A 9-Year Comparison of Dementia Prevalence in Korea: Results of NaSDEK 2008 and 2017.

BACKGROUND: In many high-income Western countries, the prevalence of dementia had been reduced over the past decades. OBJECTIVE: We investigated whether the prevalence of all-cause dementia, Alzheimer's disease, vascular dementia, and mild cognitive impairment (MCI) had changed in Korea from 2008 to 2017. METHODS: Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2017 was conducted on representative elderly populations that were randomly sampled across South Korea. Both surveys employed a two-stage design (screening and diagnostic phases) and diagnosed dementia and MCI according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the consensus criteria from the International Working Group, respectively. The numbers of participants aged 65 years or older in the screening and diagnostic phases were 6,141 and 1,673 in the NaSDEK 2008 and 2,972 and 474 in the NaSDEK 2017, respectively. RESULTS: The age- and sex-standardized prevalence of all-cause dementia and Alzheimer's disease showed nonsignificant decrease (12.3% to 9.8%, odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.54-1.48 for all-cause dementia; 7.6% to 6.8%, OR [95% CI] = 0.91 [0.58-1.42] for Alzheimer's disease). Vascular dementia decreased in the young-old population aged less than 75 years (2.7% to 0.001%, OR [95% CI] = 0.04 [0.01-0.15]) and in women (1.9% to 0.5%, OR [95% CI] = 0.27 [0.10-0.72]) while MCI remained stable (25.3% to 26.2%, OR [95% CI] = 1.08 [0.67-1.73]). CONCLUSION: We found that the prevalence of dementia in Korea showed a nonsignificant decrease between 2008 and 2017.

The Behavioral Effects of Combination Therapy of Memantine and Acetylcholinesterase Inhibitors Compared with Acetylcholinesterase Inhibitors Alone in Patients with Moderate Alzheimer's Dementia: A Double-Blind Randomized Placebo-Controlled Trial.

OBJECTIVE: This study aimed to investigate treatment effects of combination therapy of memantine and acetylcholinesterase inhibitors (AchEIs) compared with AchEIs alone on behavioral and psychological symptoms of dementia (BPSD) in patients with moderate Alzheimer's dementia (AD). METHODS: This was a 12-week, double-blind, randomized, placebo-controlled trial. A total of 148 patients with moderate AD participated in this study. Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver input, Gottfries-Bråne-Steen Scale, and Zarit Burden Interview were used as assessment scales. RESULTS: There were no significant differences in age, sex, or education between AChEIs alone and combination groups. The combination group showed significantly more improvement of NPI-disinhibition score (0.76±2.15) than the AChEIs alone group (-0.14±1.71) after 12 weeks. CONCLUSION: Our findings suggest that the combination therapy of memantine and AchEIs might be a beneficial option for reducing disinhibition symptoms of patients with moderate AD compared with AchEIs alone. We believe that clinicians need to consider additional memantine treatment when patients with moderate AD complain disinhibition symptom. A larger clinical trial is needed to further determine the efficacy and advantages of such combination therapy of memantine and AchEIs for treating BPSD of patients with moderate AD.

The Association of Blood-Based Inflammatory Factors IL-1ß, TGF-ß and CRP with Cognitive Function in Alzheimer's Disease and Mild Cognitive Impairment.

OBJECTIVE: Many patients suffer from dementia in its most common form, Alzheimer's disease (AD). In this study, the levels of IL-1ß, TGF-ß and CRP, which are involved in the inflammatory response in Alzheimer's disease and its mild cognitive impairment (MCI), were measured and analyzed. METHODS: Seventy nine subjects participated in this study (mean age: 75.56 years, female: 54.3%, AD: 26, MCI: 28, normal: 25). The overall cognitive function of the subjects and the severity of the disease stage were assessed using the Mini-Mental State Examination (MMSE-K), the Clinical Dementia Rating (CDR), the Global Deterioration Scale (GDS) and the Geriatric Depression Scale-Korean (GDS-K). RESULTS: It was observed that patients with AD had significantly higher levels of IL-1ß and TGF-ß than the patients with MCI and normal controls. In addition, the MCI group showed a statistically significantly higher TGF-ß concentration than the normal group. CONCLUSION: These results suggest that IL-1ß and TGF-ß may be useful biological markers for patients with Alzheimer's disease.

Blue Monday Is Real for Suicide: A Case-Control Study of 188,601 Suicides.

Many studies have reported that suicides tend to occur on Mondays. However, owing to a lack of controls, conclusive findings on the potential effects of a day of the week on suicides have been lacking. We analyzed public data for causes of death from 1997 to 2015 in the Republic of Korea. Accidental death was used as a control group. The probability of suicide on each day of the week according to age group was calculated. A total of 377,204 deaths (188,601 suicides and 188,603 accidental deaths) were used. The frequency of suicide was highest on Monday and decreased throughout the week until Saturday. Accidental death was highest on Saturday and showed no variations according to weekday. For people in their teens and 20s, the probabilities of suicide on Monday were 9% and 10% higher, respectively, than those on Sunday. As age increased, the differences in suicide probability according to the day of the week were attenuated. The so-called Blue Monday effect is real, particularly for people in their teens and 20s. Suicide prevention strategies that aim to attenuate the burden and stress of Mondays should be planned.

Gender differences in behavioral and psychological symptoms of patients with Alzheimer's disease.

Behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease have a strong correlation with cognitive impairment and impairment in activities of daily living. Although recent studies have reported that gender may play a role in BPSD, this finding was not evident in several other studies. The present study classified patients with Alzheimer's disease into groups with mild and moderate dementia to examine the gender differences in BPSD in each group. We divided a total of 125 patients diagnosed with Alzheimer's disease according to the criteria of the fifth edition of the Diagnostic and Statistic Manual of Mental Disorders (DSM-5) into groups with mild and moderate dementia. Then we examined whether the groups showed differences in memory functions, activities of daily living, and BPSD depending on gender. Our results showed a significant gender difference in Depression/Dysphoria symptoms (BPSD) among the patients in the mild dementia group (t=-2.344, p<0.05), but there was no significant gender difference among the patients in the moderate dementia group. For both the mild and moderate dementia groups, there were no significant gender differences in memory functions and activities of daily living. The results of this study indicated that female patients with mild dementia are more vulnerable to depression than male patients. Future studies should more continuously examine a variety of factors that affect BPSD depending on the severity of Alzheimer's disease.

Incidence and Course of Depression in Patients with Alzheimer's Disease.

OBJECTIVE: Depressive symptoms are common in Alzheimer's disease (AD) and they might influence the course and prognosis of AD. Depression could appear anytime in the course of the disease, and could either last considerably long or disappear easily. This study is intended to investigate the occurrence of depression in the course of AD and the risk factors of incidence. METHODS: This study targeted 1,272 AD patients without depressive symptoms at the start of this study in Korea. A total of 775 subjects completed the study, and the occurrence of depression was assessed after 12 months. Demographic information of subjects was collected and cognitive functions, overall functions, and depression severity were assessed at the start of this study and after 12 months. RESULTS: Among the 775 subjects, 103 subjects (13.29%) developed depression 12 months later. The MMSE-KC scores showed significant changes in both groups that developed depression and did not. In the univariate analysis, significant differences in the incidence of depression were found in terms of gender, the administration of the antidepressant at the baseline, the SGDS-K score, and the GDS score. The multiple logistic regression analysis showed that the increase in the incidence of depression was associated with a female, in the increase in SGDS-K score and the GDS score. CONCLUSION: The incidence of depression in the subjects who completed the 12-month follow-up observation was 13.29%. Moreover, in the multivariate analysis, a female gender and the severity of dementia, including the overall functions, seemed associated with the occurrence of depression.

Serum tumour necrosis factor-α and interleukin-6 levels in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Neuroinflammation has been recognized as a feature of Alzheimer's disease (AD), and mild cognitive impairment (MCI) is believed to share several pathological features with AD. The aim of the present study was to compare serum cytokine levels between patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects. METHODS: Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the Department of Psychiatry of IIlsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained, and peripheral cytokine levels, specifically tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels, were measured for all subjects. RESULTS: After adjustment for age, a significant difference in IL-6 levels (P = 0.045), but not in TNF-α (P = 0.082) levels, was observed among the three groups. IL-6 levels were higher in patients with AD than in subjects with MCI and healthy controls. TNF-α and IL-6 levels negatively and positively correlated with Mini-Mental State Examination and Global Deterioration Scale scores, respectively. TNF-α and IL-6 levels were also positively correlated with each other. CONCLUSIONS: The present study suggests that serum IL-6 levels of patients with AD might be higher than those of subjects with MCI and healthy controls. Serum TNF-α and IL-6 levels might be negatively correlated with cognitive function, and we suspect that serum IL-6 levels could be biomarkers for AD.

Caregiver Preference and Treatment Compliance in Patients with Mild-to-Moderate Alzheimer's Disease in South Korea: RECAP Study Results.

INTRODUCTION: The aim of this study was to assess caregiver preference and treatment compliance with oral and transdermal medications in a "real-world" setting in patients with mild-to-moderate Alzheimer's disease (AD) in South Korea. METHODS: Real-world evaluation of compliance and preference in Alzheimer's disease treatment (RECAP) was a 24-week, multicenter, prospective, non-interventional study in patients with AD treated with oral or transdermal therapy. Here, we report data from patients living in South Korea. Eligible patients were grouped into one of two treatment cohorts: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). Caregiver preference, patient compliance, and physician preference were assessed at week 24 (end of the study). Safety was assessed by reported adverse events (AEs). RESULTS: A total of 398 patients were enrolled (oral 51.8%; transdermal 48.2%) and 79.4% completed the study. Caregivers of patients that were exposed to either the oral or transdermal monotherapy showed a preference for the treatment to which the patients were exposed (both p < 0.0001). However, caregivers of patients that were exposed to both forms of treatments reported a higher preference for transdermal monotherapy (65.9%; p < 0.0041). Patients in both treatment cohorts showed good compliance, with an overall mean (SD) score of 8.84 (1.514) (a median of 9). Of the 15 participating physicians, eight indicated their preference for transdermal therapy and seven preferred oral therapy at week 24. A total of 133 (33.4%) patients reported at least one AE during the study period (oral: 60 patients; transdermal: 73 patients). CONCLUSION: The study showed higher caregiver preference for transdermal monotherapy over oral monotherapy when patients with AD were exposed to both forms of treatment and good patient compliance for both oral and transdermal treatments.

Association of tripartite motif family-like 2 (TRIML2) polymorphisms with late-onset Alzheimer's disease risk in a Korean population.

Apoptosis is a prominent feature in the progression of Alzheimer's disease (AD), regulated in part by the activity of p53. As tripartite motif family-like 2 (TRIML2), a member of the TRIM family of proteins, has been implicated in the regulation of p53-mediated apoptosis, we hypothesized that TRIML2 polymorphisms may result in an increased AD susceptibility. Here, we investigated the association between coding region single nucleotide polymorphisms (cSNPs) in TRIML2 and AD in a Korean population. Two cSNPs (rs79698746 and rs2279551) were genotyped using the Sequenom iPLEX(®) Gold assay and direct sequencing in 162 AD patients and 191 controls. Multiple logistic regression models were used to determine the odds ratios, 95% confidence intervals, and p-values. Significant associations were observed between AD and the allelic frequencies of two SNPs (rs79698746, p=0.007; rs2279551, p=0.01); genotype frequencies were also significantly different between the two groups [rs79698746: p=0.003 in the codominant 2 model (CC vs. TT), p=0.01 in the dominant model (TC/CC vs. TT), p=0.016 in the recessive model (CC vs. TT/TC), and p=0.0025 in the log-additive model (TC vs. CC vs. TT); rs2279551: p=0.003 in the codominant 2 model (CC vs. TT), p=0.011 in the dominant model (TC/CC vs. TT), p=0.019 in the recessive model (CC vs. TT/TC), and p=0.0028 in the log-additive model (TC vs. CC vs. TT)]. In the haplotype analyses, CC haplotypes containing two cSNPs were significantly associated with AD (p=0.013). Taken together, these findings indicate that the C allele of both SNPs was associated with an increased risk of AD. These results suggest that TRIML2 may contribute to AD susceptibility.

Correlations between homocysteine and grey matter volume in patients with Alzheimer's disease.

BACKGROUND: Previous studies have reported that elevated total homocysteine levels are associated with cognitive dysfunction. However, few studies have examined the radiological markers of associated neuropathology in Alzheimer's disease (AD). We hypothesized that elevated levels of homocysteine are associated with cerebral grey matter volume loss. We compared the grey matter in a high homocysteine group and a normal homocysteine group using an optimized voxel-based morphometry. METHODS: The study included 79 patients with AD who were divided into two groups: a high homocysteine group and a normal homocysteine group. The participants underwent brain magnetic resonance imaging using a standardized protocol and neurocognitive evaluation. Homocysteine tests and other routine laboratory examinations for dementia assessment were carried out in all patients. RESULTS: There was no significant difference in grey matter volume between the patients with high homocysteine levels and those with normal homocysteine levels. A multiple regression analysis also revealed that the levels of homocysteine were not associated with the grey matter volume in patients with AD. Homocysteine levels were not correlated significantly with Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating. CONCLUSION: Our results showed that elevated homocysteine levels are not associated with reduced cerebral grey matter volume in AD. Larger samples will be needed to assess potential correlations between homocysteine and neuroanatomical pathology in the future.

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer's disease.

PURPOSE: Homocysteine has been associated with cognitive impairment and various psychiatric symptoms. This study was designed to clarify whether a relationship exists between the serum levels of homocysteine and the behavioral and psychological symptoms of dementia. METHODS: Patients with Alzheimer's disease (n=77) and control subjects (n=37) were included in this study. History taking, physical examination, and cognitive assessment were carried out as part of the investigation for the diagnosis of Alzheimer's disease based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Mini-Mental State Examination, Global Deterioration Scale, Clinical Dementia Rating, and the Korean version of the Neuropsychiatric Inventory were applied to all patients. The patients' serum homocysteine, folate, and vitamin B12 levels were measured. RESULTS: Patients with Alzheimer's disease had statistically significantly lower Mini-Mental State Examination scores and higher serum homocysteine levels compared to the control subjects. Mean serum folate and vitamin B12 concentration were significantly lower in patients with Alzheimer's disease compared to control subjects. A statistically significant positive correlation was found between the serum homocysteine levels and the Neuropsychiatric Inventory subdomains, including delusion, agitation/aggression, depression/dysphoria, elation/euphoria, apathy/indifference, and disinhibition. No statistically significant correlation was found between the serum homocysteine concentration and the Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating. CONCLUSION: Associations between the serum homocysteine levels and behavioral and psychological symptoms of dementia were observed, raising the possibility of an etiological role. However, the correlations between the folate or vitamin B12 levels and the Neuropsychiatric Inventory scores were not significant. The pathophysiological mechanisms underlying these findings remain to be elucidated. This was a cross-sectional study and the findings should be confirmed by repetitive, prospective longitudinal studies in a larger group of patients with neurodegenerative disorders.

Evidence-based, pharmacological treatment guideline for depression in Korea, revised edition.

This paper aims to introduce, summarize, and emphasize the importance of the 'Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition'. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.

Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis.

BACKGROUND: Numerous studies have reported that inflammation is closely associated with depression, and adjunctive non-steroidal anti-inflammatory drug (NSAID) treatment has been suggested as a novel therapeutic approach for depression. METHODS: We searched electronic databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials. We only included randomized controlled trials comparing adjunctive NSAIDs with placebos for treating depressive episodes. RESULTS: Of the 654 retrieved entries, we identified four relevant studies with a total of 150 patients (75 NSAID patients and 75 placebo patients) with depressive episodes. All four studies used celecoxib as the NSAID. The patients receiving adjunctive celecoxib had significantly higher mean changes in the Hamilton Rating Scale for Depression scores between baseline and endpoint measurements compared with those receiving placebo (weighted mean difference=3.26, 95% confidence interval; CI=1.81 to 4.71). The adjunctive celecoxib group also showed better remission (odds ratio; OR=6.58, 95% CI=2.55 to 17.00) and response rates (OR=6.49, 95% CI=2.89 to 14.55) than the placebo group. The all-cause drop-out rate was more favorable for the celecoxib group than for the placebo group (OR=0.45, 95% CI=0.18 to 1.13), although the statistical significance was not statistically significant (p=0.09). CONCLUSION: Adjunctive treatment with NSAIDs, particularly celecoxib, can be a promising strategy for patients with depressive disorder. Future studies with a larger sample size and longer study duration are needed to confirm the efficacy and tolerability of NSAIDs for depression.

G-protein beta3 Subunit Gene 825C/T Polymorphism Is Not Associated with Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients.

OBJECTIVE: Weight gain is a possible adverse effect of the use of antipsychotics, and is an important factor for long-term health and treatment compliance. Olanzapine is an atypical antipsychotic known to cause considerable weight gain. A relationship between weight gain and the G protein beta3 subunit gene (GNB3) 825C/T polymorphism has been reported. We therefore examined this possible association in a Korean schizophrenic patient group receiving olanzapine treatment. METHODS: Weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the 825C/T polymorphism was performed using a PCR-based method. RESULTS: We found that long-term treatment with olanzapine resulted in mean gains in weight and body mass index (BMI) of 5.2 kg and 1.93 kg/m(2), respectively. There was a no significant difference in the mean body weight change from baseline to the endpoint after olanzapine treatment between the genotype groups (p=0.796). There were also no significant differences in genotype or allele frequencies between the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%) groups (chi(2)=0.037, p=0.98; chi(2)=0.020, p=0.89). CONCLUSION: The finding from this study thus does not support a relationship between the GNB3 825C/T polymorphism and weight gain in Korean schizophrenic patients receiving olanzapine treatment.

Weight gain associated with the alpha2a-adrenergic receptor -1,291 C/G polymorphism and olanzapine treatment.

Weight gain can be an adverse effect of antipsychotics and is an important factor for long-term health and treatment compliance. Many reports have shown that the alpha(2)-adrenergic receptor may be related to eating behaviors or lipolytic activities, both associated with body weight change. We hypothesized that there might be a relationship between the alpha(2a)-adrenergic receptor -1,291 C/G polymorphism and olanzapine-induced weight gain. A group of 62 Korean schizophrenic patients participated in a study; weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the -1291 C/G polymorphism was performed on all participants. Body weight changes from baseline to endpoint were significantly associated with genotypes (P = 0.028). The frequency of the G allele was significantly higher in subjects who had severe weight gain (defined as a more than 10% weight gain from baseline) compared to subjects who did not have extreme weight gain (less than 10% weight gain from baseline) (X(2) = 6.120, P = 0.013; OR = 2.58, 95% CI = 1.21-5.51). Therefore, the findings from this study support a relationship between the -1291 C/G polymorphism of the alpha(2a)-adrenergic receptor and weight gain in Korean schizophrenic patients receiving olanzapine treatment.

Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations.

Electrophysiological studies have demonstrated gamma and beta frequency oscillations in response to auditory stimuli. The purpose of this study was to test whether auditory hallucinations (AH) in schizophrenia patients reflect abnormalities in gamma and beta frequency oscillations and to investigate source generators of these abnormalities. This theory was tested using quantitative electroencephalography (qEEG) and low-resolution electromagnetic tomography (LORETA) source imaging. Twenty-five schizophrenia patients with treatment refractory AH, lasting for at least 2 years, and 23 schizophrenia patients with non-AH (N-AH) in the past 2 years were recruited for the study. Spectral analysis of the qEEG and source imaging of frequency bands of artifact-free 30 s epochs were examined during rest. AH patients showed significantly increased beta 1 and beta 2 frequency amplitude compared with N-AH patients. Gamma and beta (2 and 3) frequencies were significantly correlated in AH but not in N-AH patients. Source imaging revealed significantly increased beta (1 and 2) activity in the left inferior parietal lobule and the left medial frontal gyrus in AH versus N-AH patients. These results imply that AH is reflecting increased beta frequency oscillations with neural generators localized in speech-related areas.

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

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 (CC + TT 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.