp.331-340
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• 2015

Mutations in Fused in Sarcoma (FUS) have been identified in patients with amyotrophic lateral sclerosis (ALS) or Frontotemporal Dementia (FTD). Pathological FUS is mis-localized to cytosol and forms aggregates associated with stress granules (SG), while FUS is normally localized to nucleus. However, it is largely unknown how pathological FUS forms SG-aggregates and which domains are responsible for this process. In this study, we examined cellular localization and aggregation of ALS-linked FUS missense mutants (P525L, R521C, R521H, R521G), analyzed the domains responsible for cytosolic FUS aggregation in HEK293T cells, and confirmed this in cultured mouse neurons. To do this, we firstly generated missense mutants of FUS and then examined their cellular localization. We found that P525L was mostly mis-localized to cytosol and formed FUS-positive SG aggregates while R521C, R521H, or R521G was localized to both nucleus and cytosol. To further characterize the domains required for aggregate formation of cytosolic FUS, we generated different domain-deletion mutants using FUS-∆17 which has a deletion of nuclear localization signal. Interestingly, cytosolic FUS without SYGQ and RGG1 domain or cytosolic FUS without RGG2-ZnF-RGG3 domain did not form FUS-positive SG aggregates, while cytosolic FUS without RRM domain generated more aggregates compared to FUS-∆17. Taken together, these data suggest that SYGQ-RGG1 or RGG2-ZnF-RGG3 domain contributes to formation of cytosolic aggregate, while RRM domain might interfere with FUS aggregation. Therefore, our studies will provide important insight for understanding cellular pathogenesis of neurodegeneration associated with FUS aggregate as well as finding therapeutic targets for ALS or FTD.

• Molecules and Cells
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• v.43 no.9
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• pp.821-830
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• 2020

Altered dendritic morphology is frequently observed in various neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the cellular and molecular basis underlying these pathogenic dendritic abnormalities remains largely unclear. In this study, we investigated dendritic morphological defects caused by dipeptide repeat protein (DPR) toxicity associated with G4C2 expansion mutation of C9orf72 (the leading genetic cause of ALS and FTD) in Drosophila neurons and characterized the underlying pathogenic mechanisms. Among the five DPRs produced by repeat-associated non-ATG translation of G4C2 repeats, we found that arginine-rich DPRs (PR and GR) led to the most significant reduction in dendritic branches and plasma membrane (PM) supply in Class IV dendritic arborization (C4 da) neurons. Furthermore, expression of PR and GR reduced the number of Golgi outposts (GOPs) in dendrites. In Drosophila brains, expression of PR, but not GR, led to a significant reduction in the mRNA level of CrebA, a transcription factor regulating the formation of GOPs. Overexpressing CrebA in PR-expressing C4 da neurons mitigated PM supply defects and restored the number of GOPs, but the number of dendritic branches remained unchanged, suggesting that other molecules besides CrebA may be involved in dendritic branching. Taken together, our results provide valuable insight into the understanding of dendritic pathology associated with C9-ALS/FTD.

• The Journal of Internal Korean Medicine
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• v.44 no.2
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• pp.187-196
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• 2023

Objective: This case study reported the effectiveness of adjuvant Korean therapy on gait disturbances induced by drug-induced Parkinsonism. Method: A patient suffering from frontotemporal lobe dementia was diagnosed with drug-induced Parkinsonism and treated with adjuvant Korean therapy, including herbal medicine and pharmaco-acupuncture. The evaluation was performed by monitoring the length of time and number of steps during an 8 m gait, using the Unified Parkinson's Disease Rating Scale (UPDRS). Results: After 17 days of adjuvant Korean therapy, the UPDRS score improved from 32 to 16. The length of time for the 8 m gait improved from 20 seconds to 14 seconds. The patient also showed a decrease in the number of steps during the 8 m gait from 43 to 22. Conclusion: This case suggests that adjuvant Korean therapy can be effective for drug-induced Parkinsonism.