Jung Hie 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.

Neurocognitive Dysfunction Associated With Sleep Quality and Sleep Apnea in Patients With Mild Cognitive Impairment

OBJECTIVES Sleep apnea syndrome (SAS) is considered a risk factor for cognitive decline in the elderly. The specific neurocognitive decline has been suggested as a predictive factor for dementia in patients with mild cognitive impairment (MCI). The authors aim to illustrate the sleep characteristics related to the specific neurocognitive decline in the community-dwelling elderly including patients with MCI. DESIGN Cross-sectional. SETTINGS Center for sleep and chronobiology in Kangwon National University Hospital. PARTICIPANTS Thirty patients with MCI and 30 age- and sex-matched normal elderly subjects were selected. MEASUREMENTS The authors administered seven tests in the Korean version of the Consortium to Establish A Registry of Alzheimers Disease Neuropsychological battery and conducted nocturnal polysomnography. A p value below 0.05 was considered a statistical significance. RESULTS There was no significant difference in sleep parameters between the MCI and normal comparison (NC) groups. Sleep efficiency was positively correlated with Constructional Recall (CR) scores in both NC and MCI groups (r = 0.393 and 0.391, respectively). The amount of slow wave sleep (SWS) was also positively correlated with Boston naming test (BNT) scores in both groups (r = 0.392, 0.470, respectively). Stepwise multiple regression models showed that SWS and the apnea index were significant independent variables associated with the BNT score (Δβ = 0.43 and -0.34, respectively; adjusted R = 0.298) in the MCI group, and the amount of rapid eye movement sleep was a significant independent variable associated with the CR score (Δβ = 0.49; adjusted R = 0.217) in the NC group. CONCLUSIONS Our results show that poor sleep quality and greater severity of SAS were associated with impaired language function reflecting frontal-subcortical pathology in patients with MCI. This suggests that vulnerability to a specific brain damage associated with SAS could increase the risk for dementia.

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.

Total Scores of the CERAD Neuropsychological Assessment Battery: Validation for Mild Cognitive Impairment and Dementia Patients With Diverse Etiologies

OBJECTIVES This study aimed to validate the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer Disease neuropsychological battery (CERAD-NP) for a large elderly population including mild cognitive impairment (MCI) and dementia patients with various etiologic backgrounds. The authors also investigated whether the addition of frontal-executive function score can improve the discrimination accuracy of the total scores for dementia and MCI. DESIGN, SETTING, AND PARTICIPANTS One thousand three hundred thirty-six normal comparison (NC), 583 dementia (420 AD, 111 non-AD dementia, and 52 mixed AD with non-AD dementia), and 250 MCI (223 amnestic and 27 nonamnestic MCI) individuals living in the community were included (all aged 60 years and older). RESULTS Both TS-I and TS-II were highly correlated with other global cognitive and functional scales. Both total scores showed, though modest, superior NC versus MCI discrimination ability to Mini-Mental State Examination (MMSE). Their discrimination ability for NC versus dementia was excellent and significantly better, especially in discriminating very mild dementia, than MMSE. The addition of frontal-executive test score to TS-I or TS-II did not make a significant improvement in dementia or MCI discrimination ability. Both of them also showed higher test-retest and interrater reliability than MMSE or any individual neuropsychological tests in the CERAD-NP. CONCLUSION These results strongly support the validity and usefulness of CERAD total scores for early detection and progression monitoring of MCI and dementia in clinical and research settings.

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.

Nocturnal Hypoxemia and Periodic Limb Movement Predict Mortality in Patients on Maintenance Hemodialysis

BACKGROUND AND OBJECTIVES Sleep disorders, including sleep-disordered breathing and periodic limb movements during sleep, are associated with an increased risk for cardiovascular diseases, which are the leading causes of death in patients with ESRD. This study investigated the association between sleep disorders and mortality in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Thirty patients on maintenance hemodialysis, who were clinically stable for >2 months, underwent overnight polysomnography to evaluate sleep parameters. RESULTS All patients were followed for a median of 48 months (range: 14 to 62 months), and 14 of them died during the follow-up period. Among the sleep parameters, the percent of sleep time with arterial oxygen saturation <90% (T <90%), mean arterial oxygen saturation, and periodic limb movement index score were associated with significant increases in the risk of death. However, associations of the apnea-hypopnea index or oxygen desaturation index with mortality were NS. The hazard ratios (95% confidence intervals) for death per one SD increment in the log-transformed T <90% and periodic limb movement index score were 2.10 (1.06 to 4.15) and 2.48 (1.11 to 5.52), respectively, after adjusting for age. CONCLUSIONS We found that nocturnal hypoxemia and periodic limb movement during sleep, rather than apnea itself, were associated with an increased risk for death in patients with ESRD. However, conclusions from this study should be drawn with caution, because they are limited by the small sample size.

Dream-disturbed sleep in insomnia and narcolepsy.

Both patients with narcolepsy and insomnia frequently present clinically with nocturnal sleep disrupted by disturbing dreams. Polysomnographic correlates of these reports are unclear. In this study, 24 patients with psychophysiological insomnia and 16 patients with narcolepsy were compared on selected polysomnographic and self-reported typical dream characteristics. As a group, patients with narcolepsy showed more frightening, recurrent dreams and shorter rapid eye movement (REM) segments when compared with patients with insomnia. However, within the narcolepsy group, there were few correlations between typical dream characteristics and any measure of REM segment length or REM density. In the insomnia group, shorter REM segments and higher REM density were related to typically more vivid, frightening, and disrupted dreaming. We speculate that the mechanisms of disturbed dream recall may be different in insomnia and narcolepsy.

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.

Reliability and validity of the Korean version of Morningness–Eveningness Questionnaire in adults aged 20–39 years

Morningness–Eveningness (ME) can be defined by the difference in individual diurnal preference observed from general behavioral patterns including sleep habits. The Horne & Östberg Morningness–Eveningness Questionnaire (MEQ) has been used for classifying ME types. We examined the reliability of a Korean version of the MEQ (Korean MEQ) and verified its validity by comparing responses on the Korean MEQ to objectively-recorded sleep–wake rhythms. After translating and back translating the MEQ from English into Korean, we examined the internal consistency of 19 items of the Korean MEQ in 91 subjects, and the test–retest reliability in 21 subjects who took the Korean MEQ twice, 4 weeks apart. The Korean MEQ was then administered to 1022 young adult subjects. A subset of 46 morning, neither, and evening type subjects took part in a validation study in which their rest-activity timing was collected by actigraphy for 7 days. Cosinor analyses on these data were done to obtain the acrophase and amplitude of the sleep–wake rhythm. Cronbach’s alpha of the total scores from the Korean MEQ was 0.77, and the test–retest reliability intra-class correlation coefficient was 0.90 (p < 0.0001). There was a significant negative correlation between Korean MEQ score and reported sleep–wake timing among the entire cohort (p < 0.0001). There was a significant difference in bedtime and wake time (on both work and free days), and in the mean sleep–wake rhythm acrophase, between ME types (p < 0.01). In this study, the validity of the Korean MEQ was verified by illustrating the difference in acrophases of the sleep–wake rhythm between the ME types in young adults.

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.