Clinical Practice Guideline for Dementia (Diagnosis and Evaluation):2021 Revised Edition

no abstract available.

Executive Summary of the 2021 International Conference of Korean Dementia Association: A Report From the Academic Committee of the Korean Dementia Association

Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer’s dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD’s diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes

Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.

Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes

Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.

Coping with Dementia in the Middle of the COVID-19 Pandemic

Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs.

Impaired Smooth Pursuit During Transient Global Amnesia

BACKGROUND AND PURPOSE: During transient global amnesia (TGA), selective impairment of episodic memory is assumed to occur due to alteration in the neuronal network between the hippocampus and parietooccipital cortices that also include a hub for smooth pursuit (SP) eye movements. This study aimed to determine whether SP is impaired during TGA, and to identify any anatomical and functional linkage present between the oculomotor and memory systems. METHODS: Within a median of 1.0 day of TGA, horizontal SP was evaluated in 145 patients with a target moving at peak velocities of 10°/s and 20°/s. The average SP gains of patients were compared with those of the age-matched controls. RESULTS: The patients with TGA showed lower SP gains in both directions for both peak target velocities. While the normal controls showed symmetric SP in the rightward and leftward directions, in the TGA patients the SP gain was lower during rightward than leftward SP regardless of bilaterality or the side of the lesions. CONCLUSIONS: The cortical regions processing information about visual motion appeared to be affected during or soon after an amnestic episode of TGA, and more so in the right hemisphere. This means that disturbed processing of dynamic visual information may be related to the impaired spatial orientation observed during TGA.

Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells

BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.

Multimodal Assessment of Neural Substrates in Computerized Cognitive Training: A Preliminary Study

BACKGROUND AND PURPOSE: Several studies have validated the clinical efficacy of computerized cognitive training applications. However, few studies have investigated the neural substrates of these training applications using simultaneous multimodal neuroimaging modalities. We aimed to determine the effectiveness of computerized cognitive training and corresponding neural substrates through a multimodal approach. METHODS: Ten patients with mild cognitive impairment (MCI), six patients with subjective memory impairment (SMI), and 10 normal controls received custom-developed computerized cognitive training in the memory clinic of a university hospital. All of the participants completed 24 sessions of computerized cognitive training, each lasting 40 minutes and performed twice weekly. They were assessed using neuropsychological tests (both computerized and conventional), electroencephalography, fluorodeoxyglucose positron-emission tomography (FDG-PET), volumetric magnetic resonance imaging (MRI), and diffusion-tensor imaging (DTI) at pre- and posttraining. RESULTS: The patients with MCI exhibited significant improvements in the trail-making test–black & white-B, and memory domain of the computerized cognitive assessment. Subjects with normal cognition exhibited significant improvements in scores in the language and attention-/psychomotor-speed domains. There were no significant changes in subjects with SMI. In the pre- and posttraining evaluations of the MCI group, FDG-PET showed focal activation in the left anterior insula and anterior cingulate after training. Volumetric MRI showed a focal increase in the cortical thickness in the rostral anterior cingulate. DTI revealed increased fractional anisotropy in several regions, including the anterior cingulate. CONCLUSIONS: The anterior cingulate and anterior insula, which are parts of the salience network, may be substrates for the improvements in cognitive function induced by computerized cognitive training.

Early Onset Alzheimer's Disease Presenting as Logopenic Primary Progressive Aphasia

No abstract available.

Hydrocephalus in a Patient with Alzheimer's Disease

BACKGROUND: Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimer's disease (AD). CASE REPORT: A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex. CONCLUSIONS: The patient of NPH was unresponsive to shunt therapy due to the development of AD.

Oldest Old Patients Should be Recruited More in Clinical Trials of Dementia

No abstract available.

Seasonal Variation in the Incidence of Transient Global Amnesia in South Korea

No abstract available.

Neurosyphilis Mimicking Creutzfeldt-Jakob Disease

BACKGROUND: As rapidly progressive dementia (RPD), general paresis and Creutzfeldt-Jakob disease (CJD) may have overlapping clinical presentation due to a wide variety of clinical manifestations. CASE REPORT: A 57-year-old man presented with rapid progressive cognitive decline, behavioral change, ataxic gait, tremor and pyramidal signs for 3 months. In addition to these multiple systemic involvements, positive result for the cerebrospinal fluid (CSF) 14-3-3 protein tentatively diagnosed him as probable CJD. However, due to increased serum rapid plasma reagin, venereal disease research laboratory, and fluorescent treponemal antibody-absorption reactivity in CSF, the final diagnosis was changed to general paresis. CONCLUSIONS: A patient with RPD needs to be carefully considered for differential diagnosis, among a long list of diseases. It is important to rule out CJD, which is the most frequent in RPD and is a fatal disease with no cure. Diagnostic criteria or marker of CJD, such as 14-3-3 protein, may be inconclusive, and a typical pattern in diffusion-weighted imaging is important to rule out other reversible diseases.

Risk Factors for Post-Lumbar Puncture Headache in a Study of Alzheimer's Disease Biomarkers

BACKGROUND AND PURPOSE: In memory clinics, the lumbar puncture (LP) is increasingly being used to evaluate cerebrospinal fluid for biomarkers of Alzheimer's disease (AD). Post-lumbar puncture headache (PLPH) is the most frequent complication of LP, and can prove to be a barrier for the performance of LP. METHODS: We retrospectively collected data from 59 subjects (patients with AD and cognitively healthy controls) who were enrolled in a study aimed to identify AD biomarkers via LP. In order to determine whether subjects experienced PLPH, we assessed recorded follow-up telephone interviews. To analyze the association between the occurrence of PLPH and several demographic- and procedure-related factors, a multiple logistic regression analysis with backward stepwise method was performed. RESULTS: The overall frequency of PLPH was 49.15%. PLPH was more frequent in younger subjects and clinical diagnosis was associated with PLPH. The use of cutting-edge needles was also suggested as a statistically significant factor in the development of PLPH, and was determined to be the only factor that could be modified in order to lower the frequency of PLPH. CONCLUSIONS: Age, clinical diagnosis, and needle type were all determined to be predictive factors of PLPH.

Utility of Oblique Coronal Images in Elderly and Cognitively Impaired Patients

No abstract available.

An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.

An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.

Longitudinal Clinical Changes of Non-Fluent/Agrammatic Primary Progressive Aphasia as Tau Spectrum Disorder: A Case Report

BACKGROUND: Tauopathies are a group of diseases caused by the accumulation of hyperphosphorylated tau protein in the central nervous system. Previous studies have revealed that there is considerable overlap in clinical, pathological, and genetic features among different taupathies. CASE REPORT: We report a patient with non-fluent/agrammatic primary progressive aphasia at the initial assessment. Over time, other symptoms belonging to corticobasal degeneration and progressive supranuclear palsy appeared in this patient. CONCLUSIONS: Clinical overlapping features in these disorders may represent different phenotypes of a single disease process.

Usefulness of the Informant Questionnaire on Cognitive Decline in the Elderly for Predicting Postoperative Delirium in Elderly Patients: A Pilot Study

BACKGROUND AND PURPOSE: Preexisting cognitive impairment is the strongest risk factor for delirium. We performed a pilot study to investigate whether the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which is a good complement to direct cognitive testing, could be useful for predicting postoperative delirium in elderly patients. METHODS: Between June 2013 and May 2014, 37 patients aged 70 years or older underwent the Korean version of the Mini-Mental State Examination (K-MMSE) and completed the IQCODE (IQCODE-K) before elective spine surgery in the Spine Center at the Seoul National University Bundang Hospital. Delirium was assessed daily from the day after surgery until discharge. A Mann-Whitney U test was used to compare the K-MMSE scores and the IQCODE-K scores between the groups with and without postoperative delirium. RESULTS: A total of three of 37 (8.1%) patients developed delirium during their hospital stay. The K-MMSE scores were not different between the two groups (p=0.105), whereas the IQCODE-K scores of patients with delirium were significantly higher than those of patients without delirium (p=0.021), indicating greater cognitive and functional decline over the previous 10 years. CONCLUSION: The IQCODE may be a suitable tool for assessing preoperative cognitive function and predicting postoperative delirium in elderly patients.

A case of fulminant Bacillus cereus meningoencephalitis after neuroplasty with white matter change

Bacillus cereus meningitis can show unusual presentation and very rapid progression associated with high mortality and unusual MRI findings. We report a 77-year-old man with fever and altered mentality after epidural neuroplasty for chronic lumbar spinal pain. Symptoms rapidly progressed over the 12 hours following surgery. He was diagnosed with meningoencephalitis by Bacillus cereus confirmed by CSF culture and DNA sequencing. He improved with antibiotics slowly although his mental state did not completely revert to his prior level. This case demonstrates the rapid and fulminant clinical picture produced by Bacillus cereus associated with neuroplasty. It also shows peculiar frontal white matter changes with hydrocephalus on MRI