Kang Joon Lee

Weight gain associated with the α2a-adrenergic receptor -1291 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 α2‐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 α2a‐adrenergic receptor −1291 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) (X2 = 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 α2a‐adrenergic receptor and weight gain in Korean schizophrenic patients receiving olanzapine treatment.

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

Abstract  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.

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

Neuroinflammation has been recognized as a feature of Alzheimers 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.

G-protein β3 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 β3 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/m2, 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 (χ2=0.037, p=0.98; χ2=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.

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.

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

Behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimers 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 Alzheimers 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 Alzheimers 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 Alzheimers disease.

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

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 Alzheimers 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.

RELATIONSHIP BETWEEN BODY COMPOSITION AND COGNITIVE FUNCTION: USING BIOELECTRICAL IMPEDANCE ANALYSIS

using validated neuropsychological tests. Data extraction and assessment of quality were performed by two independent reviewers and data were summarized using a narrative review. Results: Twelve studies met the inclusion criteria, with a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making comparisons difficult and precluded pooling of studies formeta-analysis. For methodological quality, n1⁄47 studies were allocated a low to moderate quality score (Jadad et al., 1996).Overall, it was evident that the findings were inconsistent across the studies and do not provide clear evidence to support the effect of diet on cognition in MCIpatients. Supplementationwith eitherVitaminEorGinkgoBiloba, hadno significant effect on progression fromMCI to dementia and/or AD. For cognitive function, there were some improvements in cognitive performance, particularly in the domain of memory, with the most consistent results shown by B vitamin, folic acid and cocoa flavonol supplementation. Furthermore, therewere indications that the use of neuroimaging and biomarker outcomemeasuresmayprovide amore sensitive approach to detect changes in cognitive function and dietary change in comparison to clinical tests.Conclusions:This systematic review highlighted that to date, there is insufficient clinical trial data on the effect of diet on cognitive outcomes in MCI patients. There is need for further well-designed RCTs, with standardised and robust measures of cognition to further explore the role of diet in cognitive decline.

PERIPHERAL LEVELS OF FIBRINOGEN AND C-REACTIVE PROTEIN IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT

cerebral microbleed load was assessed using susceptibility weighted MRI at 9.4 T, The level of amyloid deposits and inflammation were assessed by immunostaining. Results: Noscapinetreatment augmented hypoperfusion in arcAb mice compared to control-treated arcAbmice in the cortex but not in the hippocampus and thalamus. The noscapine treatment also ameliorated the compromised vascular reactivity in the cortex but not hippocampus, caudate nucleus or thalamus of arcAbmice. The number of cerebral microbleeds did not differ between noscapine-treated and controltreated arcAb mice. Conclusions: Treatment with noscapine mitigated functional cerebrovascular deficits in arcAb mouse model. Thus, the kinin-kallikrein system constitutes a potential therapeutic target in AD.

Incidence and course of depression in patients with Alzheimer’s disease

Objective Depressive symptoms are common in Alzheimers 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.