Publications by authors named "So Yeon Jeon"

49 Publications

Validation of the Korean Version of the Anosognosia Questionnaire for Dementia.

Psychiatry Investig 2021 Apr 25;18(4):324-331. Epub 2021 Apr 25.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer's disease (AD) dementia.

Methods: We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated.

Results: Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI).

Conclusion: The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.
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http://dx.doi.org/10.30773/pi.2020.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103024PMC
April 2021

Association of Retinal Changes With Alzheimer Disease Neuroimaging Biomarkers in Cognitively Normal Individuals.

JAMA Ophthalmol 2021 May;139(5):548-556

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.

Importance: Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD.

Objectives: To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD.

Design, Setting, And Participants: This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020.

Main Outcomes And Measures: For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used.

Results: Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ-CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean [SD], 308.9 [18.4] vs 286.1 [22.5] μm; P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 [17.9] vs 103.8 [43.5] μm; P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ-CN group, particularly in ring 5 (41.3 [4.0] vs 38.2 [1.3] milliseconds; P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41, P = .005). The model to differentiate the Aβ+CN vs Aβ-CN groups derived from the results showed 90% accuracy.

Conclusions And Relevance: The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995126PMC
May 2021

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations.

J Alzheimers Dis 2021 ;81(1):287-295

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM.

Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments.

Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI.

Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD.

Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.
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http://dx.doi.org/10.3233/JAD-210036DOI Listing
January 2021

Blood Hemoglobin, Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study.

Front Aging Neurosci 2021 24;13:625511. Epub 2021 Feb 24.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies. A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured. A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect. The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.
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http://dx.doi.org/10.3389/fnagi.2021.625511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943867PMC
February 2021

Differential associations of age and Alzheimer's disease with sleep and rest-activity rhythms across the adult lifespan.

Neurobiol Aging 2021 May 22;101:141-149. Epub 2021 Jan 22.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea; Medical Research Center, Institute of Human Behavioral Medicine, Seoul National University Hospital, Seoul, South Korea; Interdisiplinary Program in Cognitive science, Seoul National University, Seoul, South Korea. Electronic address:

This study aimed to identify differences between physiological age-related and Alzheimer's disease (AD)-related alterations in sleep and rest-activity rhythm. All participants (n = 280; 20-90 years) underwent clinical assessments, [C] Pittsburgh compound B-positron emission tomography, and actigraphic monitoring. In cognitively normal adults without cerebral amyloid-β, older age was associated with earlier timing of circadian phase and robust rest-activity rhythm, but sleep quantity and quality were mostly unaffected by age. While preclinical AD was associated with earlier circadian timing, clinical AD exhibited later timing of daily rhythm and increased sleep duration. In conclusion, our findings suggest that older age itself leads to a more regular daily activity rhythm, but does not affect sleep duration. While preclinical AD made the effects of age-related phase advance more prominent, clinical AD was related to later circadian timing and increased sleep duration.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.006DOI Listing
May 2021

Alterations of amygdala-prefrontal cortical coupling and attention deficit/hyperactivity disorder-like behaviors induced by neonatal habenula lesion: normalization by Ecklonia stolonifera extract and its active compound fucosterol.

Behav Pharmacol 2021 Jun;32(4):308-320

Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Gyeongbuk.

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.
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http://dx.doi.org/10.1097/FBP.0000000000000620DOI Listing
June 2021

Genetic associations of in vivo pathology influence Alzheimer's disease susceptibility.

Alzheimers Res Ther 2020 11 19;12(1):156. Epub 2020 Nov 19.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Introduction: Although the heritability of sporadic Alzheimer's disease (AD) is estimated to be 60-80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.

Methods: Targeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using C-Pittsburgh Compound B positron emission tomography (PET), F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.

Results: We called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.

Conclusions: This study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.
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http://dx.doi.org/10.1186/s13195-020-00722-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678113PMC
November 2020

Long-Term Exposure to PM10 and in vivo Alzheimer's Disease Pathologies.

J Alzheimers Dis 2020 ;78(2):745-756

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Previous studies indicated an association between Alzheimer's disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10μm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association.

Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging.

Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10μm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant's residence.

Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure.

Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition.
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http://dx.doi.org/10.3233/JAD-200694DOI Listing
May 2021

Serum albumin and beta-amyloid deposition in the human brain.

Neurology 2020 08 20;95(7):e815-e826. Epub 2020 Jul 20.

From the Department of Neuropsychiatry (J.W.K.), Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, Gyeonggi-do; Department of Psychiatry (J.W.K.), Hallym University College of Medicine, Chuncheon, Gangwan-do; Institute of Human Behavioral Medicine (M.S.B., D.Y., D.Y.L.), Medical Research Center Seoul National University; Departments of Neuropsychiatry (J.H.L., D.Y.L.) and Radiology (K.M.K., C.-H.S.), Seoul National University Hospital; Department of Psychiatry (S.Y.J.), Chungnam National University Hospital, Daejeon; Sanggye Paik Hospital (B.K.S.), Department of Psychiatry, Inje University College of Medicine; Departments of Neuropsychiatry (J.-Y.L.) and Nuclear Medicine (S.A.S., Y.K.K.), SMG-SNU Boramae Medical Center; and Department of Psychiatry (J.-Y.L., D.Y.L.), Seoul National University College of Medicine, Republic of Korea.

Objectives: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral β-amyloid (Aβ) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain.

Methods: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [C] Pittsburgh compound B-PET, F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). Aβ positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures.

Results: Serum albumin level (as a continuous variable) was inversely associated with Aβ deposition and Aβ positivity. The low albumin group showed a significantly higher Aβ positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume.

Conclusions: Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.
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http://dx.doi.org/10.1212/WNL.0000000000010005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605506PMC
August 2020

Cushing Syndrome as a Result of an Adrenocorticotropin-Producing Large-Cell Neuroendocrine Carcinoma of the Ovary.

JCO Oncol Pract 2020 11 17;16(11):760-763. Epub 2020 Jul 17.

Division of Oncology and Hematology, Department of Internal Medicine, Jeonbuk National University Hospital-Jeonbuk National University Medical School, Jeonju, Republic of Korea.

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http://dx.doi.org/10.1200/OP.20.00189DOI Listing
November 2020

Serum Uric Acid, Alzheimer-Related Brain Changes, and Cognitive Impairment.

Front Aging Neurosci 2020 5;12:160. Epub 2020 Jun 5.

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, South Korea.

Background: Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies.

Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance.

Results: Serum UA level was significantly associated with AD-CM, but not with Aβ deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect.

Conclusion: The findings of the present study indicate that there is an association of low serum UA with AD-related cerebral hypometabolism, and whether this represents a causal relationship remains to be determined.
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http://dx.doi.org/10.3389/fnagi.2020.00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291838PMC
June 2020

Multiparity, Brain Atrophy, and Cognitive Decline.

Front Aging Neurosci 2020 3;12:159. Epub 2020 Jun 3.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

Background: Multiparity - grand multiparity (i.e., five or more childbirths) in particular - has been reported to have an association with increased risk of Alzheimer's disease (AD) dementia or related cognitive decline in women. However, the pathological links underlying this relationship are still unknown. This study was conducted to examine the relationships of multiparity with cerebral amyloid-beta (Aβ) deposition, brain atrophy, and white matter hyperintensities (WMHs).

Methods: In this study, total of 237 older women with 148 cognitively normal and 89 mild cognitive impairment from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. Participants underwent clinical and neuropsychological assessments in addition to C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. The associations of parity with Aβ deposition, hippocampal volume, cortical volume, WMH volume and mini-mental status examination (MMSE) score were examined.

Results: Participants with grand multiparity showed significantly reduced adjusted hippocampal volume, spatial pattern of atrophy for recognition of AD volume and spatial pattern of atrophy for recognition of brain aging volume even after controlling for potential confounders. Furthermore, MMSE score was also significantly lower in this group. In contrast, grand multiparity did not show any association with global Aβ retention, Aβ positivity rate, or WMH volume, regardless of covariates.

Conclusion: Our findings suggest that grand multiparity contributes to cognitive decline or increased dementia risk in older women by aggravating amyloid-independent hippocampal or cortical atrophy.
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http://dx.doi.org/10.3389/fnagi.2020.00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291884PMC
June 2020

Occurrence of lymphoplasmacytic lymphoma in a chronic myeloid leukemia patient following long-term treatment with tyrosine kinase inhibitors: A case report.

Medicine (Baltimore) 2020 May;99(19):e19962

Department of Internal Medicine.

Introduction: After tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 were introduced for the treatment of chronic myeloid leukemia, clinical outcomes have improved dramatically. However, together with the increase in the survival rate, a more frequent occurrence of secondary malignancies has been observed as well. TKIs have been demonstrated to be a risk factor of malignancies such as non-Hodgkin lymphoma, prostate cancer, and skin cancer. However, lymphoplasmacytic lymphoma (LPL) has never been reported as a secondary malignancy after TKI treatment in chronic myeloid leukemia (CML).

Patient Concerns: An 81-year-old male patient diagnosed with CML and treated with TKIs for a long period (15 years) was admitted due to a chief complaint of abdominal pain. A large abdominal mass was detected by imaging that included computed tomography.

Diagnosis: LPL was confirmed from biopsies after ultrasonography and sigmoidoscopy. Serum IgM level was increased and M protein and monoclonal gammopathy, IgM_kappa light chain type were detected.

Interventions: The patient received six cycles of R-CHOP chemotherapy.

Outcomes: After chemotherapy, he showed response. The sizes of the abdominal mass and lymph nodes decreased; moreover, serum M protein and IgM levels decreased, as well.

Conclusion: Herein, for the first time, we describe a patient who developed LPL as a secondary malignancy after administration of TKIs for the treatment of CML. Our observations indicate the importance of awareness of this secondary malignancy that can develop in CML patients treated with TKIs.
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http://dx.doi.org/10.1097/MD.0000000000019962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220158PMC
May 2020

Midlife Lifestyle Activities Moderate APOE ε4 Effect on Alzheimer's Disease Pathologies.

Front Aging Neurosci 2020 27;12:42. Epub 2020 Feb 27.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and Alzheimer's disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [C]-Pittsburgh-Compound-B-positron emission tomography (PET), [F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [ (SE) = - 627.580 (252.327), = -2.488, = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state ( = 0.004), but not at relatively low cognitive activity condition ( = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; (SE) = 0.004 (0.002), = 2.030, = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition ( < 0.001), whereas no such association was observed in relatively high physical activity state ( = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention.
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http://dx.doi.org/10.3389/fnagi.2020.00042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093017PMC
February 2020

Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study.

PLoS Med 2020 02 25;17(2):e1003022. Epub 2020 Feb 25.

Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.

Background: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain.

Methods And Findings: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history.

Conclusions: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.
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http://dx.doi.org/10.1371/journal.pmed.1003022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041799PMC
February 2020

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI.

Psychiatry Clin Neurosci 2020 May 23;74(5):303-310. Epub 2020 Feb 23.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Aim: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD-related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid-beta (Aβ) burden, AD-signature regional neurodegeneration, and white matter hyperintensities (WMH) in non-demented middle- and old-aged adults.

Methods: A total of 397 non-demented participants underwent comprehensive clinical and neuropsychological assessments, C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five-Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness.

Results: Neither neuroticism nor conscientiousness was associated with cerebral Aβ deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD-signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD-signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aβ deposition or WMH were not.

Conclusion: The present findings suggest that amyloid-independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.
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http://dx.doi.org/10.1111/pcn.12983DOI Listing
May 2020

Early risk stratification for diffuse large B-cell lymphoma integrating interim Deauville score and International Prognostic Index.

Ann Hematol 2019 Dec 11;98(12):2739-2748. Epub 2019 Nov 11.

Department of Internal Medicine, Chonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju, 54907, Republic of Korea.

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.
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http://dx.doi.org/10.1007/s00277-019-03834-4DOI Listing
December 2019

Normative Data for the Logical Memory Subtest of the Wechsler Memory Scale-IV in Middle-Aged and Elderly Korean People.

Psychiatry Investig 2019 Nov 28;16(11):793-799. Epub 2019 Oct 28.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: The purpose of this study is to identify the demographic variables that are affecting performances on the Logical Memory (LM) subtest included in the Korean version of the Wechsler Memory Scale (WMS)-IV and to provide normative data on the LM subtest for the middle-age and elderly Korean people.

Methods: The participants were 435 non-demented adults aging from 50 to 90 and with the educational level ranging from 0 to 21 years.

Results: Age and education were found to be significantly associated with performance on the LM subtest, while gender effect was not statistically significant. Therefore, we stratified the norm blocks by age and education. Age was divided into three groups: 50-59, 60-74, and 75-90 years. Education was stratified into three groups: 0-8 years, 9-12 years, and 13 years or more.

Conclusion: The normative data provided in the current study are expected to be useful in clinical and research settings to detect or define subtle changes in episodic memory in Korean adults and elderly, and can also be used for cross-cultural comparison of verbal episodic memory performance among elderly populations using different languages.
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http://dx.doi.org/10.30773/pi.2019.0061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877463PMC
November 2019

Coffee intake and decreased amyloid pathology in human brain.

Transl Psychiatry 2019 10 22;9(1):270. Epub 2019 Oct 22.

Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, 03080, Republic of Korea.

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer's disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aβ) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [C] Pittsburgh compound B-positron emission tomography (PET), [F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aβ positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.
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http://dx.doi.org/10.1038/s41398-019-0604-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805864PMC
October 2019

Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies.

Alzheimers Res Ther 2019 09 12;11(1):79. Epub 2019 Sep 12.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Background: Very little is known for the direction or causality of the relationship between lifetime sleep experiences and in vivo Alzheimer's disease (AD) pathologies. This study aimed to examine the relationship between sleep experiences during the young adulthood, midlife, and late-life periods and in vivo cerebral beta-amyloid (Aβ) deposition and AD signature regional neurodegeneration in cognitively normal (CN) old adults.

Methods: This study included 202 CN old adults who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) study. All participants underwent a comprehensive clinical assessment, [C] Pittsburgh Compound B positron emission tomography (PET), [F] Fluorodeoxyglucose-PET, and magnetic resonance imaging. The quality and duration of sleep were assessed for the following age periods: 20-30s, 40-50s, and the most recent month. All analyses were adjusted for age, gender, education, apolipoprotein E ε4 status, vascular risk score, Hamilton Depression Rating Scale score, and use of sleep medication.

Results: Bad sleep quality and short sleep duration during midlife were significantly associated with increased Aβ deposition and AD signature regional hypometabolism, respectively. Although current bad sleep quality appeared to be associated with increased Aβ accumulation, this association disappeared after controlling for the effects of midlife sleep quality. Neither the quality nor duration of sleep during young adulthood was related to Aβ burden or neurodegeneration.

Conclusions: Bad sleep quality during midlife increases pathological Aβ deposition in the brain, while short sleep duration during the same period accelerates regional hypometabolism.
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http://dx.doi.org/10.1186/s13195-019-0536-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739958PMC
September 2019

The effects of Engelhardtia chrysolepis Hance on long-term memory and potential dopamine involvement in mice.

Behav Pharmacol 2019 10;30(7):596-604

Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, Gyeongbuk, South Korea.

Engelhardtia chrysolepis Hance (ECH) is a perennial plant used in traditional medicine. A major active ingredient of ECH is astilbin (ASB), which has recently been shown to have neuroprotective effects as well as to affect catecholamine neurotransmissions in brain areas such as the prefrontal cortex. In this study, we investigated the effects of ECH and ASB on long-term memory in mice using a battery of behavioral tests. Acute ECH treatments dose-dependently facilitated nonspatial, but not spatial, memory. ECH treatments also upregulated expression of tyrosine hydroxylase, the enzyme mediating catecholamine synthesis, in neuroblastoma cell culture. Acute ASB treatments similarly improved nonspatial memory, whereas chronic ASB treatments improved both nonspatial and spatial memory. In accordance with such behavioral effects, the increased ratio of tissue concentrations of dopamine metabolites over dopamine in striatal regions was observed in mice with chronic ASB treatments. These results suggest that ECH and its active ingredient ASB may facilitate long-term memory by modulating catecholamine transmission.
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http://dx.doi.org/10.1097/FBP.0000000000000495DOI Listing
October 2019

A Multidomain Intervention for Modifying Lifestyle Habits Reduces the Dementia Risk in Community-Dwelling Older Adults: A Single-Blinded Randomized Controlled Pilot Study.

J Alzheimers Dis 2019 ;70(1):51-60

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

We aimed to examine the feasibility and effectiveness of a multidomain intervention including intensive and maintenance programs for reducing the risk of dementia in at-risk older adults. Community-dwelling older adults (aged ≥60 years) without dementia but having several risk factors for dementia (N = 32; 89% female; mean age±standard deviation, 76.8±4.7 years) were assigned to three parallel programs: intensive plus maintenance (INT+MNT), intensive only (INT-only), and active control. Subjects in INT+MNT and INT-only groups participated in a 4-week intensive group-based lifestyle modification program that focused on physical activity, vascular risk factors, dietary habits, cognitive activities, and social engagement. INT+MNT participants underwent an additional 20-week maintenance program to consolidate modified habits. The modified Australian National University-Alzheimer's Disease Risk Index (ANU-ADRI) score was used as the primary outcome measure for dementia risk. The changes in ANU-ADRI scores exhibited a significant group-by-time interaction: the INT+MNT group showed significant improvement at 24 weeks (β= -6.05; SE = 1.86; p = 0.002), while the INT-only group did not. Additional exploratory analyses showed that the reduction in ANU-ADRI scores was caused by changes in protective factors rather than in risk factors. The INT + MNT group also showed greater improvement in executive function at 4 and 24 weeks (both p = 0.044), whereas changes in global cognitive function did not reach significance (p = 0.055). A 24-week multidomain dementia prevention involving a maintenance strategy for sustaining modified lifestyle habits reduced the risk of dementia and improved executive function in at-risk older adults.
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http://dx.doi.org/10.3233/JAD-190016DOI Listing
September 2020

Plasma tau/amyloid-β1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer's disease.

Brain 2019 03;142(3):771-786

Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea.

One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-β1-42. We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-β1-42, and t-tau/amyloid-β1-42 with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-β1-42 in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-β1-42 correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-β1-42. These results indicate that combination of plasma tau and amyloid-β1-42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration.
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http://dx.doi.org/10.1093/brain/awy347DOI Listing
March 2019

Successful re-administration of Pazopanib in a patient with metastatic renal cell carcinoma and a history of Pazopanib-induced nephrotic syndrome: a case report.

BMC Nephrol 2019 01 3;20(1). Epub 2019 Jan 3.

Department of Internal Medicine, Chonbuk National University Medical School, 20, Geonji-ro, Deokjin-gu, Jeonju, 54907, Republic of Korea.

Background: Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.

Case Presentation: A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.

Conclusion: Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.
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http://dx.doi.org/10.1186/s12882-018-1181-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318841PMC
January 2019

Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration.

Neurobiol Aging 2019 03 16;75:62-70. Epub 2018 Nov 16.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

This study aimed to investigate the relationship of hypertension with beta-amyloid (Aβ) and neurodegeneration biomarkers of Alzheimer's disease (AD) and the modulating effect of apolipoprotein E-ε4 (APOE4). In total, 259 cognitively normal (CN) and 79 AD dementia older adults received clinical assessments including the evaluation for the presence of hypertension, [C]-Pittsburgh-compound-B-positron emission tomography, magnetic resonance imaging, and APOE genotyping. We used a clinical stage-specific approach, separately focusing on CN and AD dementia stages. For the CN group, individuals with hypertension showed reduced AD signature cortical thickness compared with those without hypertension. Subsequent subgroup analyses showed that hypertension was associated with reduced AD signature cortical thickness only in APOE4 noncarriers, whereas hypertension was associated with elevated Aβ deposition in APOE4 carriers. Meanwhile, regardless of APOE4 status, AD dementia patients with hypertension had significantly lower Aβ deposition than those without hypertension. In conclusion, the findings suggest that hypertension contributes to AD primarily through the reduction of brain reserve. In case of APOE4 carriers, however, hypertension seems to additionally facilitate AD process through amyloid-dependent pathway.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.11.001DOI Listing
March 2019

Neurometabolite changes in patients with complex regional pain syndrome using magnetic resonance spectroscopy: a pilot study.

Neuroreport 2019 01;30(2):108-112

Emotional Information and Communication Technology Association, Seoul, Republic of Korea.

The aim of this study was to investigate distinct neurometabolites in the right and left thalamus and insula of patients with complex regional pain syndrome (CRPS) compared with healthy controls using proton magnetic resonance spectroscopy. Levels of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), myo-inositol (ml), glutamine (Gln), glycerophosphocholine (GPC), glutathione (GSH), and alanine (Ala) relative to total creatine (tCr) levels, including creatine and phosphocreatine, were determined in the right and left thalamus and insula in 12 patients with CRPS compared with 11 healthy controls using magnetic resonance spectroscopy. Levels of NAAG/tCr and Ala/tCr were higher in patients with CRPS than in controls in the left thalamus. NAAG/tCr, ml/tCr, and Gln/tCr levels were higher but NAA/tCr levels were lower in the right insula of patients with CRPS compared with controls. There were negative correlations between GSH/tCr and pain score (McGill Pain Questionnaire) in the left thalamus. These findings are paramount to understand and determine all aspects of the complex pathophysiological mechanisms that underlie CRPS, including involvement of the central and parasympathetic nervous systems as well as oxidative stress and antioxidants. Thus, the distinct metabolites presented herein may be essential to understand a strong diagnostic and prognostic potential for CRPS and to develop effective medical treatments.
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http://dx.doi.org/10.1097/WNR.0000000000001168DOI Listing
January 2019

Prediction of Cerebral Amyloid With Common Information Obtained From Memory Clinic Practice.

Front Aging Neurosci 2018 3;10:309. Epub 2018 Oct 3.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.

Given the barriers prohibiting the broader utilization of amyloid imaging and high screening failure rate in clinical trials, an easily available and valid screening method for identifying cognitively impaired patients with cerebral amyloid deposition is needed. Therefore, we developed a prediction model for cerebral amyloid positivity in cognitively impaired patients using variables that are routinely obtained in memory clinics. Six hundred and fifty two cognitively impaired subjects from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer disease (KBASE) and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohorts were included in this study (107 amnestic mild cognitive impairment (MCI) and 69 Alzheimer's disease (AD) dementia patients for KBASE cohort, and 332 MCI and 144 AD dementia patients for ADNI-2 cohort). Using the cross-sectional dataset from the KBASE cohort, a multivariate stepwise logistic regression analysis was conducted to develop a cerebral amyloid prediction model using variables commonly obtained in memory clinics. For each participant, the logit value derived from the final model was calculated, and the probability for being amyloid positive, which was calculated from the logit value, was named the amyloid prediction index. The final model was validated using an independent dataset from the ADNI-2 cohort. The final model included age, sex, years of education, history of hypertension, apolipoprotein ε4 positivity, and score from a word list recall test. The model predicted that younger age, female sex, higher educational level, absence of hypertension history, presence of apolipoprotein ε4 allele, and lower score of word list recall test are associated with higher probability for being amyloid positive. The amyloid prediction index derived from the model was proven to be valid across the two cohorts. The area under the curve was 0.873 (95% confidence interval 0.815 to 0.918) for the KBASE cohort, and 0.808 (95% confidence interval = 0.769 to 0.842) for ADNI-2 cohort. The amyloid prediction index, which was based on commonly available clinical information, can be useful for screening cognitively impaired individuals with a high probability of amyloid deposition in therapeutic trials for early Alzheimer's disease as well as in clinical practice.
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http://dx.doi.org/10.3389/fnagi.2018.00309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178978PMC
October 2018

Prediction of Cerebral Amyloid With Common Information Obtained From Memory Clinic Practice.

Front Aging Neurosci 2018 3;10:309. Epub 2018 Oct 3.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.

Given the barriers prohibiting the broader utilization of amyloid imaging and high screening failure rate in clinical trials, an easily available and valid screening method for identifying cognitively impaired patients with cerebral amyloid deposition is needed. Therefore, we developed a prediction model for cerebral amyloid positivity in cognitively impaired patients using variables that are routinely obtained in memory clinics. Six hundred and fifty two cognitively impaired subjects from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer disease (KBASE) and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohorts were included in this study (107 amnestic mild cognitive impairment (MCI) and 69 Alzheimer's disease (AD) dementia patients for KBASE cohort, and 332 MCI and 144 AD dementia patients for ADNI-2 cohort). Using the cross-sectional dataset from the KBASE cohort, a multivariate stepwise logistic regression analysis was conducted to develop a cerebral amyloid prediction model using variables commonly obtained in memory clinics. For each participant, the logit value derived from the final model was calculated, and the probability for being amyloid positive, which was calculated from the logit value, was named the amyloid prediction index. The final model was validated using an independent dataset from the ADNI-2 cohort. The final model included age, sex, years of education, history of hypertension, apolipoprotein ε4 positivity, and score from a word list recall test. The model predicted that younger age, female sex, higher educational level, absence of hypertension history, presence of apolipoprotein ε4 allele, and lower score of word list recall test are associated with higher probability for being amyloid positive. The amyloid prediction index derived from the model was proven to be valid across the two cohorts. The area under the curve was 0.873 (95% confidence interval 0.815 to 0.918) for the KBASE cohort, and 0.808 (95% confidence interval = 0.769 to 0.842) for ADNI-2 cohort. The amyloid prediction index, which was based on commonly available clinical information, can be useful for screening cognitively impaired individuals with a high probability of amyloid deposition in therapeutic trials for early Alzheimer's disease as well as in clinical practice.
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http://dx.doi.org/10.3389/fnagi.2018.00309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178978PMC
October 2018

Brain Metabolites and Peripheral Biomarkers Associated with Neuroinflammation in Complex Regional Pain Syndrome Using [11C]-(R)-PK11195 Positron Emission Tomography and Magnetic Resonance Spectroscopy: A Pilot Study.

Pain Med 2019 03;20(3):504-514

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea.

Ojjective: The aim of this study was to find peripheral biomarkers and central metabolites affecting neuroinflammation in complex regional pain syndrome (CRPS) patients using [11C]-(R)-PK11195 positron emission tomography (PET) and magnetic resonance spectroscopy (MRS).

Methods: Using MRS and PET, we measured associations between neurometabolites and neuroinflammation in 12 CRPS patients and 11 healthy controls. Also, we investigated various peripheral parameters that may affect neuroinflammation in CRPS.

Results: We found positive correlations of Lipid (Lip)13a/total creatine (tCr) and Lip09/tCr with neuroinflammation, the distribution volume ratio (DVR) of [11C]-(R)-PK11195 in the right and left insula in CRPS patients. However, these correlations were not found in controls. High hemoglobin levels correlated with decreased neuroinflammation (the DVR of [11C]-(R)-PK11195) in the right thalamus and left insula in healthy controls. We found that high levels of glucose and pH correlated with increased neuroinflammation, but high levels of CO2, basophil, and creatinine were associated with decreased neuroinflammation in the left thalamus and the right and left insula in CRPS patients.

Conclusions: This is the first report indicating that elevated neuroinflammation levels are associated primarily with lipids in the brain and pH, glucose, CO2, basophil, and creatinine in the peripheral parameters in CRPS patients. Our results suggest that characterizing the peripheral biomarkers and central metabolites affecting neuroinflammation is essential to understanding the pathophysiology of CRPS.
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http://dx.doi.org/10.1093/pm/pny111DOI Listing
March 2019