Publications by authors named "Sang Won Seo"

352 Publications

Harmonisation of PET imaging features with different amyloid ligands using machine learning-based classifier.

Eur J Nucl Med Mol Imaging 2021 Jul 30. Epub 2021 Jul 30.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, South Korea.

Purpose: In this study, we used machine learning to develop a new method derived from a ligand-independent amyloid (Aβ) positron emission tomography (PET) classifier to harmonise different Aβ ligands.

Methods: We obtained 107 paired F-florbetaben (FBB) and F-flutemetamol (FMM) PET images at the Samsung Medical Centre. To apply the method to FMM ligand, we transferred the previously developed FBB PET classifier to test similar features from the FMM PET images for application to FMM, which in turn developed a ligand-independent Aβ PET classifier. We explored the concordance rates of our classifier in detecting cortical and striatal Aβ positivity. We investigated the correlation of machine learning-based cortical tracer uptake (ML-CTU) values quantified by the classifier between FBB and FMM.

Results: This classifier achieved high classification accuracy (area under the curve = 0.958) even with different Aβ PET ligands. In addition, the concordance rate of FBB and FMM using the classifier (87.5%) was good to excellent, which seemed to be higher than that in visual assessment (82.7%) and lower than that in standardised uptake value ratio cut-off categorisation (93.3%). FBB and FMM ML-CTU values were highly correlated with each other (R = 0.903).

Conclusion: Our findings suggested that our novel classifier may harmonise FBB and FMM ligands in the clinical setting which in turn facilitate the biomarker-guided diagnosis and trials of anti-Aβ treatment in the research field.
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http://dx.doi.org/10.1007/s00259-021-05499-6DOI Listing
July 2021

Increased telomere length in patients with frontotemporal dementia syndrome.

J Neurol Sci 2021 Jul 3;428:117565. Epub 2021 Jul 3.

Department of Neurology, Hanyang University College of Medicine, Gyeonggi-do, Republic of Korea.

Background: Telomeres are repetitive DNA sequences of TTAGGG at the ends of chromosomes. Many studies have shown that telomere shortening is associated with aging-related diseases, such as cardiovascular diseases, hypertension, diabetes, cancer, and various neurodegenerative diseases, including Alzheimer's disease, vascular dementia, Parkinson's disease, and dementia with Lewy bodies. However, changes in telomere length (TL) in patients with frontotemporal dementia (FTD) syndrome are unclear. Accordingly, in this study, we assessed TL in blood samples from patients with FTD syndrome.

Methods: Absolute TL was measured in peripheral blood leukocytes from 53 patients with FTD syndromes (25 with behavioral variant FTD, 19 with semantic variant primary progressive aphasia [PPA], six with nonfluent/agrammatic variant PPA, and three with amyotrophic lateral sclerosis [ALS] plus) and 28 cognitively unimpaired (CU) controls using terminal restriction fragment analysis.

Results: TL was significantly longer in the FTD group than in the CU group. All FTD subtypes had significantly longer TL than controls. There were no significant differences in TL among FTD syndromes. No significant correlations were found between TL and demographic factors in the FTD group.

Conclusions: Longer telomeres were associated with FTD syndrome, consistent with a recent report demonstrating that longer telomeres are related to ALS. Therefore, our results may support a shared biology between FTD and ALS. More studies with larger sample sizes are needed.
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http://dx.doi.org/10.1016/j.jns.2021.117565DOI Listing
July 2021

Effects of Electrical Automatic Massage on Cognition and Sleep Quality in Alzheimer's Disease Spectrum Patients: A Randomized Controlled Trial.

Yonsei Med J 2021 Aug;62(8):717-725

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Muscle relaxation following electrical automatic massage (EAM) has been found to reduce fatigue, depression, stress, anxiety, and pain in individuals with various conditions. However, the effects of EAM have not been extensively explored in patients with Alzheimer's disease (AD).

Materials And Methods: Here, we conducted a randomized controlled study to evaluate the effects of EAM on the cognitive and non-cognitive functions of patients with AD spectrum disorders.

Results: We found that EAM attenuated changes in attention-associated cognitive scores and subjective sleep quality relative to those in controls.

Conclusion: While further studies in a clinical setting are needed to support our findings, these encouraging results suggest that EAM may be an alternative therapy for the management of associated symptoms in AD (ClinicalTrials.gov ID: NCT03507192, 24/04/2018).
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http://dx.doi.org/10.3349/ymj.2021.62.8.717DOI Listing
August 2021

Cortical neuroanatomical changes related to specific neuropsychological deficits in subcortical vascular cognitive impairment.

Neuroimage Clin 2021 22;30:102685. Epub 2021 Apr 22.

Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; Neuroscience Center, Samsung Medical Center, Seoul 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, South Korea; Samsung Alzheimer Research Center and Center for Clinical Epidemiology Medical Center, Seoul, South Korea. Electronic address:

Objective: Neuropsychological test-specific neural substrates in subcortical vascular cognitive impairment (SVCI) are expected to differ from those in Alzheimer's disease-related cognitive impairment (ADCI) but the details are unclear. To determine neural substrates related to cerebral small vessel disease, we investigated the correlations between cognitive dysfunctions measured by standardized neuropsychological tests and cortical thickness in a large sample of participants with amyloid negative (Aβ (-)) SVCI.

Methods: One hundred ninety-eight participants with Aβ (-) SVCI were recruited from the memory clinic between November 2007 to August 2018. To acquire neural substrates, we performed linear regression using the scores of each neuropsychological test as a predictor, cortical thickness as an outcome, and age, sex, education years, intracranial volume and white matter hyperintensity (WMH) as confounders.

Results: Poor performances in each neuropsychological test were associated with cortical atrophy in certain brain regions regardless of WMH. Especially, not the medial temporal but the frontal and posterior cingulate regions with cortical atrophy were mainly associated with memory impairment. Poor performance in animal fluency was more likely to be associated with cortical atrophy in the left hemisphere, while poor performance in the visuospatial memory test was more likely to be associated with cortical atrophy in the right hemisphere.

Conclusions: Our findings suggested that cortical atrophy was an important factor of cognitive impairment in Aβ (-) SVCI regardless of WMH. Furthermore, our findings might give clinicians a better understanding of specific neural substrates of neuropsychological deficits in patients with SVCI.
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http://dx.doi.org/10.1016/j.nicl.2021.102685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102616PMC
July 2021

Helicobacter Pylori Infection Is Associated with Neurodegeneration in Cognitively Normal Men.

J Alzheimers Dis 2021 Jun 22. Epub 2021 Jun 22.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: An association between Helicobacter pylori (H. pylori) infection and dementia was reported in previous studies; however, the evidence is inconsistent.

Objective: In the present study, the association between H. pylori infection and brain cortical thickness as a biomarker of neurodegeneration was investigated.

Methods: A cross-sectional study of 822 men who underwent a medical health check-up, including an esophagogastroduodenoscopy and 3.0 T magnetic resonance imaging, was performed. H. pylori infection status was assessed based on histology. Multiple linear regression analyses were conducted to evaluate the relationship between H. pylori infection and brain cortical thickness.

Results: Men with H. pylori infection exhibited overall brain cortical thinning (p = 0.022), especially in the parietal (p = 0.008) and occipital lobes (p = 0.050) compared with non-infected men after adjusting for age, educational level, alcohol intake, smoking status, and intracranial volume. 3-dimentional topographical analysis showed that H. pylori infected men had cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas compared with non-infected men with the same adjustments (false discovery rate corrected, Q <  0.050). The association remained significant after further adjusting for inflammatory marker (C-reactive protein) and metabolic factors (obesity, dyslipidemia, fasting glucose, and blood pressure).

Conclusion: Our results indicate H. pylori infection is associated with neurodegenerative changes in cognitive normal men. H. pylori infection may play a pathophysiologic role in the neurodegeneration and further studies are needed to validate this association.
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http://dx.doi.org/10.3233/JAD-210119DOI Listing
June 2021

The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer's disease.

Sci Rep 2021 Jun 22;11(1):13050. Epub 2021 Jun 22.

Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.
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http://dx.doi.org/10.1038/s41598-021-92101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219697PMC
June 2021

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population.

Alzheimers Res Ther 2021 06 21;13(1):117. Epub 2021 Jun 21.

Department of Digital Health, SAIHST, Sungkyunkwan University, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population.

Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs.

Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain.

Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.
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http://dx.doi.org/10.1186/s13195-021-00854-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215820PMC
June 2021

The effect of body fatness on regional brain imaging markers and cognitive function in healthy elderly mediated by impaired glucose metabolism.

J Psychiatr Res 2021 Aug 11;140:488-495. Epub 2021 Jun 11.

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Department of Public Health, Yonsei University Graduate School, Seoul, 03722, Republic of Korea; Institute of Human Complexity and Systems Science, Yonsei University, Incheon, 21983, Republic of Korea. Electronic address:

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (β = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (β = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (β = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (β = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (β = -0.005; BC 95% CI = -0.013 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (β = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (β = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.
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http://dx.doi.org/10.1016/j.jpsychires.2021.06.011DOI Listing
August 2021

Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer's disease.

Alzheimers Res Ther 2021 06 14;13(1):113. Epub 2021 Jun 14.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Although few studies have shown that risk factors for Alzheimer's disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer's disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD.

Methods: We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories.

Results: APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD.

Conclusions: Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.
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http://dx.doi.org/10.1186/s13195-021-00857-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204422PMC
June 2021

Visual impairment increases the risk of dementia, especially in young males in a 12-year longitudinal follow-up study of a national cohort.

Sci Rep 2021 May 31;11(1):11393. Epub 2021 May 31.

Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

We investigated the effect of visual impairment (VI) on dementia development in a national cohort. In this 12-year nationwide population-based retrospective cohort study, national data were collected from National Health Insurance Cooperation of South Korea from 2002 to 2017, comprising 799,074 subjects selected from the dementia-free cohort representative of the Korean population. Crude hazard ratios (HRs) as well as age- and sex-adjusted HRs and confidence intervals (CIs) for the development of dementia were estimated using multivariable Cox regression models. VI significantly increased the risk of dementia with a HR of 2.726 (95% CI 2.251-3.300, p < 0.0001) after adjusting for age, sex, and interaction between age, sex, and VI. HR of interaction between VI and age for dementia was 0.539 (95% CI 0.436-0.667, p < 0.0001). In the sensitivity analysis after adjustment for age, sex, household income level, BMI and other comorbidities, VI showed higher risk for all the type of dementia (p < 0.0001). In subgroup analysis of VI, young males showed the highest risk for development of dementia with a HR of 2.687 (95% CI 2.219-3.254, p < 0.0001). VI significantly increased the risk of dementia in the study cohort, and young males with VI appeared to be the most susceptible to the development of dementia.
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http://dx.doi.org/10.1038/s41598-021-91026-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167134PMC
May 2021

Novel Alzheimer's disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers.

Transl Psychiatry 2021 05 19;11(1):296. Epub 2021 May 19.

Clinical Genomics Center, Samsung Medical Center, Seoul, South Korea.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E-07) and rs12594991 (P = 2.03E-07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.
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http://dx.doi.org/10.1038/s41398-021-01412-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134477PMC
May 2021

Combination of automated brain volumetry on MRI and quantitative tau deposition on THK-5351 PET to support diagnosis of Alzheimer's disease.

Sci Rep 2021 May 14;11(1):10343. Epub 2021 May 14.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea.

Imaging biomarkers support the diagnosis of Alzheimer's disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).
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http://dx.doi.org/10.1038/s41598-021-89797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121780PMC
May 2021

A case of paragonimiasis inducing bilateral pneumothorax with lung and liver involvement.

Asian Cardiovasc Thorac Ann 2021 Mar 28:2184923211006334. Epub 2021 Mar 28.

Department of Emergency Medicine, 65401Eulji University Hospital, Daejeon, Republic of Korea.

Pulmonary paragonimiasis can occasionally induce bilateral pneumothorax and cause lesions in ectopic organs such as the liver. We report the case of a 26-year-old man who had been treated for bilateral hydropneumothorax one month earlier and returned to the emergency center complaining of epigastric pain that had persisted for four months. After being diagnosed with pulmonary and hepatic paragonimiasis, he was treated with praziquantel and his condition improved without complications.
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http://dx.doi.org/10.1177/02184923211006334DOI Listing
March 2021

Predicting amyloid positivity in patients with mild cognitive impairment using a radiomics approach.

Sci Rep 2021 Mar 26;11(1):6954. Epub 2021 Mar 26.

Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea.

Predicting amyloid positivity in patients with mild cognitive impairment (MCI) is crucial. In the present study, we predicted amyloid positivity with structural MRI using a radiomics approach. From MR images (including T1, T2 FLAIR, and DTI sequences) of 440 MCI patients, we extracted radiomics features composed of histogram and texture features. These features were used alone or in combination with baseline non-imaging predictors such as age, sex, and ApoE genotype to predict amyloid positivity. We used a regularized regression method for feature selection and prediction. The performance of the baseline non-imaging model was at a fair level (AUC = 0.71). Among single MR-sequence models, T1 and T2 FLAIR radiomics models also showed fair performances (AUC for test = 0.71-0.74, AUC for validation = 0.68-0.70) in predicting amyloid positivity. When T1 and T2 FLAIR radiomics features were combined, the AUC for test was 0.75 and AUC for validation was 0.72 (p vs. baseline model < 0.001). The model performed best when baseline features were combined with a T1 and T2 FLAIR radiomics model (AUC for test = 0.79, AUC for validation = 0.76), which was significantly better than those of the baseline model (p < 0.001) and the T1 + T2 FLAIR radiomics model (p < 0.001). In conclusion, radiomics features showed predictive value for amyloid positivity. It can be used in combination with other predictive features and possibly improve the prediction performance.
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http://dx.doi.org/10.1038/s41598-021-86114-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997887PMC
March 2021

Amyloid Positivity in the Alzheimer/Subcortical-Vascular Spectrum.

Neurology 2021 04 15;96(17):e2201-e2211. Epub 2021 Mar 15.

From the Department of Neurology, Sungkyunkwan University School of Medicine (S.H.K., H.J., H.L., H.J.K., S.W.S., D.L.N.), Neuroscience Center (S.H.K., H.J., H.L., H.J.K., S.W.S., D.L.N.), and Stem Cell & Regenerative Medicine Institute (D.L.N.), Samsung Medical Center; Department of Neurology (S.H.K.), Korea University Guro Hospital, Korea University College of Medicine, Seoul; Chicago College of Osteopathic Medicine (M.E.K.), Midwestern University, IL; New York University (H.K.), NY; and Department of Health Sciences and Technology, SAIHST (D.L.N.), Sungkyunkwan University, Seoul, Korea.

Objective: We investigated the frequency of β-amyloid (Aβ) positivity in 9 groups classified according to a combination of 3 different cognition states and 3 distinct levels of white matter hyperintensities (WMH) (minimal, moderate, and severe) and aimed to determine which factors were associated with Aβ after controlling for WMH and vice versa.

Methods: A total of 1,047 individuals with subjective cognitive decline (SCD, n = 294), mild cognitive impairment (MCI, n = 237), or dementia (n = 516) who underwent Aβ PET scans were recruited from the memory clinic at Samsung Medical Center in Seoul, Korea. We investigated the following: (1) Aβ positivity in the 9 groups, (2) the relationship between Aβ positivity and WMH severity, and (3) clinical and genetic factors independently associated with Aβ or WMH.

Results: Aβ positivity increased as the severity of cognitive impairment increased (SCD [15.7%], MCI [43.5%], and dementia [76.2%]), whereas it decreased as the severity of WMH increased (minimal [54.5%], moderate [53.9%], and severe [41.0%]) or the number of lacunes (0 [59.0%], 1-3 [42.0%], and >3 [23.4%]) increased. Aβ positivity was associated with higher education, absence of diabetes, and presence of ε4 after controlling for cognitive and WMH status.

Conclusion: Our analysis of Aβ positivity involving a large sample classified according to the stratified cognitive states and WMH severity indicates that Alzheimer and cerebral small vessel diseases lie on a continuum. Our results offer clinicians insightful information about the association among Aβ, WMH, and cognition.
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http://dx.doi.org/10.1212/WNL.0000000000011833DOI Listing
April 2021

Comparison of Longitudinal Changes of Cerebral Small Vessel Disease Markers and Cognitive Function Between Subcortical Vascular Mild Cognitive Impairment With and Without Variant: A 5-Year Follow-Up Study.

Front Neurol 2021 25;12:586366. Epub 2021 Feb 25.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without variant [(+) svMCI vs. (-) svMCI]. We prospectively recruited patients with svMCI and screened for variants by sequence analysis for mutational hotspots in the gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the (+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the (-) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.
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http://dx.doi.org/10.3389/fneur.2021.586366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947323PMC
February 2021

New assessment for residential greenness and the association with cortical thickness in cognitively healthy adults.

Sci Total Environ 2021 Jul 1;778:146129. Epub 2021 Mar 1.

Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea. Electronic address:

Background: Recent evidence suggests that neurological health could be improved with the intervention of local green space. A few studies adopted cortical thickness, as an effective biomarker for neurodegenerative disorder, to investigate the association with residential greenness. However, they relied on limited data sources, definitions or applications to assess residential greenness. Our cross-sectional study assessed individual residential greenness using an alternative measure, which provides a more realistic definition of local impact and application based on the type of area, and investigated the association with cortical thickness.

Methods: The study population included 2542 subjects who participated in the medical check-up program at the Health Promotion Center of the Samsung Medical Center in Seoul, Korea, from 2008 to 2014. The cortical thickness was calculated by each of the four and global lobes from brain MRI. For greenness, we used the enhanced vegetation index (EVI) that detects canopy structural variation by adjusting background noise based on satellite imagery data. To assess individual exposure to residential greenness, we computed the maximum annual EVI before the date of a medical check-up and averaged it within 750 m from subjects' homes to represent an average walking distance. Finally, we assessed the association with cortical thickness by urban and non-urban populations using multiple linear regression adjusting for individual characteristics.

Results: The average global cortical thickness and EVI were 3.05 mm (standard deviation = 0.1 mm) and 0.31 (0.1), respectively. An interquartile range increase in EVI was associated with 11 μm (95% confidence interval = 3-20) and 9 μm (1-16) increases in cortical thickness of the parietal and occipital regions among the urban population. We did not find associations in non-urban subjects.

Conclusions: Our findings confirm the association between residential greenness and neurological health using alternative exposure assessments, indicating that high exposure to residential greenness can prevent neurological disorders.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146129DOI Listing
July 2021

Prediction of tau accumulation in prodromal Alzheimer's disease using an ensemble machine learning approach.

Sci Rep 2021 Mar 11;11(1):5706. Epub 2021 Mar 11.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

We developed machine learning (ML) algorithms to predict abnormal tau accumulation among patients with prodromal AD. We recruited 64 patients with prodromal AD using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Supervised ML approaches based on the random forest (RF) and a gradient boosting machine (GBM) were used. The GBM resulted in an AUC of 0.61 (95% confidence interval [CI] 0.579-0.647) with clinical data (age, sex, years of education) and a higher AUC of 0.817 (95% CI 0.804-0.830) with clinical and neuropsychological data. The highest AUC was 0.86 (95% CI 0.839-0.885) achieved with additional information such as cortical thickness in clinical data and neuropsychological results. Through the analysis of the impact order of the variables in each ML classifier, cortical thickness of the parietal lobe and occipital lobe and neuropsychological tests of memory domain were found to be more important features for each classifier. Our ML algorithms predicting tau burden may provide important information for the recruitment of participants in potential clinical trials of tau targeting therapies.
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http://dx.doi.org/10.1038/s41598-021-85165-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970986PMC
March 2021

Cognitive trajectories of patients with focal ß-amyloid deposition.

Alzheimers Res Ther 2021 02 19;13(1):48. Epub 2021 Feb 19.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

Methods: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.

Results: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.

Conclusions: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.
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http://dx.doi.org/10.1186/s13195-021-00787-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896397PMC
February 2021

Disease progression modelling from preclinical Alzheimer's disease (AD) to AD dementia.

Sci Rep 2021 Feb 18;11(1):4168. Epub 2021 Feb 18.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

To characterize the course of Alzheimer's disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.
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http://dx.doi.org/10.1038/s41598-021-83585-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893024PMC
February 2021

-GlcNAcylation ameliorates the pathological manifestations of Alzheimer's disease by inhibiting necroptosis.

Sci Adv 2021 Jan 13;7(3). Epub 2021 Jan 13.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

-GlcNAcylation (-linked β--acetylglucosaminylation) is notably decreased in Alzheimer's disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered -GlcNAcylation, β-amyloid (Aβ) accumulation, and necroptosis are unclear. Here, we found that -GlcNAcylation plays a protective role in AD by inhibiting necroptosis. Necroptosis was increased in AD patients and AD mouse model compared with controls; however, decreased necroptosis due to -GlcNAcylation of RIPK3 (receptor-interacting serine/threonine protein kinase 3) was observed in 5xFAD mice with insufficient -linked β--acetylglucosaminase. -GlcNAcylation of RIPK3 suppresses phosphorylation of RIPK3 and its interaction with RIPK1. Moreover, increased -GlcNAcylation ameliorated AD pathology, including Aβ burden, neuronal loss, neuroinflammation, and damaged mitochondria and recovered the M2 phenotype and phagocytic activity of microglia. Thus, our data establish the influence of -GlcNAcylation on Aβ accumulation and neurodegeneration, suggesting -GlcNAcylation-based treatments as potential interventions for AD.
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http://dx.doi.org/10.1126/sciadv.abd3207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806231PMC
January 2021

Machine Learning for the Prediction of Amyloid Positivity in Amnestic Mild Cognitive Impairment.

J Alzheimers Dis 2021 ;80(1):143-157

Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Amyloid-β (Aβ) evaluation in amnestic mild cognitive impairment (aMCI) patients is important for predicting conversion to Alzheimer's disease. However, Aβ evaluation through Aβ positron emission tomography (PET) is limited due to high cost and safety issues.

Objective: We therefore aimed to develop and validate prediction models of Aβ positivity for aMCI using optimal interpretable machine learning (ML) approaches utilizing multimodal markers.

Methods: We recruited 529 aMCI patients from multiple centers who underwent Aβ PET. We trained ML algorithms using a training cohort (324 aMCI from Samsung medical center) with two-phase modelling: model 1 included age, gender, education, diabetes, hypertension, apolipoprotein E genotype, and neuropsychological test scores; model 2 included the same variables as model 1 with additional MRI features. We used four-fold cross-validation during the modelling and evaluated the models on an external validation cohort (187 aMCI from the other centers).

Results: Model 1 showed good accuracy (area under the receiver operating characteristic curve [AUROC] 0.837) in cross-validation, and fair accuracy (AUROC 0.765) in external validation. Model 2 led to improvement in the prediction performance with good accuracy (AUROC 0.892) in cross validation compared to model 1. Apolipoprotein E genotype, delayed recall task scores, and interaction between cortical thickness in the temporal region and hippocampal volume were the most important predictors of Aβ positivity.

Conclusion: Our results suggest that ML models are effective in predicting Aβ positivity at the individual level and could help the biomarker-guided diagnosis of prodromal AD.
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http://dx.doi.org/10.3233/JAD-201092DOI Listing
January 2021

Identification of Cathepsin D as a Plasma Biomarker for Alzheimer's Disease.

Cells 2021 Jan 12;10(1). Epub 2021 Jan 12.

Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.

Although Alzheimer's disease (AD) is the most common neurodegenerative disease, there are still no drugs available to treat or prevent AD effectively. Here, we examined changes in levels of selected proteins implicated in the pathogenesis of AD using plasma samples of control subjects and patients with cognition impairment. To precisely categorize the disease, fifty-six participants were examined with clinical cognitive tests, amyloid positron emission tomography (PET) scan, and white matter hyperintensities scored by magnetic resonance imaging. Plasma cathepsin D levels of the subjects were examined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Correlation of plasma cathepsin D levels with AD-related factors and clinical characteristics were examined by statistical analysis. By analyzing quantitative immunoblot and ELISA, we found that the plasma level of cathepsin D, a major lysosomal protease, was decreased in the group with amyloid plaque deposition at the brain compared to the control group. The level of plasma cathepsin D was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores. In addition, our integrated multivariable logistic regression model suggests the high performance of plasma cathepsin D level for discriminating AD from non-AD. These results suggest that the plasma cathepsin D level could be developed as a diagnostic biomarker candidate for AD.
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http://dx.doi.org/10.3390/cells10010138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827175PMC
January 2021

Ca α2δ Autoimmune Encephalitis: A Novel Antibody and its Characteristics.

Ann Neurol 2021 04 26;89(4):740-752. Epub 2021 Jan 26.

Department of Physiology and Neuroscience Research Center, Seoul National University College of Medicine, Seoul, South Korea.

Objective: Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism.

Method: We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons.

Results: Two patients had a novel antibody against Ca α2δ (voltage-gated calcium channel alpha-2/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a Ca α2δ-overexpressing cell line. Knockdown of Ca α2δ expression in cultured neurons turned off the immunoreactivity of the antibody from the patients to the neurons. The patients were associated with preceding meningitis or neuroendocrine carcinoma and responded to immunotherapy. In cultured neurons, the antibody reduced neurotransmitter release from presynaptic nerve terminals by interfering with tight coupling of calcium channels and exocytosis.

Interpretation: Here, we discovered a novel autoimmune encephalitis associated with anti-Ca α2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. ANN NEUROL 2021;89:740-752.
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http://dx.doi.org/10.1002/ana.26017DOI Listing
April 2021

Association Between Amyloid Accumulation and Sleep in Patients With Idiopathic REM Sleep Behavior Disorder.

Front Neurol 2020 3;11:547288. Epub 2020 Dec 3.

Department of Neurology, Neuroscience Center, School of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.

Amyloid-beta protein may lead to sleep disturbance and eventually develop cognitive impairment. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a predictor of neurodegeneration, yet there have been limited studies evaluating the relationship between cognitive decline and amyloid accumulation in iRBD patients. The aim of this study is to investigate the clinical and sleep characteristics of iRBD patients and its association with amyloid deposition. We enroll 23 iRBD patients (mean age, 65.8 years; male, 73.9%), and their mean history of clinically suspected RBD was 6.5 years. All underwent 18F-flutemetamol amyloid PET completed polysomnography (PSG) and questionnaires. Patients were classified into two groups according to amyloid deposition as amyloid positive and negative. Clinical and sleep parameters were compared between groups and were correlated with amyloid deposition, calculated as a standardized uptake value ratio (SUVR). Four patients (17.4%) were revealed to be amyloid positive, and they showed increased percentage of wake after sleep onset (WASO), stage N1, and stage N2 sleep and worse on the Stroop Word Color Test compared to amyloid negative patients. Global SUVR was correlated with total sleep time, sleep efficiency, WASO, and N1 sleep, and these sleep parameters were associated with a part of default mode network of brains such as orbitofrontal, dorsolateral pre-frontal, and left temporal areas. iRBD patients with amyloid deposition have worse sleep quality than patients without amyloid. Relationship between fragmented sleep and amyloid deposition in the default mode network may be crucial to elucidate the disease progress of iRBD.
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http://dx.doi.org/10.3389/fneur.2020.547288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744751PMC
December 2020

Mean and visit-to-visit variability of glycemia and left ventricular diastolic dysfunction: A longitudinal analysis of 3025 adults with serial echocardiography.

Metabolism 2021 03 26;116:154451. Epub 2020 Nov 26.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Objective: We aimed to determine the mean glucose thresholds to increase the risk of left ventricular diastolic dysfunction (LVDD) and whether visit-to-visit variability of fasting plasma glucose (FPG) and glycated hemoglobin (A1C) could independently increase the risk in a cohort with serial echocardiography.

Methods: This was a 3.5-year (range, 0.5-8.3) retrospective longitudinal cohort study of 3025 adults (age, 55.15 ± 7.6 years; without diabetes, n = 2755) with LV ejection fraction > 50% by serial echocardiography between 2006 and 2016. Mean, standard of deviation (SD) and coefficient of variation (CV) of FPG and A1C obtained from three consecutive measurements preceding the first echocardiography. The definition of LVDD in this study was primarily based on early peak mitral inflow velocity and early diastolic mitral annulus motion velocity.

Results: LVDD developed in 611/3025 subjects (20.2%). Cox proportional hazard models showed increased adjusted hazard ratios (HRs) for incident LVDD in the highest quartile of FPG-mean (HR 1.76, 95% confidence interval [CI]; 1.36-2.30), FPG-SD (HR 1.63, 95% CI; 1.27-2.09), FPG-CV (HR 1.47, 95% CI; 1.15-1.89), and A1C-mean (HR 1.83, 95% CI; 1.41-2.38) versus the lowest quartile, which was consistent even in subjects without diabetes. Mean glucose thresholds for the increased risk were below the lower limits for pre-diabetes.

Conclusions: In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD.
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http://dx.doi.org/10.1016/j.metabol.2020.154451DOI Listing
March 2021

Diagnostic Accuracy of Amyloid versus F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia.

Ann Neurol 2021 02 7;89(2):389-401. Epub 2020 Dec 7.

Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem C-Pittsburgh compound B (PIB) and F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients.

Methods: One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information. PIB PET was rated as positive or negative for cortical retention, whereas FDG scans were read as showing an Alzheimer disease (AD) or non-AD pattern. Neuropathological diagnoses were assigned using research criteria. Majority visual reads were compared to intermediate-high AD neuropathological change (ADNC).

Results: One hundred one participants were included (mean age = 67.2 years, 41 females, Mini-Mental State Examination = 21.9, PET-to-autopsy interval = 4.4 years). At autopsy, 32 patients showed primary AD, 56 showed non-AD neuropathology (primarily frontotemporal lobar degeneration [FTLD]), and 13 showed mixed AD/FTLD pathology. PIB showed higher sensitivity than FDG for detecting intermediate-high ADNC (96%, 95% confidence interval [CI] = 89-100% vs 80%, 95% CI = 68-92%, p = 0.02), but equivalent specificity (86%, 95% CI = 76-95% vs 84%, 95% CI = 74-93%, p = 0.80). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% (95% CI = 92-100%) and specificity was 98% (95% CI = 93-100%). Nine of 24 patients with incongruent reads were found to have co-occurrence of AD and non-AD pathologies.

Interpretation: In our sample enriched for younger onset cognitive impairment, PIB-PET had higher sensitivity than FDG-PET for intermediate-high ADNC, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, whereas mixed pathology should be considered when PIB and FDG are incongruent. ANN NEUROL 2021;89:389-401.
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http://dx.doi.org/10.1002/ana.25968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856004PMC
February 2021

Long-Term Ambient Air Pollution Exposures and Brain Imaging Markers in Korean Adults: The Environmental Pollution-Induced Neurological EFfects (EPINEF) Study.

Environ Health Perspect 2020 11 20;128(11):117006. Epub 2020 Nov 20.

Institute of Human Complexity and Systems Science, Yonsei University, Incheon, Republic of Korea.

Background: Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide () and neuroimaging markers has been little studied in adults.

Objectives: We investigated the association between long-term exposure to air pollutants (, particulate matter (PM) with aerodynamic diameters of (PM10) and (PM2.5), and neuroimaging markers.

Methods: The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, , and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders.

Results: A increase in PM10 was associated with reduced thicknesses in the frontal [ (95% CI: , )] and temporal lobes [ (95% CI: , )]. A increase in PM2.5 was associated with a thinner temporal cortex [ (95% CI: , )]. A 10-ppb increase in was associated with reduced thicknesses in the global [ (95% CI: , 0.00)], frontal [ (95% CI: , )], parietal [ (95% CI: , )], temporal [ (95% CI: , )], and insular lobes [ (95% CI: , 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens.

Discussion: The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133.
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http://dx.doi.org/10.1289/EHP7133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678746PMC
November 2020

Cerebrospinal Fluid Biomarkers for the Diagnosis and Classification of Alzheimer's Disease Spectrum.

J Korean Med Sci 2020 Nov 16;35(44):e361. Epub 2020 Nov 16.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Cerebrospinal fluid (CSF) biomarkers are increasingly used in clinical practice for the diagnosis of Alzheimer's disease (AD). We aimed to 1) determine cutoff values of CSF biomarkers for AD, 2) investigate their clinical utility by estimating a concordance with amyloid positron emission tomography (PET), and 3) apply ATN (amyloid/tau/neurodegeneration) classification based on CSF results.

Methods: We performed CSF analysis in 51 normal controls (NC), 23 mild cognitive impairment (MCI) and 65 AD dementia (ADD) patients at the Samsung Medical Center in Korea. We attempted to develop cutoff of CSF biomarkers for differentiating ADD from NC using receiver operating characteristic analysis. We also investigated a concordance between CSF and amyloid PET results and applied ATN classification scheme based on CSF biomarker abnormalities to characterize our participants.

Results: CSF Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) significantly differed across the three groups. The area under curve for the differentiation between NC and ADD was highest in t-tau/Aβ42 (0.994) followed by p-tau/Aβ42 (0.963), Aβ42 (0.960), t-tau (0.918), and p-tau (0.684). The concordance rate between CSF Aβ42 and amyloid PET results was 92%. Finally, ATN classification based on CSF biomarker abnormalities led to a majority of NC categorized into A-T-N-(73%), MCI as A+T-N-(30%)/A+T+N+(26%), and ADD as A+T+N+(57%).

Conclusion: CSF biomarkers had high sensitivity and specificity in differentiating ADD from NC and were as accurate as amyloid PET. The ATN subtypes based on CSF biomarkers may further serve to predict the prognosis.
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http://dx.doi.org/10.3346/jkms.2020.35.e361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669457PMC
November 2020
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