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ABSTRACT: Background: There is still debate over the utility of carotid intima-media thickness (C-IMT) or carotid plaque in predicting future cardiovascular events and death. Additionally, the importance of plasma homocysteine levels was raised as a predictor of cardiovascular events and death. Methods: 1,391 subjects were recruited from the Ansan Geriatric cohort. We used B-mode carotid ultrasonography to assess C-IMT and plaque, measuring average maximal IMT and average mean IMT through 6-8 measurements of far-wall IMT in both common carotid arteries. We evaluated the presence of plaque in carotid segments. Multivariable Cox regression analysis was used to predict both cardiovascular and all-cause mortality. Results: During a mean follow-up of 62.4 ± 12.4 months, 71 subjects (5.12%) died and 23 (1.66%) died of cardiovascular causes. Multivariable Cox regression analysis found the predictors of cardiovascular mortality to be average maximal IMT (HR = 3.709; 95% CI: 1.202-11.446) and plasma homocysteine (HR = 1.057; 95% CI: 1.012-1.103). All-cause mortality was independently associated with C-IMT (average maximal and average mean IMT) and plasma homocysteine. Conclusions: C-IMT and plasma homocysteine levels were found to predict cardiovascular and all-cause mortality independently of the presence of carotid plaque and other cardiovascular risk factors.
European Neurology 04/2013; 70(1):1-5. · 1.81 Impact Factor
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ABSTRACT: A 29-year-old man presented with unilateral dull headache for 3 days, similar to previous headache, but with right hemiparesis; there was no antecedent infection or trauma. MRI showed left striatocapsular infarction without evidence of cardioembolism or vasculitis. Digital subtraction angiography demonstrated stenosis of the left middle cerebral artery (MCA) trunk Intramural hematoma suggests arterial dissection. The bulging intramural hematoma seen on T2* corresponded with an eccentric high signal rim on sagittal T1-weighted imaging, along the anterosuperior MCA wall at the arterial perforator origin The diagnosis was spontaneous MCA dissection.
Neurology 01/2013; 80(4):419. · 8.31 Impact Factor
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ABSTRACT: Headache is the most common symptom of cerebral venous thrombosis (CVT); however, the detailed underlying mechanisms and characteristics of headache in CVT have not been well described. Here, we report two cases of CVT whose primary and lasting presentation was orthostatic headache, suggestive of decreased intracranial pressure. Contrary to our expectations, the headaches were associated with elevated cerebrospinal fluid (CSF) pressure. Magnetic resonance imaging and magnetic resonance venography showed characteristic voiding defects consistent with CVT. We suggest that orthostatic headache can be developed in a condition of decreased intracranial CSF volume in both intracranial hypotensive and intracranial hypertensive states. In these cases, orthostatic headache in CVT might be caused by decreased intracranial CSF volume that leads to the inferior displacement of the brain and traction on pain-sensitive intracranial vessels, despite increased CSF pressure on measurement. CVT should be considered in the differential diagnosis when a patient complains of orthostatic headache.
Annals of Indian Academy of Neurology 01/2013; 16(1):85-7. · 0.93 Impact Factor
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Clinical neurology and neurosurgery 04/2012; · 1.30 Impact Factor
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ABSTRACT: Although the association between elevated C-reactive protein (CRP) level and long-term outcome after ischemic stroke is well known, the association between CRP and early neurologic deterioration (END) has not yet been thoroughly studied. We investigated the impact of CRP on END in patients with acute ischemic stroke. From a prospectively collected, multicenter stroke registry, 428 patients with acute ischemic stroke diagnosed within 24 hours of onset were enrolled in the study. Patients with hemorrhagic stroke, transient ischemic attack, and thrombolysis were excluded. END was defined as a >2-point increase in the National Institutes of Health Stroke Scale score within a 72-hour period. Data considered potentially associated with CRP level and the END were collected. END was observed in 47 patients. CRP level, time before arrival at the hospital, age, female sex, hematocrit, high-density lipoprotein (HDL) cholesterol level, hemoglobin A(1c) level, and internal carotid artery occlusion were significantly associated with END. On logistic regression analysis, CRP level, internal carotid artery occlusion, and HDL cholesterol proved to be independent variables. Our data suggest that CRP level at admission is significantly associated with END in acute ischemic stroke. HDL cholesterol and internal carotid artery occlusion are also associated with END.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 01/2012; 21(3):181-6.
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Jeong Lan Kim,
Joon Hyuk Park,
Bong Jo Kim,
Moon Doo Kim,
Shin-Kyum Kim,
Yeon Kyung Chi,
Tae Hui Kim,
Seok Woo Moon, Moon Ho Park,
Jae Nam Bae, [......],
Dong Woo Lee,
Seok Bum Lee,
Jung Jae Lee,
Chang-Uk Lee,
Sung Man Chang,
Ji Won Han,
Jin Hyeong Jhoo,
Changsu Han,
Maeng Je Cho,
Ki Woong Kim
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ABSTRACT: ABSTRACTBackground: The influences of demographics, culture, language, and environmental changes on Mini-Mental State Examination (MMSE) scores are considerable.Methods: Using a sample of 7452 healthy, community-dwelling elderly Koreans, aged 55 to 94 years, who participated in the four ongoing geriatric cohorts in Korea, we investigated demographic influences on MMSE scores and derived normative data for this population. Geropsychiatrists strictly excluded subjects with cognitive disorders according to the protocol of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) Clinical Assessment Battery (CERAD-K-C).Results: Education (standardized β = 0.463), age (standardized β = -0.303), and gender (standardized β = -0.057) had significant effects on MMSE scores (p < 0.001). The score of MMSE increase 0.379 point per 1-year education, decrease 0.188 per 1-year older, and decrease 0.491 in women compared to men. Education explained 30.4% of the scores' total variance, which was much larger than the variances explained by age (8.4%) or gender (0.3%). Accordingly, we present normative data for the MMSE stratified by education (0, 1-3, 4-6, 7-9, 10-12, and ≥ 13 years), age (60-69, 70-79, and 80-89 years), and gender.Conclusions: We provide contemporary education-, age-, and gender-stratified norms for the MMSE, derived from a large, community-dwelling elderly Korean population sample, which could be useful in evaluating individual MMSE scores.
International Psychogeriatrics 12/2011; · 2.24 Impact Factor
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ABSTRACT: BACE1, which cleaves the amyloid precursor protein, is the rate-limiting enzyme for β-amyloid peptide production, leading to the pathogenesis of Alzheimer's disease (AD). A high plasma level of homocysteine, acting as a potent methyltransferase inhibitor, is assumed to be a risk factor for AD onset. Using the demethylating drug 5-aza-2'-deoxycytidine (5-Aza), we tested whether and how BACE1 expression is regulated in mouse BV-2 microglial cells. 5-Aza increased both BACE1 mRNA and protein levels in a dose-dependent manner. Bisulfite-sequencing analysis revealed that two CpG sites at positions +298 and +351 in the 5'-untranslated region (5'-UTR) of the BACE1 gene were specifically demethylated in BV-2 cells treated with 5-Aza. In silico analysis showed that the +351 site is the STAT3/CTCF-binding site; the function of the +298 site has not been identified. To assess whether these two CpG sites play an important role in 5-Aza-induced transcriptional activation of BACE1, we constructed a BACE1 gene promoter including the 5'-UTR (-1136 to +500) fused to a CpG-free luciferase gene (pCpGL-BACE1) and its mutant pCpGL-BACE1-AA, which has substituted CG dinucleotides at the two CpG sites of pCpGL-BACE1 to AA. Promoter analysis showed a significant decrease (∼30%) in the activity of pCpGL-BACE1-AA compared with that of pCpGL-BACE1. Furthermore, in vitro methylation of these two reporter constructs showed a complete silencing of their promoter activities. Our data demonstrate that BACE1 gene expression is regulated by DNA methylation of at least two CpG sites at positions +298 and +351 in the 5'-UTR in BV-2 microglial cells.
Biochemical and Biophysical Research Communications 12/2011; 417(1):387-92. · 2.48 Impact Factor
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ABSTRACT: The aim of this study is to investigate possible associations between a set of single-nucleotide polymorphisms (SNPs) within 10 genes with Schizophrenia (SCZ) and response to antipsychotics in Korean in-patients treated with antipsychotics. Two hundred and twenty-one SCZ in-patients and 170 psychiatrically healthy controls were genotyped for 42 SNPs within ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. Rs10042486 within 5HTR1A was associated with both SCZ and clinical improvement on PANSS total scores as well as on PANSS positive and PANSS negative scores. The haplotype analyses focusing on the four, three and two blocks' haplotypes within 5HTR1A confirmed such findings as well. We did not observe any significant association between the remaining genetic variants under investigation in this study and clinical outcomes. Our preliminary findings suggest that rs10042486 within 5HTR1A promoter region could be associated with SCZ and with clinical improvement on PANSS total, positive and negative scores in Korean patients with SCZ. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.
Archiv f ur Psychiatrie und Nervenkrankheiten 11/2011; 262(3):199-205. · 2.75 Impact Factor
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ABSTRACT: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively.
One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures--including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively--were recorded.
rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement.
Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions.
Neuropsychobiology 11/2011; 65(1):1-11. · 2.67 Impact Factor
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ABSTRACT: Sensory tricks are clinical maneuvers that may partially relieve dystonic contractions. Any clinical maneuver that modulates afferent sensory and efferent motor pathways could be used as a sensory trick in patients with cervical dystonia. Although various sensory tricks have been described to reduce cervical dystonia, little is known about the exact mechanisms by which they operate. We report a case of cervical dystonia that was alleviated through the use of a visual-sensory trick. Our findings suggest that visual stimulation might be an effective sensory trick in cervical dystonia by compensating for a defective sensory system, or because visual pathways might be also affected by sensory interactions in cervical dystonia.
Neurological Sciences 11/2011; 33(3):665-7. · 1.32 Impact Factor
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ABSTRACT: The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with schizophrenia and whether they could predict clinical outcomes in Korean in-patients treated with antipsychotics. One hundred forty five patients with MD, 221 in-patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. No significant association was found with the diagnosis of schizophrenia. We observed an association between rs3813296 genotype and improvement on PANSS negative scores. Our findings provide no evidence for an association between SNPs within GRIA1, GRIA2 and GRIA4 under investigation and schizophrenia susceptibility, although rs3813296 (GRIA2) could be associated with improvement on PANSS negative scores. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.
Neuroscience Letters 11/2011; 506(1):170-4. · 2.11 Impact Factor
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ABSTRACT: The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.
Archiv f ur Psychiatrie und Nervenkrankheiten 11/2011; 262(4):305-11. · 2.75 Impact Factor
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ABSTRACT: The present study explored whether d-amino acid oxidase activator (DAOA) variants were associated with schizophrenia and whether they could predict the clinical outcomes of patients treated with various antipsychotics.
Two hundred and twenty-one (221) patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for seven DAOA single-nucleotide polymorphisms (SNPs) (rs3916966, rs3916967, rs2391191, rs3916968, rs7139958, rs9558571 and rs778293). We also administered baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), to patients with schizophrenia.
None of the SNPs under investigation was associated with the development of schizophrenia. However, the rs7139958 AA and rs9558571 TT as well as the rs7139958 A and rs9558571 T genotypes were associated with higher scores on the PANSS positive subscale among patients with schizophrenia, possibly reflecting their greater susceptibility to the development of more severe positive symptoms. No other allele, genotype, or haplotype under investigation was significantly associated with any of the clinical parameters, including clinical improvement, in patients with schizophrenia.
Our results suggested that rs7139958 and rs9558571 SNPs may be associated with more severe baseline positive symptoms in patients with schizophrenia. However, further research is needed to draw more definitive conclusions given the limitations of our study.
International Journal of Psychiatry in Clinical Practice 11/2011; 15(4):303-10. · 0.43 Impact Factor
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ABSTRACT: The present study aimed to investigate whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with bipolar disorder (BD) and they could predict clinical outcomes in in-patients with BD treated with mood stabilizers.
One hundred and thirty-two (132) patients with BD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures including Young Mania Rating Scale for patients with BD were recorded. Statistical significance was set at the 0.005 level in order to reduce the likelihood of false positive results.
We failed to show an evidence for a possible association of GRIA1, GRIA2 and GRIA4 with BD patients, in terms of influences on diagnosis and treatment outcomes, although this was the first study to explore the influence of such genes for bipolar disorder.
Our results suggest that 17 SNPs within GRIA1, GRIA2 and GRIA4 may not be associated with the development and treatment outcomes in BD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.
International Journal of Psychiatry in Clinical Practice 10/2011; 16(1):18-26. · 0.43 Impact Factor
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Nam Hoon Kim,
Hye Sook Kim,
Chai Ryoung Eun,
Ji A Seo,
Hyun Joo Cho,
Sin Gon Kim,
Kyung Mook Choi,
Sei Hyun Baik,
Dong Seop Choi, Moon Ho Park,
Changsu Han,
Nan Hee Kim
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ABSTRACT: To examine the relationship between depression and various components of body composition, including fat and muscle, in elderly Koreans.
A cross-sectional sample of a longitudinal cohort from the Ansan Geriatric (AGE) Study.
Elderly people living in urban area (Ansan City, South Korea).
Eight hundred thirty-six participants (378 male, 458 female) aged 60 and older were recruited from April 2006 to January 2008.
Depressive symptoms were examined using the Korean version of the 30-item Geriatric Depression Scale (KGDS). Participants taking antidepressant medications or with a KGDS score of 14 or greater were classified as having depression. Abdominal visceral fat area (VFA) and subcutaneous fat area were assessed using single-slice computed tomography, and appendicular skeletal muscle mass (ASM) and percentage body fat (%BF) were determined using whole-body dual-energy X-ray absorptiometry.
Elderly men with depression had a lower ASM than those without depression (P = .01) after adjusting for age, body weight, and height. In men, the risk of depression was lower with higher body mass index (BMI) (odds ratio (OR) per 1-standard deviation (SD) increase = 0.70, 95% confidence interval (CI) = 0.51-0.96) after adjusting for all confounding variables and higher ASM (OR per 1-SD increase = 0.49; 95% CI = 0.29-0.85) after controlling for age, height, and weight. Similarly, depression was negatively associated with BMI in women (OR per 1-SD increase = 0.73; 95% CI = 0.56-0.95). Waist circumference, %BF, and VFA were not consistently associated with depression in men or women.
Depression in elderly Koreans is associated with low body mass and sarcopenia, especially in men.
Journal of the American Geriatrics Society 10/2011; 59(11):2062-8. · 3.74 Impact Factor
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ABSTRACT: To find out whether healthy control (HC), amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) subjects exhibit region and frequency specific spectral power differences and whether the spectral power changes correlate with domain-specific cognitive function.
Forty-one AD, 38 aMCI, and 39 HC subjects underwent quantitative EEG and comprehensive neuropsychological tests. Repeated measures analysis of variance was performed to identify differences in EEG spectral power among the three groups by scalp region and EEG frequency. Correlations between region and frequency specific spectral powers and neuropsychological test scores were evaluated.
Temporal and parieto-occipital theta band powers were highest in AD. Whereas, parieto-occipital alpha and frontal and temporal beta 2 band powers were highest in HC and lowest in AD (p<0.05). Temporal and parieto-occipital theta powers negatively correlated with verbal and visuospatial memory recall, while parieto-occipital alpha and temporal beta 2 powers positively correlated with verbal memory recall (p<0.01).
Region and frequency specific oscillatory characteristics of EEG reflect domain-specific cognitive function in patients with aMCI and AD.
Region and frequency specific spectral powers have clinical implications as additional markers differentiating AD, aMCI, and HC.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2011; 122(11):2169-76. · 3.12 Impact Factor
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ABSTRACT: Background: Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD.Methods: We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML).Results: EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61–2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84–2.41), pvWML (OR 2.09–3.14), and dWML (OR 1.83–3.42).Conclusions: EPSs in AD are associated with selected vascular risk factors as well as WMLs.
International Psychogeriatrics 05/2011; 23(05):780 - 787. · 2.24 Impact Factor
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ABSTRACT: The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within the tryptophan hydroxylase 2 gene (TPH2) could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants, mood stabilizers and antipsychotics, respectively. One hundred forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for six TPH2 SNPs (rs4570625, rs10748185, rs11179027, rs1386498, rs4469933, and rs17110747). Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale and Positive and Negative Syndrome Scale, for patients with MD, BD and schizophrenia, respectively were recorded. None of the SNPs under investigation were associated with MD, BD and schizophrenia. However, in patients with MD, the rs4570625-rs10748185 G-A haplotype was significantly associated with higher endpoint MADRS severity, though not with response. Our results suggest that TPH2 variants neither have a major role in MD, BD and schizophrenia nor in response to treatments.
Psychiatry Research 03/2011; 189(1):26-32. · 2.52 Impact Factor
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Clinical neurology and neurosurgery 02/2011; 113(6):513-4. · 1.30 Impact Factor
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ABSTRACT: Screening tests that briefly measure early signs of cognitive dysfunction in Alzheimer's disease (AD) are lacking. We devised a new scale focused on early detecting cognitive dysfunction: the Attention Questionnaire Scale (AQS). We prospectively studied the AQS in 268 subjects with varying degrees of cognitive dysfunction and compared it with the Mini-Mental Status Examination (MMSE), digit span test, trail making test part B, letter cancellation test, Instrumental ADL, Geriatric Depression Scale, and Clinical Dementia Rating Scale. The internal consistency was excellent with the AQS (Cronbach's α = 0.945). There were significant differences in the overall AQS scores across varying degree of cognitive dysfunction (26.80 ± 3.43 in normal elderly, 20.78 ± 4.83 in patients with mild cognitive impairment (MCI), 19.01 ± 4.49 in early AD, 16.00 ± 5.03 in mild AD, and 12.02 ± 6.28 in moderate AD), and subjects with the early stage of cognitive dysfunction could be further distinguished using the AQS than MMSE. The area under the receiver operating characteristic curve was estimated to be 0.93 (95% confidence interval 0.89-0.97) in screening for normal elderly versus patients with MCI or various stages of AD. The AQS provides greater screening ability for early stage cognitive dysfunction, used not only as a screening tool but also an appropriate simple questionnaire.
Journal of Alzheimer's disease: JAD 02/2011; 24(2):393-402. · 3.74 Impact Factor
