Exposure to ambient fine particles and neuropsychiatric symptoms in cognitive disorder: A repeated measure analysis from the CREDOS (Clinical Research Center for Dementia of South Korea) study.

There is a growing concern that air pollution, especially those particles <2.5 µm (PM2.5), could increase the risk of cognitive impairment and mental disorders. However, the relationship between ambient PM2.5 and neuropsychiatric symptoms in people with cognitive impairment is still undetermined. This longitudinal study included 645 pairs of cognitively impaired subjects, who had not changed residence within Seoul, and their caregivers from the Clinical Research Center for Dementia of South Korea study cohort between September 2005 and June 2010 (1763 days). Neuropsychiatric symptoms were measured by the Korean version of the Neuropsychiatry Inventory, and caregiver burden was examined by the Neuropsychiatry Inventory Caregiver Distress Scale at the first and second visits at the outpatient clinic. District-specific PM2.5 concentrations were constructed over 1 month to 1 year prior to each visit. A log-linear regression using generalized estimating equations to account for repeated measures was used to assess the relationship between PM2.5 exposure and neuropsychiatric symptoms or caregiver burden. Aggravated neuropsychiatric symptoms were associated with exposure to high PM2.5 levels (adjusted percent change: 16.7% [95% confidence interval (CI), 5.0-29.7] per 8.3 µg/m3 increase in 1-month moving averages). Increased caregiver burden was associated with high PM2.5 exposures only in caregivers for patients with Alzheimer's disease (adjusted percent change: 29.0% [95% CI, 8.1-53.9] per 8.3 µg/m3 increase in 1-month moving averages). The present results indicate that PM2.5 exposure is associated with aggravated neuropsychiatric symptoms and increased caregiver burden in subjects with cognitive impairment. The findings in this study suggest that the role of air pollution deserves great consideration in the aging population with cognitive impairment.

Exposure to General Anesthesia and Risk of Dementia: A Nationwide Population-Based Cohort Study.

BACKGROUND: There is a growing concern that general anesthesia could increase the risk of dementia. However, the relationship between anesthesia and subsequent dementia is still undetermined. OBJECTIVE: To determine whether the risk of dementia increases after exposure to general anesthesia. METHODS: A population-based prospective cohort study analyzing the Korean National Health Insurance Service-National Sample Cohort database was conducted of all persons aged over 50 years (n = 219,423) from 1 January 2003 and 31 December 2013. RESULTS: 44,956 in the general anesthesia group and 174,469 in the control group were followed for 12 years. The risk of dementia associated with previous exposure to general anesthesia was increased after adjusting for all covariates such as gender, age, health care visit frequency, and co-morbidities (Hazard ratio = 1.285, 95% confidence interval = 1.262-1.384, time-varying Cox hazard model). In addition, the number of anesthetic agents administered, the number of exposures to general anesthesia, the cumulative exposure time, and the organ category involved in surgery were associated with risk of dementia. CONCLUSION: In light of the increasing societal burden of dementia, careful surveillance for dementia and prevention guidelines for patients after general anesthesia are needed.

Clinical epidemiology of long-term suicide risk in a nationwide population-based cohort study in South Korea.

We investigated the effects of a large range of clinical factors on the long-term risk of suicide in the general population of South Korea. We analyzed the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database in South Korea. A total of 300,232 individuals were followed for up to 12 years. We obtained information on demographic variables (age and sex), lifestyle variables (cigarette smoking, alcohol drinking and exercise), psychiatric and physical disorders, laboratory examination results and physical examination findings. We conducted a competing risk survival analysis to estimate the risk of completed suicide. 725 individuals (241/100,000) died by suicide in the follow-up period. After Bonferroni correction, we found a significant suicide risk associated with 6 variables: Parkinson's disease, depressive disorder, obsessive-compulsive disorder (inverted association), elevated serum aspartate aminotransferase levels, male gender and age. Before Bonferroni correction, variables such as cigarette smoking, heavy alcohol drinking, psychotic disorder, other psychiatric disorder, benzodiazepine use and higher fasting glucose showed some significant association. In addition, body mass index and height were inversely related to completed suicide before Bonferroni correction. However, only the 6 variables listed above were robust predictors of suicide in the fully adjusted analyses with multiple test correction. Common medical conditions had no clear influence on suicide. Diverse clinical factors influenced the long-term risk of completed suicide in this general population sample. Comprehensive assessment of these risk factors will facilitate more focused suicide surveillance measures.

Extrapyramidal Signs and Risk of Progression from Mild Cognitive Impairment to Dementia: A Clinical Research Center for Dementia of South Korea Study.

OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53-0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30-17.39, p<0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.

Occupational Attainment as Risk Factor for Progression from Mild Cognitive Impairment to Alzheimer's Disease: A CREDOS Study.

High occupational attainment has been known as a marker of cognitive reserve. Previous studies in the general population have shown that high occupational attainment is associated with reduced risk of Alzheimer's disease (AD). However, few studies have assessed the effect of occupational attainment on the clinical course of mild cognitive impairment (MCI). In this study, we evaluated whether individuals with high occupational attainment show more frequent progression from MCI to AD. Participants (n = 961) with MCI were recruited from a nationwide, hospital-based multi-center cohort, and were followed for up to 60 months (median: 17.64, interquartile range [12.36, 29.28]). We used Cox regression for competing risks to analyze the effect of occupational attainment on development of AD, treating dementia other than AD as a competing risk. Among the 961 individuals with MCI, a total of 280 (29.1%) converted to dementia during the follow-up period. The risk of progression to AD was higher in the individuals with high occupational attainment after controlling for potential confounders (hazard ratio = 1.83, 95% confidence interval = 1.25-2.69, p = 0.002). High occupational attainment in individuals with MCI is an independent risk factor for higher progression rate of MCI to AD. This result suggests that the protective effect of high occupational attainment against cognitive decline disappears in the MCI stage, and that careful assessment of occupational history can yield important clinical information for prognosis in individuals with MCI.

Extrapyramidal Signs and Cognitive Subdomains in Alzheimer Disease.

OBJECTIVE: Extrapyramidal signs (EPS), commonly observed in Alzheimer disease (AD), predict cognitive impairment and functional decline. This study investigated the association between EPS and five cognitive subdomains in a large number of participants with AD. DESIGN: Cross-sectional analyses of the nationwide Clinical Research of Dementia of South Korea (CREDOS) study, 2005-2012. SETTING: Multicenter clinical settings. PARTICIPANTS: 1,737 participants with AD drawn from the CREDOS study. MEASUREMENTS: The EPS group was defined by the presence of at least one EPS based on neurologic examination. We assessed five cognitive subdomains: attention, language, visuospatial function, memory, and frontal/executive function using the Seoul Neuropsychological Screening Battery-Dementia version. The associations of EPS with each cognitive subdomain were analyzed with a multiple linear regression model after controlling for confounding factors: sex, age, years of education, severity of dementia (Clinical Dementia Rating Sum of Boxes), and white matter hyperintensities. RESULTS: 164 AD participants (9.4%) had EPS. AD participants with EPS showed lower performance compared with those without EPS in two cognitive subdomains: attention and visuospatial function. The language, memory, and frontal/executive subdomains did not differ between the EPS-positive and the EPS-negative groups. In addition, we found a significant moderating relationship between EPS and deep white matter hyperintensities on visuospatial function score. CONCLUSIONS: EPS in AD are associated with severe cognitive impairment in attention and visuospatial function. Careful screening for EPS in patients with AD may assist in prediction of cognitive profile.

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.

Association between functional impairment, depression, and extrapyramidal signs in neuroleptic-free patients with Alzheimer disease.

BACKGROUND: Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms. METHODS: In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination. RESULTS: The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases (P < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group (P < .001, odds ratio = 1.90, 95% confidence interval, 1.45-2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group (P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (P = .04, regression coefficient = 0.89, and median regression). CONCLUSION: The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.