Choline acetyltransferase 2384G>a polymorphism and the risk of Alzheimer disease.

The potential association between choline acetyltransferase (CHAT) polymorphism and the risk of Alzheimer disease (AD) has been controversial. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E (APOE) polymorphism in the development of AD in a well-powered elderly Korean sample. We analyzed CHAT 2384G>A polymorphism and APOE polymorphism among 736 Korean patients with probable AD and 1386 nondemented Korean controls. We tested the association between AD and CHAT genotype using a logistic regression model. In addition, we used generalized multifactor dimensionality reduction to investigate the interaction between CHAT and APOE with regard to the risk of AD. The CHAT A allele was associated with AD risk in a dose-dependent manner (odds ratio=1.40, 95% confidence interval=1.06-1.85, P=0.018 for heterozygotes; and odds ratio=3.92, 95% confidence interval=1.78-8.58, P=0.001 for homozygotes). The generalized multifactor dimensionality reduction approach identified a significant gene-gene interaction between CHAT and APOE (Balanced accuracy score=0.647, P=0.001). The CHAT A/A genotype was associated with earlier onset of AD (F=5.070, df=2, P=0.007). The CHAT A allele was associated with AD risk in a dose-dependent manner, and its interaction with the APOE ε4 allele was significant with regard to the development of AD. The CHAT A allele was also associated with earlier onset and possibly accelerated progression of AD.

Clinical characteristics of a nationwide hospital-based registry of mild-to-moderate Alzheimer's disease patients in Korea: a CREDOS (Clinical Research Center for Dementia of South Korea) study.

With rapid population aging, the socioeconomic burden caused by dementia care is snowballing. Although a few community-based studies of Alzheimer's disease (AD) have been performed in Korea, there has never been a nationwide hospital-based study thereof. We aimed to identify the demographics and clinical characteristics of mild-to-moderate AD patients from the Clinical Research Center for Dementia of Korea (CREDOS) registry. A total of 1,786 patients were consecutively included from September 2005 to June 2010. Each patient underwent comprehensive neurological examination, interview for caregivers, laboratory investigations, neuropsychological tests, and brain MRI. The mean age was 74.0 yr and the female percentage 67.0%. The mean period of education was 7.1 yr and the frequency of early-onset AD (< 65 yr old) was 18.8%. Among the vascular risk factors, hypertension (48.9%) and diabetes mellitus (22.3%) were the most frequent. The mean score of the Korean version of Mini-Mental State Examination (K-MMSE) was 19.2 and the mean sum of box scores of Clinical Dementia Rating (CDR-SB) 5.1. Based on the well-structured, nationwide, and hospital-based registry, this study provides the unique clinical characteristics of AD and emphasizes the importance of vascular factors in AD in Korea.

Mortality Risk after Diagnosis of Early-Onset Alzheimer's Disease versus Late-Onset Alzheimer's Disease: A Propensity Score Matching Analysis.

BACKGROUND/OBJECTIVE: We aimed to compare the risk of mortality in patients with early-onset Alzheimer's disease (EOAD) versus those with late-onset AD (LOAD) using a large number of study subjects. We applied propensity score matching (PSM) to minimize confounding biases in the comparison between EOAD and LOAD. METHODS: We obtained data from elderly Korean subjects with AD (n = 3,611) at baseline from the CREDOS cohort study, which was conducted from November 2005 to July 2013. We conducted PSM to reduce the bias due to confounding variables related to survival in patients with AD. The risks of mortality associated with EOAD and LOAD were evaluated by Cox proportional hazard analyses, controlling for relevant covariates. RESULTS: After propensity score matching, 312 subjects with EOAD and 624 subjects with LOAD were selected for further analysis. The Cox proportional hazard analysis showed that patients with EOAD are at a greater risk for mortality compared to those with LOAD (Hazard Ratio: 2.01, 95% CI: 1.01-4.00, p-value: 0.04) when controlling for the direct effect of aging on mortality. The results did not change after adjusting for age at diagnosis, general cognitive function, nutritional factor related to body mass index, and physical disability using activities of daily living. The results support the assumption that EOAD takes a more malignant course than LOAD. CONCLUSIONS: Our results provide support for the idea that EOAD takes a clinical course that is distinct from that of LOAD, especially as pertains to the risk of mortality.

MRI-defined versus clinically-defined vascular depression; comparison of prediction of functional disability in the elderly.

BACKGROUND: We compared the validity of models of subcortical ischemic depression (SID) and depression-executive dysfunction syndrome (DED) in predicting functional disability in the elderly. METHODS: We obtained data from elderly Korean subjects (n=1356) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A generalized estimating equation (GEE) model was constructed to measure functional disability using instrumental activity of daily living as a primary outcome. A risk factor of interest was SID and DED evaluated by a visual rating scale of deep white matter hyperintensity in MRI, Stroop test and Geriatric Depression Scale (GDS) score. Receiver-operating-characteristic plots and area under the curve (AUC) test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome. RESULTS: The mean (SD) follow-up duration of the participants was 1.7 (0.9) years. The GEE model showed that presence of SID at baseline predicted functional disability compared to non-depressed subjects (GDS score: Odds ratio [OR] 1.76; 95% CI 1.23, 2.53; p=0.002). The association was also statistically significant among the DED group (OR 1.48; 95% CI 1.15, 1.92; p=0.003). There were no significant differences in predicting functional disability (95% CI: -0.003 to 0.009, p=0.366) according to AUC differences between SID and DED. CONCLUSIONS: The results will be useful in evaluating the cardinal features of the vascular depression hypothesis in predicting functional disability.

Differential effects of white matter hyperintensity on geriatric depressive symptoms according to APOE-ε4 status.

BACKGROUND: We aimed to examine differential effects of WMH on progression of depressive symptoms according to APOE ε4 status in the elderly. METHODS: We obtained data from elderly Korean subjects (n=707) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A linear mixed model stratified according to APOE genotype (APOE ε4 carrier vs. non-carrier) was constructed using GDS score as a primary outcome and degree of overall, deep, periventricular WMH evaluated by a visual rating scale as a risk factor of interest. We also tested interaction between APOE ε4, WMH and time as predictors of clinical progression on GDS scores to examine the moderating effect of APOE ε4 allele on the relationship between degree of WMH and progression of geriatric depressive symptoms. RESULTS: The mean (SD) follow-up duration of the participants was 2.0 (0.8) years. Among APOE ε4 carriers, a severe degree of overall and deep WMH, but not periventricular WMH, predicted progression of geriatric depressive symptoms (overall WMH: coefficient=0.96, p=0.010; deep WMH: 0.87, p=0.016). There were significant interaction between APOE ε4, degree of WMH and time in predicting GDS increase (5df, F=2.28, p=0.046). LIMITATIONS: Only subjects seeking medical attention and with follow-up measurements were enrolled in this study. Specific location of WMH and use of antidepressant were uncontrolled. CONCLUSIONS: Considering biological markers such as degree of WMH and APOE ε4 status may be clinically relevant to predicting progression of geriatric depressive symptoms.