Kang Uk Lee

The Prevalence of Dementia in Older People in an Urban Population of Korea: The Seoul Study

OBJECTIVES: To estimate prevalence of dementia and its subtypes in older people in Seoul, a metropolitan area of Korea, and compare these findings with estimates reported for other populations.

Association between apolipoprotein E polymorphism and Alzheimer's disease in Koreans

We analyzed the aplolipoprotein E (APOE) genotypes of 110 probable AD patients and 226 cognitively normal controls in Koreans. The APOE epsilon4 allele was more prevalent in both early- and late-onset AD patients (P < 0.01) than in controls. The odds for the APOE epsilon4-heterozygous subjects were 2.7 (95% CI = 1.6-4.5), and those for the APOE epsilon4-homozygous subjects were 17.4 (95% CI = 2.0-147.3). But the odds were not uniform across age groups, and were higher in women than in men. Although the APOE epsilon2 allele frequency did not differ by diagnosis, the patients carrying an APOE epsilon2 allele showed delayed age-at-onset (P = 0.02). In conclusion, the APOE e4 allele increased the risk for AD in dose-dependent manner, and the APOE epsilon4-conferred AD risk was age- and sex-dependent in Koreans.

The Domain-Specific, Stage-Limited Impact of the Apolipoprotein E Epsilon-4 Allele on Cognitive Functions in Alzheimer’s Disease

To examine the impact of the APOE Ε4 allele on the cognitive functions of Alzheimer’s disease (AD) patients, we administered the eight neuropsychological tests from the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery to 118 Korean AD patients. The impact of the APOE Ε4 allele was significant in the Word List Recall Test (WLRT) and the Word List Recognition Test (WLRcT) only, and its impact was confined to the very mild AD (VMAD) patients (F = 7.65, d.f. = 2, p < 0.01 for WLRT; F = 3.27, d.f. = 2, p = 0.04 for WLRcT). In the VMAD group, the performance on the two tests of the APOE-Ε4-positive patients was poorer than that of the APOE-Ε4-negative patients. Our findings suggest that the impact of the APOE Ε4 allele on cognitive functions in AD may be domain specific and confined to the early stage of AD.

Association of alpha-2-macroglobulin deletion polymorphism with sporadic Alzheimer’s disease in Koreans

Alpha-2-macroglobulin (A2M) deletion polymorphism was recently reported to be associated with Alzheimers disease (AD) in a way comparable to apolipoprotein E (APOE) polymorphism in a family-based study. However, the association of A2M deletion polymorphism with AD has not been consistently replicated in successive case-controlled studies. In order to evaluate whether this A2M polymorphism is associated with AD in Koreans, we examined the frequencies of the A2M deletion (D) allele and D-bearing genotypes in a group of Koreans composed of 100 sporadic AD patients and 203 control subjects. The frequency of the deletion (D) allele (P=0.046) was significantly different between the total group of AD patients and the controls, although the frequency of the D-bearing genotypes did not attain significance (P=0.078). When the subjects were stratified according to age at onset, there was significant difference in the frequencies of the D allele (P=0.044) and D-bearing genotypes (P=0.041) between late-onset AD patients (> or =65 years) and the controls. However, no significant difference was observed between early-onset AD patients (<65 years) and the control group. Additionally, when we divided the late-onset AD and control subjects by APOE epsilon4 status, the difference of the A2M D allelic frequency was significant only in the APOE epsilon4 negative subjects (P=0.015). In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.

Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans.

We analyzed the transferrin (TF) and apolipoprotein E (APOE) genotypes of 164 probable Alzheimers disease (AD) patients and 239 cognitively normal elderly controls in Koreans. We failed to detect a significant difference in genotypic frequencies and allelic frequencies of the TF polymorphism between the AD group and control group (P>0.1 by Chi square test). The frequency of the TF C2 variant did not differ by the diagnosis when the APOE epsilon4-positive subjects and APOE epsilon4-negative subjects were analyzed separately (P>0.1 by Chi square test). The TF C2 variant did not influence the age-at-onset of AD independently or synergistically with the occurrence of the APOE epsilon4 allele (P>0.1 by ANOVA). The TF C2 variant did not confer a risk for AD in Koreans.

Korean version of the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K): Clinical and neuropsychological assessment batteries

A Korean version of the Consortium to Establish a Registry for Alzheimers Disease Assessment Packet (CERAD-K) was created. The English-American version of CERAD clinical and neuropsychological assessment batteries was translated into Korean, and the psychometrical properties of the cognitive tests in the CERAD-K were established. In the translation, including back-translation, the basic structures of all measures in the original CERAD batteries were maintained. The CERAD-K was administered in a standardized manner to 106 dementia patients (aged 70.4 +/- 8.1 years), including 78 Alzheimers disease (AD) patients, and 186 controls (aged 68.4 +/- 4.6 years) who were recruited from 3 university hospitals and 2 elderly welfare centers. The cognitive tests in the CERAD-K successfully differentiated controls from the dementia patients and from the AD patients. They also showed substantial interrater reliability and 1-month test-retest reliability. The CERAD-K is an equally reliable and valid equivalent for the English version of the CERAD clinical and neuropsychological assessment batteries.

The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer’s Disease

Objective We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. Methods Patients who met the criteria for probable Alzheimer’s disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student’s t-test. Results At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). Conclusion Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.