Seong Yoon Kim

Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. However, there have been no studies that specifically investigate the structural differences that support this classification. In an attempt to compare regional cortical thickness in two subtypes of aMCI, we aimed to map the distribution of cortical thinning using a surface based cortical analysis of magnetic resonance imaging. The cortical thickness across the entire brain was measured in 9 patients with S-aMCI, 22 patients with M-aMCI, and 61 normal healthy subjects. Differences in the patterns of cortical thinning between S-aMCI and M-aMCI were assessed using ANCOVA on a vertex-by-vertex basis, and statistical maps of differences in cortical thickness between the groups were constructed using a surface model. Relative to controls, S-aMCI patients showed cortical thinning in the left medial temporal lobe, and M-aMCI patients showed cortical thinning in the left medial temporal lobe, precuneus, and anterior and inferior basal temporal, insular, and temporal association cortices. When the two MCI groups were directly compared, M-aMCI patients showed cortical thinning in left precuneus. Our studies suggest that M-aMCI is a transitional state between S-aMCI and Alzheimers disease, and that the cortical thinning is evidence that the precuneus is responsible for the multiple cognitive impairments in M-aMCI.

Brain-derived neurotrophic factor Val/Met polymorphism and bipolar disorder. Association of the Met allele with suicidal behavior of bipolar patients.

Background/Aims: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. Methods: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. Results: Allelic distributions did not differ significantly between bipolar patients and controls (χ2 = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (χ2 = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7–14.7). Conclusions: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.

Clinical Characteristics of a Nationwide Hospital-based Registry of Mild-to-Moderate Alzheimer's Disease Patients in Korea: A CREDOS (Clinical Research Center for Dementia of South Korea) Study

With rapid population aging, the socioeconomic burden caused by dementia care is snowballing. Although a few community-based studies of Alzheimers disease (AD) have been performed in Korea, there has never been a nationwide hospital-based study thereof. We aimed to identify the demographics and clinical characteristics of mild-to-moderate AD patients from the Clinical Research Center for Dementia of Korea (CREDOS) registry. A total of 1,786 patients were consecutively included from September 2005 to June 2010. Each patient underwent comprehensive neurological examination, interview for caregivers, laboratory investigations, neuropsychological tests, and brain MRI. The mean age was 74.0 yr and the female percentage 67.0%. The mean period of education was 7.1 yr and the frequency of early-onset AD (< 65 yr old) was 18.8%. Among the vascular risk factors, hypertension (48.9%) and diabetes mellitus (22.3%) were the most frequent. The mean score of the Korean version of Mini-Mental State Examination (K-MMSE) was 19.2 and the mean sum of box scores of Clinical Dementia Rating (CDR-SB) 5.1. Based on the well-structured, nationwide, and hospital-based registry, this study provides the unique clinical characteristics of AD and emphasizes the importance of vascular factors in AD in Korea.

Transcatheter arterial chemoembolization vs. chemoinfusion for unresectable hepatocellular carcinoma in patients with major portal vein thrombosis.

Background  Transcatheter arterial chemoembolization (TACE) has been limited in palliative treatment of unresectable hepatocellular carcinoma (HCC) with major portal vein (PV) invasion due to the possibility of liver failure following embolization. Transcatheter arterial chemoinfusion (TACI) has been an option in such cases.

A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities.

The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.

Impact of white matter changes on activities of daily living in mild to moderate dementia.

The association between white matter changes and activities of daily living (ADL) in a large, well-defined cohort of patients with mild-to-moderate dementia (either Alzheimer’s disease or subcortical vascular dementia) were investigated. A total of 289 patients were divided into three groups (140 mild, 99 moderate, and 50 severe) depending on the degree of white matter changes as indicated on brain magnetic resonance image scans. Further, we analyzed the three groups’ performances on basic and instrumental ADL. The degree of white matter changes was associated with greater age, hypertension, previous history of stroke, higher Hachinski Ischemic Score, worse global cognitive and functional status, and an increased impairment of basic ADL and instrumental ADL. The increased impairment with regard to the severe group’s performance on both the basic and instrumental ADL remained significant after adjustment for age and hypertension. Tasks involving physical activities were most significant. This was the first study investigating the association between white matter changes and ADL in a large, well-defined dementia cohort. The present study suggests that severe white matter changes may be associated with higher impairment on both basic and instrumental ADL.

FcγRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients

The aim of this study was to determine the distribution of the FcgRIIa and FcgRIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients. Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for FcgRIIa 131 R/H and FcgRIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the FcgRIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three FcgRIIa genotypes between the SLE and the controls (P=0.002 for R =R131 vs R/H131 and H/H131, OR 2.5 (95% CI 1.4–4.5), but not in FcgRIIIa genotypes. FcgRIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P=0.034 for R131 vs H131, OR 1.4 (95% CI 1.03–1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with FcgRIIa-R/R131 and in FcgRIIa-R allele. In 300 SLE patients, high binding allele combination H131=V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131=F176 allele combination among four FcgRIIa/FcgRIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of FcgRIIa-R/R131 or R131-allele than male controls, but FcgRIIa or FcgRIIIa genotypes had no association with renal involvement in male SLE patients. FcgRIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anti-cardiolipin antibody (/) and anti-Ro antibody (/) than male SLE, and had earlier onset of first symptoms. There was no skewing in FcgRIIa or FcgRIIIa genotypes between female SLE and female controls, but FcgRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in FcgRIIa-R/R131 among three FcgRIIa genotypes, and serositis in FcgRIIIa-F/F176 among three FcgRIIIa genotypes. FcgRIIa-R131 homozygote was a major predisposing factor to the development of SLE and FcgRIIa-R131 homozygote and R131 allele were a predisposing factor, and H131=V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and FcgRIIa and FcgRIIIa showed somewhat different clinical associations between the genders.

A Structural Model of Stress, Motivation, and Academic Performance in Medical Students

Objective The purpose of the present study was 1) to identify factors that may influence academic stress in medical students and 2) to investigate the causal relationships among these variables with path analysis. Methods One hundred sixty medical students participated in the present study. Psychological parameters were assessed with the Medical Stress Scale, Minnesota Multiphasic Personality Inventory, Hamilton Depression Scale, Beck Depression Inventory, and Academic Motivation Scale. Linear regression and path analysis were used to examine the relationships among variables. Results Significant correlations were noted between several factors and Medical Stress scores. Specifically, Hamilton Depression Scale scores (β=0.26, p=0.03) and amotivation (β=0.20, p=0.01) and extrinsically identified regulation (β=0.27, p<0.01) response categories on the Academic Motivation Scale had independent and significant influences on Medical Stress Scale scores. A path analysis model indicated that stress, motivation, and academic performance formed a triangular feedback loop. Moreover, depression was associated with both stress and motivation, and personality was associated with motivation. Conclusion The triangular feedback-loop structure in the present study indicated that actions that promote motivation benefit from interventions against stress and depression. Moreover, stress management increases motivation in students. Therefore, strategies designed to reduce academic pressures in medical students should consider these factors. Additional studies should focus on the relationship between motivation and depression.

Effects of Medial Temporal Atrophy and White Matter Hyperintensities on the Cognitive Functions in Patients with Alzheimer’s Disease

Aims: We conducted this study to investigate the independent association of medial temporal atrophy (MTA) and white matter hyperintensities (WMH) with cognitive impairments of Alzheimer’s disease (AD) patients and the interaction between MTA and WMH. Methods: From 13 centers, a total of 216 AD patients were consecutively recruited and their MTA and WMH were visually rated. We evaluated the association of MTA and WMH with the various cognitive domains, and the interaction between MTA and WMH. Results: MTA independently correlated with scores of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), delayed recalls of the Seoul Verbal Learning Test (SVLT), the Boston Naming Test (BNT), and Word Fluency. WMH independently correlated with MMSE, CDR, Digit Span, and Stroop word reading, but not with delayed recall. There were interactions of WMH and MTA on CDR (p = 0.004), SVLT (p = 0.023), BNT (p = 0.002) and the semantic Word Fluency (p = 0.007). Conclusion: MTA and WMH independently affected cognitive deficits in AD patients, with somewhat different patterns where MTA was associated mostly with memory and language, while WMH were associated with attention and frontal executive functions. This study also showed interactions between MTA and WMH on some cognitive deficits and dementia severity, suggesting that they synergistically contribute to cognitive impairment in AD.

Validity of the telephone interview for cognitive status (TICS) and modified TICS (TICSm) for mild cognitive imparment (MCI) and dementia screening

This study aimed to validate the TICS and modified TICS (TICSm) in Korean elderly population and to compare MCI and dementia screening ability between TICS and TICSm. TICS and TICSm were administered to 70 cognitively normal (CN), 75 MCI, and 85 dementia subjects, with mini-mental state examination (MMSE) and other cognitive and functional measures. TICS and TICSm scores were highly correlated with other global cognitive and functional scores. The CN vs. dementia discrimination ability of both instruments was as excellent as that of MMSE (sensitivity/specificity at optimal cutoff: 87.1/90.1 for TICS; 88.2/90.0 for TICSm). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were far from perfect (sensitivity/specificity: 69.3/68.6 for TICS; 73.3/67.1 for TICSm). There was no significant difference in dementia or MCI screening accuracy between TICS and TICSm. Both of them also showed high test-retest reliability. Our findings indicate that TICS and TICSm are reliable and as valid as MMSE in regard of screening cognitively impaired elderly. In terms of the comparison between TICSm and TICS, however, TICSm has little advantage over TICS for screening dementia and even MCI, in spite of longer administration time and more efforts required.