Doh Kwan Kim

Clinical and angiographic follow-up of spontaneous isolated superior mesenteric artery dissection.

OBJECTIVES To observe the clinical features and angiographic findings in patients with a spontaneous isolated superior mesenteric artery dissection (SISMAD) and to identify any correlation between them. METHODS From a single institution, 32 patients (22 symptomatic patients at presentation; mean age 54years; men 97%) with SISMAD were retrospectively reviewed. All patients were available for clinical follow-up after treatment (conservative, n=28, 88%, open or endovascular superior mesenteric artery (SMA) reconstruction, n=4, 12%), and follow-up CT scans were available in 28 patients (mean 22months, range 1-80months). RESULTS We found a positive correlation between pain severity and dissection length (p=0.03, rho=0.50, Spearmans partial correlation analysis). After conservative treatment, only one patient (3%) required bowel resection, and there was no difference in outcome between patients who were treated with anticoagulation or anti-platelet therapy and those who were not (p=1.00, Fishers exact test). No patients had progression of their lesion on the follow-up CT angiography. CONCLUSIONS In SISMAD patients, dissection length is positively associated with more severe clinical symptoms. After conservative treatment, we observed a benign clinical course and no CT progression of the dissection, even without anticoagulation or anti-platelet therapy. Based on our observation, patients with SISMAD can be treated conservatively without anticoagulation therapy.

Serum melanotransferrin, p97 as a biochemical marker of Alzheimer's disease.

The protein melanotransferrin (p97) is associated with the brain lesions of Alzheimers disease (AD) and is a potential marker of the disorder. We measured serum p97 concentrations in 211 subjects: 71 patients with AD, 56 patients with non-AD-type dementia, and 84 normal control subjects. Serum p97 concentrations were elevated 3- to 4-fold in AD (median 15.00 pg/μl, interquartile range 10.20–17.00 pg/μl) as compared to non AD dementia (2.85 pg/μl, 1.93–7.15 pg/μl) and normal controls (3.20 pg/μl, 2.55–3.95 pg/μl). The mean elevation was significant at 13.54 ± 3.72 pg/μl, even in the 38 subjects with mild AD (CDR stage 0.5–1). Receiver operating characteristic analyses confirmed an optimal diagnostic threshold of 10.0 pg/μl, which yielded over-all accuracy of 0.882 to 0.915. Serum p97 is a candidate marker of AD, even in the early stage when clinical diagnosis is most uncertain.

Impairment of Instrumental Activities of Daily Living in Patients with Mild Cognitive Impairment

Objective This study was conducted to examine the following: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls. Methods This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning. Results The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%). Conclusion The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.

Predicting national suicide numbers with social media data

Suicide is not only an individual phenomenon, but it is also influenced by social and environmental factors. With the high suicide rate and the abundance of social media data in South Korea, we have studied the potential of this new medium for predicting completed suicide at the population level. We tested two social media variables (suicide-related and dysphoria-related weblog entries) along with classical social, economic and meteorological variables as predictors of suicide over 3 years (2008 through 2010). Both social media variables were powerfully associated with suicide frequency. The suicide variable displayed high variability and was reactive to celebrity suicide events, while the dysphoria variable showed longer secular trends, with lower variability. We interpret these as reflections of social affect and social mood, respectively. In the final multivariate model, the two social media variables, especially the dysphoria variable, displaced two classical economic predictors – consumer price index and unemployment rate. The prediction model developed with the 2-year training data set (2008 through 2009) was validated in the data for 2010 and was robust in a sensitivity analysis controlling for celebrity suicide effects. These results indicate that social media data may be of value in national suicide forecasting and prevention.

No association between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer's disease

Butyrylcholinesterase (BChE) as well as acetylcholinesterase has been suggested to be associated with Alzheimers disease (AD). Lehmann et al. [1997: Hum Mol Genet 6:1933-1936] recently reported the synergism between the gene for the K variant of BChE (BCHE-K) and the epsilon4 allele of apolipoprotein E (APOE epsilon4) in late-onset confirmed AD with Caucasian subjects. The authors found that the allelic frequency of BCHE-K was 0.17 in 74 subjects with late-onset histopathologically diagnosed AD, which was higher than the frequencies in elderly control subjects (0.09) and in other dementias (0.07-0.10). The association of BCHE-K with late-onset AD was limited to carriers of APOE epsilon4, giving odds ratios of confirmed late-onset AD of 6.9-12.8. In the present study, we report the BCHE-K allelic frequencies in late-onset AD cases and in age-matched controls of the Korean population, which were 0.22 and 0.17, respectively. We could not find any association between BCHE-K and AD regardless of APOE epsilon4 carrier status. However, APOE epsilon4 clearly showed higher frequency in AD (0.33) than in elderly controls (0.09), giving an odds ratio of 5.2 (95% confidence interval, 2.7-10.0). Our results do not support the conclusion that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon4 as a susceptibility gene for late-onset AD, at least in the Korean population.

Factors associated with caregiver burden in patients with Alzheimer's disease.

Objective Caregivers for patients with Alzheimers disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms. Methods A cross-sectional study was conducted in a sample comprised of 1,164 pairs of patients with AD and caregivers from the Clinical Research of Dementia of South Korea study cohorts. The cognitive function of each sub-domain, functional impairments, depressive symptoms, and caregiver burden were assessed using the dementia version of Seoul Neuropsychological Screening Battery (SNSB-D), Barthel Index for Daily Living Activities (ADL), Seoul-Instrumental Activities of Daily Living (S-IADL), the Clinical Dementia Rating Sum of Box (CDR-SB), the Global Deterioration Scale (GDS), the Korean version of the Neuropsychiatric Inventory (K-NPI), and the 15-item Geriatric Depression Scale. Results We found that higher severity (higher CDR-SB and GDS scores) and more functional impairment (lower ADL and higher S-IADL scores) were significantly associated with higher caregiver burden. In addition, depressive symptoms of patients (higher Geriatric Depression Scale scores) were associated with higher caregiver burden. Conclusion Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being.

Gender differences in risk factors for transition from mild cognitive impairment to Alzheimer’s disease: A CREDOS study

BACKGROUND Women are subject to a disproportionate burden from Alzheimers disease (AD) and sex differences exist in treatment response and prognosis of the disease. Yet gender-specific risk factors have not been widely studied. We aimed to investigate gender-specific risk factors for AD in subjects with mild cognitive impairment (MCI). METHODS Participants (n=294) with MCI were recruited from a nationwide, prospective cohort study of dementia and were followed for a median (range) of 13.8 (6.0-36.0) months. Sex-stratified associations of progression to AD with baseline characteristics were explored. RESULTS Seventy-four individuals (25.2%) developed incident dementia (67 AD) during follow-up. Significant risk factors for probable AD differed by sex. In men, the significant risk factors were severe periventricular white matter hyperintensities, and poorer global cognitive function. In women, older age, clinically significant depressive symptoms at baseline, and positive APOE ε4 alleles were the significant risk factors. CONCLUSIONS Risk factors for progression from MCI to probable AD differed in men and women. These results may translate to gender-specific preventative or therapeutic strategies for patients with MCI.

Hormone replacement therapy in postmenopausal women with Alzheimer’s disease: a randomized, prospective study

OBJECTIVE To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimers disease. DESIGN Six-month, randomized, open-label study. SETTING University hospital. PATIENT(S) Fifty-five women with mild to moderate Alzheimers disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). INTERVENTION(S) In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). MAIN OUTCOME MEASURE(S) Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). RESULT(S) Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in epsilon 4-negative patients. CONCLUSION(S) Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In epsilon 4-negative patients, tacrine is preferable for cognition and mood.

Genetic association of an apolipoprotein C-I (APOC1) gene polymorphism with late-onset Alzheimer's disease

Since a deletion/insertion polymorphism in the promoter region of the apolipoprotein C-I (APOC1) gene has been reported to be associated with late-onset Alzheimers disease (LOAD), we examined the hypothesis in a Korean population with 120 LOAD cases and 132 age-matched controls. The frequency of APOC1 insertion allele (H2) was significantly increased in LOAD than in controls, giving an odds ratio of 3.3 (95% CI 2.0-5.5, P<0.0001). Logistic regression analysis revealed that the interaction model between APOE epsilon4 and APOC1 H2 yielded larger odds ratio than other models including either APOE epsilon4 or APOC1 H2 alone. In addition, the association between APOC1 H2 and LOAD remained significant after adjustment of the effect of APOE epsilon4 (P=0.036). These results support previous observations that the APOC1 might be an additional susceptibility gene for LOAD.

Association between air pollution and suicide in South Korea: a nationwide study

Suggestive associations of suicide with air pollutant concentrations have been reported. Recognizing regional and temporal variability of pollutant concentrations and of suicide, we undertook a detailed meta-analysis of completed suicides in relation to 5 major pollutants over 6 years in the 16 administrative regions of the Republic of Korea, while also controlling for other established influences on suicide rates. Of the 5 major pollutants examined, ozone concentrations had a powerful association with suicide rate, extending back to 4 weeks. Over the range of 2 standard deviations (SD) around the annual mean ozone concentration, the adjusted suicide rate increased by an estimated 7.8% of the annual mean rate. Particulate matter pollution also had a significant effect, strongest with a 4-week lag, equivalent to 3.6% of the annual mean rate over the same 2 SD range that approximated the half of annual observed range. These results strongly suggest deleterious effects of ozone and particulate matter pollution on the major public health problem of suicide.