Brain-derived Neurotrophic Factor Is Associated with Cognitive Impairment in Elderly Korean Individuals

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is widely expressed in the mammalian brain and acts to regulate neuronal survival and influence cognitive processes. The present study measured serum BDNF levels to investigate the associations of the BDNF Val66Met and 5-hydroxytryptamine transporter linked promoter region (5-HTTLPR) polymorphisms with cognitive function in elderly Korean individuals. METHODS: Over 60 years, a total of 834 subjects were recruited for the present study. The subjects were classified into groups based on the degree of cognitive impairment (age-associated cognitive decline, mild cognitive impairment, and Alzheimer's disease) and compared with normal controls in terms of a neuropsychological assessment and a clinical evaluation. RESULTS: Of the initial 834 study participants, 165 (59 controls and 106 subjects with cognitive impairments) completed the study. There was a significant increase in serum BDNF levels in subjects with cognitive impairments relative to the control group and the BDNF Val66Met polymorphism was significantly associated with cognitive function but not serum BDNF levels. The 5-HTTLPR polymorphism did not have any associations with cognitive impairment or serum BDNF levels. CONCLUSION: The present findings suggest that BDNF may play a role in the pathophysiology of cognitive impairment and the BDNF Val66Met polymorphism may be an important factor in the susceptibility to these age-related deficits.

Epigenetic Mechanisms of Early Adverse Experience in the Development of Depression / 대한정신약물학회지

Depression is a common mental illness with a high lifetime prevalence rate in the general population. However, the pathophysiology of depression is still poorly understood. Recent studies showed that environmental factors can affect gene expression by modifying epigenetic factors. Early life stress (ELS) is likely a risk factor of lifetime vulnerability to stress and development of depression. ELS or stressful lifetime can induce changes in gene expression through epigenetic mechanism, such as DNA methylation or histone modification. In this article, recent researches on the epigenetic mechanisms of depression will be discussed.

Efficacy of Venlafaxine Hydrochloride Extended Release for the Treatment of Perimenopausal Depressive Women with Vasomotor Symptoms: Open-Label Observation Study / 대한정신약물학회지

OBJECTIVE: During the transition to menopause, various symptoms including vasomotor symptoms and depressed mood lead to low quality of life. We investigated the effect of low-dose venlafaxine hydrochloride extended release on depressed mood and vasomotor symptoms of perimenopausal women. METHODS: 33 perimenopausal women fulfilling Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for a depressive episode were enrolled between January 2014 and May 2014. Subjects were prescribed 37.5 mg/day or 75 mg/day venlafaxine hydrochloride according to clinician's judgement, and the dosages were maintained for 8 weeks. Depressed mood and other psychological difficulties were evaluated by using Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), Clinical Global Impression-Severity. Climacteric symptoms including vasomotor symptoms were evaluated by using Greene Climacteric Scale (GCS). For statistical analysis, paired t-test was used. RESULTS: Significant decreases in HAMD, HAMA, GCS scores were observed after 2 weeks of treatment and the trends continued until the end of the study. The scores of HAMD significantly decreased, 28 of them reached remission (HAMD < or =7). The scores on vasomotor symptoms of GCS after 8 week treatment significantly decreased compared to baseline (13.1+/-5.0, p<0.01). CONCLUSION: These results suggest that venlafaxine hydrochloride is effective and tolerable treatment option for vasomotor symptoms and depressed mood in perimenopausal women. To validate our results, furthur studies with double-blind, placebo controlled will be needed.

Understanding the Molecular Biology in the Pathogenesis of Depression / 대한정신약물학회지

Depression is a common psychiatric illness with a high lifetime prevalence in the general population. Serious problem, such as suicide is commonly occurring in the patients with depression. Till now, the monoamine hypothesis has been the most popular theory of pathogenesis for depression. However, the more specific pathophysiology of depression and cellular molecular mechanism underlying action of commercial antidepressant has not been clearly defined. Several recent studies demonstrated that neural plasticity, epigenetic and mammalian target of rapamycin signaling are promising answers to the pathophysiology of depression. In this article, current understanding of biology and molecular mechanisms of depression and new research on the pathophysiology of depression will be discussed.

A Correlation between Neurocognitive Function and Serum Lipid Levels among the Korean Elderly / 신경정신의학

OBJECTIVES: In this study, we evaluated the correlation between neurocognitive function and serum lipids levels among Koreans over 60 years old. Also, we investigated the sociodemographic risk factors and vascular risk factors in Alzheimer's disease. METHODS: Six hundred fifty elderly persons participated in this study. We screened for cognitive impairment via the Mini-Mental Status Examination-Korean version (MMSE-KC) and evaluated 181 participants using the Consortium to Establish a Registry for Alzheimer's disease, Korean version (CERAD-K). For further classification, we employed the Clinical Dementia Rating Scale (CDRS) and DSM-IV diagnostic criteria. Participants having a CDRS score of 1 or more were diagnosed as having Alzheimer's disease. RESULTS: We diagnosed 38 participants as having Alzheimer's disease, 67 participants as having mild cognitive impairment, and 76 participants as having no cognitive impairment. There were significant differences among the groups with regard to age, education, history of diabetes mellitus medication, history of head trauma, history of CVA, and Hachinski ischemic score (p<0.05). The mild cognitive impairment group showed inverse correlations between triglyceride serum level and both total MMSE-KC score and Orientation in MMSE-KC (rs=-0.267, p=0.029 ; rs=-0.324, p=0.007). This group also showed inverse correlations between total cholesterol serum level and both total MMSE-KC score and Orientation in MMSE-KC (rs=-0.259, p=0.034 ; rs=-0.417, p=0.000) and an inverse correlation between low density lipoprotein serum level and Orientation in MMSE-KC (rs=-0.320, p=0.008). CONCLUSION: There were inverse correlations between some lipids' serum levels and cognitive functions in the mild cognitive impairment group.

Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia

OBJECTIVE: The primary purpose of this study was to investigate the differences in the serum brain-derived neurotrophic factor (BDNF) level between elderly Korean people over 65 years with and without dementia. METHODS: 171 individuals over 65 years were enrolled in this study. Screening for cognitive impairments was carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of the mean MMSE-KC score, and these were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease, Korean version (CERAD-K) and the Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS score of 1 or higher were classified as having Alzheimer's disease (AD), and subjects with a CDRS score of 0.5 were classified as having a mild cognitive impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging-associated cognitive decline (AACD). Serum BDNF levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The serum BDNF levels were significantly lower in the subjects with MCI and AD compared with the healthy controls (p<0.01). A significant correlation was found between the total MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant correlation was observed between the severity of MMSE-KC and the total GDS score. A significant difference was found in the total score of GDS between the AACD group and subjects with AD (p<0.05). CONCLUSION: This study suggested that BDNF might be involved in the pathophysiology of cognitive decline in elderly people.

Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia

OBJECTIVE: The primary purpose of this study was to investigate the differences in the serum brain-derived neurotrophic factor (BDNF) level between elderly Korean people over 65 years with and without dementia. METHODS: 171 individuals over 65 years were enrolled in this study. Screening for cognitive impairments was carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of the mean MMSE-KC score, and these were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease, Korean version (CERAD-K) and the Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS score of 1 or higher were classified as having Alzheimer's disease (AD), and subjects with a CDRS score of 0.5 were classified as having a mild cognitive impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging-associated cognitive decline (AACD). Serum BDNF levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The serum BDNF levels were significantly lower in the subjects with MCI and AD compared with the healthy controls (p<0.01). A significant correlation was found between the total MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant correlation was observed between the severity of MMSE-KC and the total GDS score. A significant difference was found in the total score of GDS between the AACD group and subjects with AD (p<0.05). CONCLUSION: This study suggested that BDNF might be involved in the pathophysiology of cognitive decline in elderly people.

A Correlation between Neurocognitive Impairments and Serum Lipid Levels among the Korean Elderly / 신경정신의학

OBJECTIVES: In this study, the authors evaluated the correlation between neurocognitive impairments and serum lipids levels among Korean elderly over the age of 65. METHODS: A total of 609 elderly individuals participated in this study. Screening for cognitive impairments were carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). There were 197 subjects above 1.5SD of MMSEKC and they were evaluated using the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease (AD)(CERAD-KC) and Geriatric Depression Scale (GDS-K). RESULTS: There was a correlation between old age/low levels of education and AD (p<0.05, p<0.01). There was an inverse correlation between the serum level of total cholesterol and the word list recognition test scores. The serum levels of LDL cholesterol were inversely correlated with the scores on the constructional praxis test, word list recall test and word list recognition test. Inverse correlations between the serum level of triglyceride and scores on the word list recall test and word list recognition test were also observed. CONCLUSION: There were inverse correlations between the serum levels of lipids and language/memory function in subjects with AD.

Prevalence of Alzheimer's Dementia and Its Risk Factors in Community-Dwelling Elderly Koreans

OBJECTIVE: We estimated the prevalence of Alzheimer's dementia (AD) and mild cognitive impairment (MCI) and their risk factors in an urban community setting, focusing especially on metabolic syndrome. METHODS: A two-phase investigation based on a door-to-door survey was performed. In Phase I, we administered the Korean version of the Mini-Mental State Examination (MMSE-KC) of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K). Assessment Packet and the Korean version of the Geriatric Depression Scales (GDS-K) to all 706 participants aged 65 years or older. In Phase II of the study, 175 persons underwent physical and neurological examinations according to the protocol of the CERAD-K clinical assessment battery [CERAD-K (C)] and the neuropsychological assessment battery [CERAD-K (N)]. We also examined the association between cognitive decline and metabolic syndrome. AD and MCI were defined using the DSM-IV-TR criteria and the Clinical Dementia Rating (CDR) scales. RESULTS: The mean age (+/-SD) of the subjects was 74.3+/-16.7 years and the ratio of males to females was 53.2 to 46.8. The prevalence of Alzheimer's dementia was 9.0%, while that of MCI was 32.9%. Old age and lower educational level had significant associations with cognitive decline in the elderly, but gender, years of alcohol intake or smoking, and metabolic syndrome were not associated with AD or MCI. CONCLUSION: In this study, metabolic syndrome was not associated with Alzheimer's AD or MCI. Information regarding an association between Alzheimer's dementia and metabolic syndrome in this study will be helpful in formulating future public health policy and prevention strategies in Korea.