Authors: Pyun, Jung-Min | Park, Young Ho | Kim, SangYun
Article Type: Research Article
Abstract: Background: Although thyroid dysfunction has been considered as a cause of reversible cognitive impairment, association between subclinical hypothyroidism and cognitive impairment is controversial. Objective: We compared cognitive profiles of patients in an euthyroid or subclinical hypothyroid (sHypo) state, as well as their disease progression from mild cognitive impairment (MCI) to dementia within 3 years. Methods: We included 2,181 patients in a euthyroid and 284 in a sHypo state over 60 years of age who underwent an extensive cognitive assessment at Seoul National University Bundang Hospital but were not prescribed levothyroxine, methimazole, carbimazole, or propylthiouracil. After propensity score matching for age, …sex, and education level, 1,118 patients in a euthyroid and 283 patients in a sHypo state were included. Attention, language, memory, visuocontructive, and executive functions were compared between the groups using Student’s t -test or the Mann-Whitney U test. To investigate the association between disease progression and subclinical hypothyroidism, a Cox regression analyses was performed in 379 patients with MCI. Patients with thyroid-stimulating hormone levels over 10 mlU/L was classified as the “sHypo10”, and hazard ratios for sHypo or sHypo10 were assessed. Results: There was no difference in attention, language, memory, visuoconstructive, and executive functions between the patient groups. Progression from MCI to dementia was not associated with sHypo or sHypo10. Conclusion: There was no difference in cognitive profile between euthyroid and sHypo patients, and no association between subclinical hypothyroidism and disease progression. This might suggest a clue of strategies regarding hormone therapy in subclinical hypothyroidism with cognitive impairment. Show more
Keywords: cognition, dementia, mild cognitive impairment, subclinical hypothyroidism
DOI: 10.3233/JAD-220302
Citation: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 757-762, 2022
Authors: Kang, Eun Kyoung | Baek, Min Jae | Kim, SangYun | Paik, Nam-Jong
Article Type: Research Article
Abstract: Purpose: Attention decline after stroke is common and hampers the rehabilitation process, and non-invasive transcranial direct current stimulation (tDCS) has the potential to elicit behavioral changes by modulating cortical excitability. The authors tested the hypothesis that a single session of non-invasive cortical stimulation with excitatory anodal tDCS applied to the left dorsolateral prefrontal cortex (DLPFC) can improve attention in stroke patients. Methods: Ten patients with post-stroke cognitive decline (MMSE ⩽ 25) and 10 age-matched healthy controls participated in this double blind, sham-controlled, crossover study involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA for …1 min) to the left DLPFC. Attention was measured using a computerized Go/No-Go test before and after intervention. Improvements in accuracy and speed after stimulation relative to baseline were compared for real and sham stimulations. Results: In healthy controls, no significant improvement in Go/No-Go test was observed after either real or sham stimulation. However, in stroke patients, tDCS led to a significant improvement in response accuracy at 1 hour post-stimulation relative to baseline, and this improvement was maintained until 3 hours post-stimulation (P< 0.05), whereas sham stimulation did not lead to a significant improvement in response accuracy (P> 0.05). Changes in reaction times were comparable for the two stimulations (P> 0.05). Conclusion: Non invasive anodal tDCS applied to the left DLPFC was found to improve attention versus sham stimulation in stroke patients, which suggests that non-invasive cortical intervention could potentially be used during rehabilitative training to improve attention. Show more
Keywords: Attention, cognition, stroke, cortical stimulation, tDCS
DOI: 10.3233/RNN-2009-0514
Citation: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 647-652, 2009
Authors: Pyun, Jung-Min | Kang, Min Ju | Youn, Young Chul | Park, Young Ho | Kim, SangYun
Article Type: Research Article
Abstract: Background: Although dementia with Lewy bodies (DLB) is a degenerative disease involving irreversible pathological changes and subsequent progressive cognitive decline, some patients have presented with improved cognitive function at follow-ups. Their clinical and neuropsychological characteristics and the factors influencing this improvement remain unclear. Objective: To investigate differences in clinical and neuropsychological characteristics between DLB patients with and without cognitive improvement at a one-year follow-up, and to identify predictive factors of cognitive improvement. Methods: This retrospective study included 60 DLB patients, 28 patients in the improved group, and 32 patients in the non-improved group. A multiple linear regression model was used …to compare changes in cognitive function test scores between groups over the course of one year. Binary logistic regression analysis was performed to determine the odds ratios (ORs) of depressive symptoms as a predictor for cognitive improvement. Results: The improved group showed significant increases in immediate and delayed verbal memory function in one year over the non-improved group. We also found that baseline depressive symptoms were associated with an increased probability of cognitive improvement (OR 1.234, CI 1.043– 1.460). Conclusion: Depressive symptoms at baseline were related to a higher probability of a cognitive improvement at one-year follow-up. In addition, immediate and delayed verbal memory function showed significant improvement during one year in improved patients compared to non-improved patients. Show more
Keywords: Cognitive improvement, dementia with Lewy bodies, depressive symptoms
DOI: 10.3233/JAD-190685
Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 899-905, 2019
Authors: Pyun, Jung-Min | Kang, Min Ju | Yun, Younghwa | Park, Young Ho | Kim, SangYun
Article Type: Research Article
Abstract: Background: Sundown syndrome (SS) in patients with Alzheimer’s disease (AD) is characterized by aggravation of behavioral problems at sunset. Disturbance of the circadian rhythm, a possible cause of SS, also facilitates amyloidopathy and reduces sleep quality. However, the associations of SS with amyloidopathy and sleep quality remain unclear. Objective: To investigate the prevalence of SS in patients with AD, the association between SS and APOE ɛ 4 carrier, representing an enhanced amyloid pathology, and the relationship between SS and sleep quality in AD. Methods: We included 104 patients with late-onset AD and known APOE genotype. All participants underwent a structured …interview via informant-based questionnaires to assess sleep quality and the presence of SS. Binary logistic regression analysis was performed to determine odds ratios (ORs) of APOE ɛ 4 carrier and parameters of sleep quality for SS. Results: The prevalence of SS in AD was 27.8% (n = 29). Patients with SS were significantly more likely to be APOE ɛ 4 carriers and to have rapid eye movement sleep behavior disorder (RBD) and a higher Clinical Dementia Rating (CDR) score compared to those without SS. In the multivariate regression analysis, APOE ɛ 4 carrier (OR 3.158, CI 1.022–9.758), RBD (OR 2.166, CI 1.073–4.371), and higher CDR score (OR 2.453, CI 1.084–5.550) were associated with an increased risk of SS. Conclusion: The prevalence of SS in patients with AD was 27.8%. The presence of the APOE ɛ 4 allele, RBD, and more severe dementia are associated with an increased risk of SS in AD. Show more
Keywords: Alzheimer’s disease, APOE, circadian rhythm, REM sleep behavior disorder, sundown syndrome
DOI: 10.3233/JAD-190032
Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 521-528, 2019
Authors: Han, Sang-Won | Park, Young Ho | Jang, Eun Sun | Nho, Kwangsik | Kim, SangYun
Article Type: Short Communication
Abstract: To investigate an association of serum liver enzymes with Alzheimer’s disease (AD) diagnosis and cognitive performance, we performed logistic and linear regression analyses in 781 patients with AD and 405 cognitively normal subjects. We found that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels had significant positive associations with cognitive performance and were significantly decreased in AD patients. The alkaline phosphatase level and AST to ALT ratio were significantly negatively associated with cognitive performance and were significantly increased in AD patients. This suggests that these liver enzymes might be implicated in the pathogenesis of AD.
Keywords: Alzheimer’s disease, cognition, liver enzymes, neuropsychological assessment
DOI: 10.3233/JAD-220343
Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1371-1376, 2022
Authors: Pyun, Jung-Min | Kang, Min Ju | Ryoo, Nayoung | Suh, Jeewon | Youn, Young Chul | Park, Young Ho | Kim, SangYun
Article Type: Review Article
Abstract: Amyloid-β (Aβ) is a key protein in Alzheimer’s disease (AD) in that its accumulation induces complex pathological changes. Although there has been extensive research on the metabolism of Aβ in AD, new compelling results have recently emerged. Historically, the production and clearance of Aβ have been thought to originate in the central nervous system (CNS). However, recent evidence suggests that the production and clearance of Aβ can also occur in the peripheral system, and that the peripherally driven Aβ migrates to the CNS and induces amyloidopathy with subsequent AD pathologic changes in the brain. This concept implies that AD is …not restricted to the CNS but is a systemic disease instead. As such, the development of blood-based biomarkers targeting Aβ is of great interest. Central and peripheral Aβ are both active contributors to the pathology of AD and interact bidirectionally. Measuring peripheral Aβ is not just observing the reflection of the residual Aβ removed from the CNS but also tracking the ongoing process of AD pathology. Additionally, blood-based biomarkers could be a more accessible tool in clinical and research settings. Through arduous research, several blood-based biomarker assays have demonstrated notable results. In this review, we describe the metabolism of Aβ and the amyloid-targeting blood-based biomarkers of AD. Show more
Keywords: Alzheimer’s disease, amyloid-targeting, amyloid metabolism, blood-based biomarkers
DOI: 10.3233/JAD-200104
Citation: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 685-696, 2020
Authors: Jang, Jae-Won | Park, So Young | Park, Young Ho | Baek, Min Jae | Lim, Jae-Sung | Youn, Young Chul | Kim, SangYun
Article Type: Research Article
Abstract: Background: Brain magnetic resonance imaging (MRI) shows cerebral structural changes. However, a unified comprehensive visual rating scale (CVRS) has seldom been studied. Thus, we combined brain atrophy and small vessel disease scales and used an MRI template as a CVRS. Objective: The aims of this study were to design a simple and reliable CVRS, validate it by investigating cerebral structural changes in clinical groups, and made comparison to the volumetric measurements. Methods: Elderly subjects (n = 260) with normal cognition (NC, n = 65), mild cognitive impairment (MCI, n = 101), or Alzheimer's disease (AD, n = 94) were evaluated …with brain MRI according to the CVRS of brain atrophy and small vessel disease. Validation of the CVRS with structural changes, neuropsychological tests, and volumetric analyses was performed. Results: The CVRS revealed a high intra-rater and inter-rater agreement and it reflected the structural changes of subjects with NC, MCI, and AD better than volumetric measures (CVRS-coronal: F = 13.5, p < 0.001; CVRS-axial: F = 19.9, p < 0.001). The area under the receiver operation curve (aROC) of the CVRS showed higher accuracy than volumetric analyses. (NC versus MCI aROC: CVRS-coronal, 0.777; CVRS-axial, 0.773; MCI versus AD aROC: CVRS-coronal, 0.680; CVRS-axial, 0.681). Conclusion: The CVRS can be used clinically to conveniently measure structural changes of brain. It reflected cerebral structural changes of clinical groups and correlated with the age better than volumetric measures. Show more
Keywords: Alzheimer's disease, mild cognitive impairment, visual rating scale
DOI: 10.3233/JAD-142088
Citation: Journal of Alzheimer's Disease, vol. 44, no. 3, pp. 1023-1034, 2015
Authors: Kim, Bo-Hyun | Choi, Yong-Ho | Yang, Jin-Ju | Kim, SangYun | Nho, Kwangsik | Lee, Jong-Min | for the Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by a heterogeneous distribution of pathological changes in the brain. Cortical thickness is one of the most sensitive imaging biomarkers for AD representing structural atrophy. The purpose of this study is to identify novel genes associated with cortical thickness. We measured the whole-brain mean cortical thickness from magnetic resonance imaging (MRI) scans in 919 subjects from the Alzheimer’s Disease Neuroimaging Initiative cohort, including 163 AD patients, 488 mild cognitive impairment patients, and 268 cognitively normal participants. Based on the single-nucleotide polymorphism (SNP)-based genome-wide association study, we performed gene-based association analysis for …mean cortical thickness. Furthermore, we performed expression quantitative trait loci, protein-protein interaction network, and pathway analysis to identify biologically functional information. We identified four genes (B4GALNT1 , RAB44 , LOC101927583 , and SLC26A10 ), two pathways (cyclin-dependent protein kinase holoenzyme complex and nuclear cyclin-dependent protein kinase holoenzyme complex), and one protein-protein interaction (B4GALNT1 and GALNT8 pair). These genes are involved in protein degradation, GTPase activity, neuronal loss, and apoptosis. The identified pathways are involved in the cellular processes and neuronal differentiation, which contribute to neuronal loss that is responsible for AD. Furthermore, the most significant SNP (rs12320537) in B4GALNT1 is associated with expression levels of B4GALNT1 in several brain regions. Thus, the identified genes and pathways provide deeper mechanistic insight into the molecular basis of brain atrophy in AD. Show more
Keywords: Alzheimer’s disease, brain, cortical thickness, gene-based association analysis, genome-wide association study, imaging genetics
DOI: 10.3233/JAD-191175
Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 531-545, 2020
Authors: Moon, Byungseung | Kim, Seongheon | Park, Young Ho | Lim, Jae-Sung | Youn, Young Chul | Kim, SangYun | Jang, Jae-Won | for the Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: Background: Depressive symptoms are prevalent in patients with mild cognitive impairment (MCI) and are considered to be a risk factor for progression to dementia. Objective: The purpose of this study was to evaluate whether depressive symptoms in MCI promote disease progression in a manner related to amyloid status, and to determine the relationship between depressive symptoms and longitudinal cerebral structural changes. Methods: Baseline data for 336 patients with MCI (75 with depression and 261 without) from the Alzheimer’s Disease Neuroimaging Initiative study were analyzed. All participants underwent comprehensive cognitive testing, volumetric magnetic resonance imaging (MRI), and [18 F]AV45 positron emission …tomography amyloid imaging. Depressive symptoms were measured using the Neuropsychiatric Inventory Questionnaire. A voxel-based morphometric analysis using volumetric brain MRI data was used to compare longitudinal structural changes related to depressive symptoms. Results: The conversion rate to dementia was different between patients with and without depression in amyloid-positive MCI (40.8% versus 19.7%, respectively; p = 0.006). Patients who were amyloid-positive at baseline also exhibited a greater degree of 2-year cognitive decline. Depression in amyloid-positive MCI was associated with longitudinal cortical atrophy in the left cingulate gyrus. Conclusion: Our study indicates that the presence of depressive symptoms in patients with amyloid-positive MCI is associated with higher progression to dementia and longitudinal cortical atrophy. Show more
Keywords: Alzheimer’s disease, depression, mild cognitive impairment
DOI: 10.3233/JAD-170225
Citation: Journal of Alzheimer's Disease, vol. 58, no. 4, pp. 1255-1264, 2017
Authors: Kim, Hang-Rai | Park, Young Ho | Jang, Jae-Won | Park, So Young | Wang, Min Jeong | Baek, Min Jae | Kim, Beom Joon | Ahn, Soyeon | Kim, SangYun
Article Type: Research Article
Abstract: Background: Although medial temporal atrophy (MTA) is a useful imaging marker of the progression to dementia in mild cognitive impairment (MCI), substantial numbers of MCI patients without MTA still progress to dementia. Objective: We investigated whether visual ratings of posterior atrophy (PA) on magnetic resonance imaging show independent predictive value for the progression to dementia in MCI patients. Methods: This was a retrospective cohort study of elderly patients who visited Seoul National University Bundang Hospital between 2004 and 2012. A total of 148 patients who were initially diagnosed with MCI were followed for up to 3 years (median 22 months) …to determine whether they progressed to dementia. We used 4-point and 5-point visual rating scales to assess PA and MTA, respectively. PA and MTA scores were dichotomized into normal (no atrophy) or abnormal (atrophy) in each patient. We performed a Cox regression analysis to examine the hazard ratios (HRs) of PA and MTA for the progression to dementia with adjustment for age, APOE ɛ 4 allele status, and baseline Mini-Mental State Examination score. Results: Among the study population, 47 patients progressed to dementia. Visual assessment of the MRI scans revealed that 67 patients (45.3%) showed PA, whereas 85 patients (57.3%) showed MTA. The HRs with 95% confidence intervals for PA and MTA were 2.516 (1.244–5.091) and 4.238 (1.680–10.687), respectively. The predictive values of visually assessed PA and MTA remained significant, independent of the covariates. Conclusion: Visual assessment of PA has independent predictive value for progression to dementia in MCI patients. Show more
Keywords: Atrophy, biomarker, disease progression, mild cognitive impairment
DOI: 10.3233/JAD-160339
Citation: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 137-146, 2017