Seung Ho Ryu

Korean version of mini mental status examination for dementia screening and its' short form.

Objective We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its short form (SMMSE-DS). Methods We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its age- and education-specific optimal cutoff scores for dementia. Results The internal consistency obtained by Cronbachs coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects. Conclusion The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels.

Correlation between the Severity of Obstructive Sleep Apnea and Heart Rate Variability Indices

The risk of cardiovascular disease is known to be increased in obstructive sleep apnea syndrome (OSAS). Its mechanism can be explained by the observation that the sympathetic tone increases due to repetitive apneas accompanied by hypoxias and arousals during sleep. Heart rate variability (HRV) representing cardiac autonomic function is mediated by respiratory sinus arrhythmia, baroreflex-related fluctuation, and thermoregulation-related fluctuation. We evaluated the heart rate variability of OSAS patients during night to assess their relationship with the severity of the symptoms. We studied overnight polysomnographies of 59 male untreated OSAS patients with moderate to severe symptoms (mean age 45.4± 11.7 yr, apnea-hypopnea index [AHI]=43.2±23.4 events per hour, and AHI >15). Moderate (mean age 47.1±9.4 yr, AHI=15-30, n=22) and severe (mean age 44.5±12.9 yr, AHI >30, n=37) OSAS patients were compared for the indices derived from time and frequency domain analysis of HRV, AHI, oxygen desaturation event index (ODI), arousal index (ArI), and sleep parameters. As a result, the severe OSAS group showed higher mean powers of total frequency (TF) (p=0.012), very low frequency (VLF) (p= 0.038), and low frequency (LF) (p=0.002) than the moderate OSAS group. The LF/HF ratio (p=0.005) was higher in the severe group compared to that of the moderate group. On the time domain analysis, the HRV triangular index (p=0.026) of severe OSAS group was significantly higher. AHI was correlated best with the LF/HF ratio (rp=0.610, p<0.001) of all the HRV indices. According to the results, the frequency domain indices tended to reveal the difference between the groups better than time domain indices. Especially the LF/HF ratio was thought to be the most useful parameter to estimate the degree of AHI in OSAS patients.

Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene

This study investigated the possible effect of the –1438A/G single-nucleotide polymorphism in the promoter region of the serotonin 2A receptor (5-HTR2A) gene on major depressive disorder (MDD) in a Korean population. This polymorphism was analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a case-control design, which revealed a significant difference in the genotype distributions (χ2 = 10.78, d.f. = 2, p = 0.005). The frequency of the –1438G allele was also much higher in MDD patients than in normal controls (χ2 = 7.20, p = 0.007; OR = 1.52, 95% CI 1.12–2.06). We also found significantly more carriers of the G allele (GG+AG genotypes) in MDD patients than in normal controls (χ2 = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40–4.32). Our results support the hypothesis that the –1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population.

Association between norepinephrine transporter gene polymorphism and major depression.

Noradrenergic and serotonergic abnormalities have long been implicated in patients with major depression. The novel selective norepinephrine reuptake inhibitor reboxetine has been shown to be at least as effective as imipramine, desipramine and fluoxetine in the treatment of major depression. It is suggested that the dysfunction of the norepinephrine transporter (NET) may be related to major depression. Although the transcriptional activity related to the NET gene expression is little known, it may be a good candidate gene for major depression. Therefore, we investigated whether the T-182C polymorphism of the NET gene is associated with major depression in a Korean sample of 112 major depression patients compared with 136 healthy controls. We found a significantly lower frequency in TT genotype in patients with major depression than in normal controls when the genotypes of T-182C polymorphism were classified into two groups: TT group versus TC + CC group (p = 0.019). This result suggests that the T-182C polymorphism in the NET gene might be associated with major depression.

Association between the 5-HT6 receptor C267T polymorphism and response to antidepressant treatment in major depressive disorder

Abstractu2002 The purpose of the present study was to determine if a 5‐HT6 receptor polymorphism is associated with antidepressant treatment response in major depressive disorder (MDD). Ninety‐one patients with MDD, compared with 127 normal control subjects, were evaluated after an 8‐week treatment period. An association analysis revealed no differences in genotype and allele distribution between patients with MDD and normal control subjects. However, there were significant differences in the treatment response in some Hamilton Depression Rating Scale (HAM‐D) scores (sleep, activity, somatic anxiety, and total) between genotypes. Moreover, the heterozygote group (CT genotype) had significantly better treatment response than the homozygote group (CCu2003+u2003TT genotypes), especially in the somatic‐anxiety subcategory and the total score of HAM‐D. These findings imply that a 5‐HT6 receptor polymorphism (C267T) is associated with treatment response in MDD.

Increased plasma nitric oxide metabolites in suicide attempters.

Objective: To evaluate any correlation between plasma levels of nitric oxide metabolites (NOx) and suicide attempt. Method: Plasma NOx levels were measured in 53 patients who had recently attempted suicide, 58 nonsuicidal psychiatric patients, and 75 normal controls. The severity of suicidal behaviors was evaluated using Weisman and Worden’s Risk-Rescue Rating Scale. Results: Plasma NOx levels were significantly higher in suicidal patients than nonsuicidal psychiatric patients or normal control subjects (F = 11.029, d.f. = 2, 183, p < 0.001). Among the patients with a diagnosis of major depression, suicidal depressive patients had significantly higher plasma NOx levels than nonsuicidal depressive patients (t = –3.090, d.f. = 84, p = 0.003). Conclusion: Our study suggests that increased NO production in plasma is associated with suicide attempt, especially in depressive patients.

No association between the tryptophan hydroxylase gene polymorphism and major depressive disorders and antidepressant response in a Korean population.

The serotonergic neurotransmitter system has been implicated in major depressive disorder (MDD) and appears to be the target of a variety of antidepressants. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin biosynthesis, and selective serotonin re-uptake inhibitors exert their activity enhancing the general serotonergic tone. The goal of this study was to investigate whether the A218C polymorphism of the TPH gene is associated with MDD or antidepressant response. All patients were evaluated at the start and in the eighth week of using the 21-item Hamilton Depression Rating Scale. Genotyping was analyzed with polymerase chain reaction. There were no significant differences in genotypes and allele frequencies between the MDD patients (n=93) and the control group (n=127) and in the antidepressant response among TPH gene variants. Results suggest that the A218C polymorphism of the TPH gene does not play a major role in pathogenesis in MDD and does not serve as a modulator of antidepressant activity.

The relationship between visceral adiposity and cognitive performance in older adults

BACKGROUNDna direct association between visceral adiposity on abdominal computed tomography (CT) and cognitive performance has not been reported.nnnOBJECTIVESnto investigate the associations between total and regional adiposity measured with abdominal CT, and cognitive performance in elderly persons and to explore their modification by age.nnnDESIGNncross-sectional study.nnnSETTINGna health promotion centre of a tertiary university hospital.nnnSUBJECTSntwo-hundred and fifty individuals aged 60 years and above who underwent anthropometric measurements, abdominal CT and cognitive testing.nnnMETHODSnadiposity measures included body mass index (BMI), waist circumference and visceral and subcutaneous adiposity by abdominal CT. Poor cognitive performance was defined as Mini-Mental State Examination score being at or below 1 SD of age, sex and education-normative values.nnnRESULTSnin multivariate logistic regression analyses obesity [odds ratio (OR) 2.61, 95% confidence interval (CI)=1.21-6.01, P=0.015] and being in the top tertile of the visceral adiposity area (OR: 2.58, 95% CI=1.001-6.62, P=0.045) were associated with poor cognitive performance in subjects younger than 70 years, but not in those 70 years and older.nnnCONCLUSIONnhigh adiposity, particularly visceral adiposity, was associated with poor cognitive functioning in younger elderly persons.

Normative study of the category fluency test (CFT) from nationwide data on community-dwelling elderly in Korea

OBJECTIVESnWe determined the influence of demographic characteristics on the categorical verbal fluency and to provided its normative data for the community-dwelling elderly with diverse educational attainment.nnnMETHODSnWe administered the CFT using the animal category to 3025 (1420 men and 1605 women) non-demented community-dwelling Koreans aged 60-96 years who had educational levels ranging from 0 to 22 years.nnnRESULTSnAge and education were associated significantly with performance of CFT, with education showing the stronger association. Education accounted for 14.0% of CFT score variance and age accounted for 3.2%. However, gender did not influence performance of the test. We present normative data for CFT stratified by age (60-64, 65-69, 70-74, 75-79, 80-84, and ≥85 years) and education (0, 1-3, 4-6, 7-9, 10-12, and ≥13 years).nnnCONCLUSIONSnThe CFT norms should provide clinically useful data for evaluating elderly people and help improve the interpretation of verbal fluency tasks and allow for greater diagnostic accuracy for cognitive disorders such as Alzheimers disease (AD).

Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease: Methodology and Baseline Sample Characteristics

Objective The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimers disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimers disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. Methods All participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [11C]Pittsburgh compound B-positron emission tomography (PET), and [18F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitoring and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannually with the full KBASE assessment, including neuroimaging and laboratory tests. Results As of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants–291 cognitively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)–were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. Conclusion The KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.