Prevalence of Dementia and Its Subtypes in an Elderly Urban Korean Population: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA)

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1 Original Research Article DOI: / Accepted: July 23, 2008 Published online: October 8, 2008 Prevalence of Dementia and Its Subtypes in an Elderly Urban Korean Population: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA) Jin Hyeong Jhoo a Ki Woong Kim b, c Yoonseok Huh b Seok Bum Lee f Joon Hyuk Park b Jung Jae Lee b Eun Ae Choi g Changsu Han d Il Han Choo e Jong Chul Youn h Dong Young Lee e Jong Inn Woo e a Department of Neuropsychiatry, Kangwon National University Hospital, Chunchon, b Department of Neuropsychiatry, Seoul National University Bundang Hospital, c Department of Psychiatry, Seoul National University College of Medicine, d Department of Psychiatry, Korea University College of Medicine and e Department of Neuropsychiatry, Seoul National University Hospital, Seoul, f Department of Psychiatry, Dankook University Hospital, Cheonan, g Department of Psychiatry, Gongju National Hospital, Gongju, and h Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Yongin, Korea Key Words Dementia, prevalence Alzheimer s disease Vascular dementia Dementia of Lewy body Korean population Abstract Background/Aims: We estimated the prevalence of dementia and its major subtypes in an elderly urban Korean population. Methods: A study population of 1,118 Korean elders was randomly sampled from the residents aged 65 years or older living in Seongnam, Korea. Standardized face-to-face interviews, and neurological and physical examinations were conducted on 714 respondents. Dementia was diagnosed according to the DSM-IV diagnostic criteria, and its subtypes were determined according to the criteria of the NINCDS-ADRDA, the NINDS-AIREN, and the consensus guideline proposed by McKeith et al. [Neurology 1996; 47: ]. Results: The estimated age- and gender-standardized prevalences were 6.3% for dementia (95% CI = ), 4.8% for Alzheimer s disease (AD; 95% CI = ), 1.0% for vascular dementia (VD; 95% CI = ), and 0.4% for dementia with Lewy bodies (DLB; 95% CI = ). The prevalence of AD consistently increased with age, whereas that of VD peaked at age years and decreased thereafter. Of the dementia patients, 72.0% were in the very mild or mild stages of the disease. Conclusions: The prevalence of dementia in a typical urban area of Korea was estimated to be 6.3%, and AD was the most prevalent subtype. DLB was less prevalent than VD among these community-dwelling Korean elders. Copyright 2008 S. Karger AG, Basel Introduction With the rapid increase of human longevity worldwide, dementia has become one of the most troubling global geriatric health problems. Over 18 million people worldwide are currently estimated to have dementia, and it is projected that 34 million people will be suffering Fax karger@karger.ch S. Karger AG, Basel /08/ $24.50/0 Accessible online at: Ki Woong Kim, MD, PhD Department of Neuropsychiatry Seoul National University Bundang Hospital 300 Gumidong, Bundanggu, Seongnam, Gyeonggido (Korea) Tel , Fax , kwkimmd@snu.ac.kr

2 from dementia in Of that number, over two thirds will be from developing countries in Asia and Latin America [1]. Two population-based epidemiological studies [2, 3] previously reported the prevalence of dementia to be 7.2 and 8.1% in urban Korean elderly populations. These rates were higher than those reported from urban populations of other Asian and western countries [1, 4 6]. The differences in these prevalence estimates of dementia may be due to different population characteristics or differences in study methodologies, such as case-finding procedures and the diagnostic threshold for dementia [7]. Furthermore, although the two previous studies on the prevalence of dementia in urban Korean elders were conducted in the two largest metropolitan cities of Korea (Seoul [3] and Busan [2] ), the study populations were not representative of the typical urban elderly population in Korea. In particular, the level of educational attainment, one of major sources of variation in dementia prevalence, was much lower in the studied samples than among Korean urban elders in general [2, 3, 8]. In Korean elders, the prevalence of Alzheimer s disease (AD) and vascular dementia (VD) has been estimated to range from 4.2 to 6.5% and 1.3 to 2.5%, respectively [3, 9 11]. However, although dementia with Lewy bodies (DLB) has been suggested to be the second most common type of degenerative dementia in older people [12], the prevalence of DLB has never been investigated in Korea. In previous population-based studies, prevalence of DLB was estimated to be much lower than that in a nonpopulation-based sample [12 15]. Methodologically, all the previous studies on dementia prevalence in Korea employed a two-phase design and used only the Mini-Mental State Examination (MMSE) [16] for screening dementia in the first phase, meaning that DLB was less likely to be detected than AD or VD since memory and language impairments are not prominent in the early stage of DLB [17]. Therefore, we herein employed a single-phase design and estimated the prevalence of dementia and its major subtypes including DLB in an urban elderly population of Korea. M e t h o d s Subjects This study was part of the Korean Longitudinal Study on Health and Aging (KLoSHA) [18] conducted between September 2005 and August 2006 on residents of Seongnam, Korea. Seongnam, one of the largest suburbs of Seoul, had a total population of 931,019 on August 1, 2005, including 61,730 (6.6%) individuals aged 65 years or older. A simple random sample (n = 1,118) was drawn from the roster of elderly individuals, and letters and telephone calls were used to invite these subjects to participate in our study. The mean subject age was years (range years), and 405 (36.2%) of the subjects were men. All subjects were Korean. Our study included only noninstitutionalized individuals. All subjects were fully informed of the study protocol and provided written statements of informed consent that were signed by themselves or their legal guardians. A s s e s s m e n t s All respondents were required to visit the Seoul National University Bundang Hospital (SNUBH), Seongnam, Korea for laboratory tests, face-to-face comprehensive interviews, and physical and neurological examinations. The respondents who could not visit the SNUBH undertook all of the assessments at home except for the body fat analysis and radiological exams. Standardized clinical interviews, neurological examination, and physical examination were conducted to diagnose comorbid cognitive disorders and cerebrovascular disorders. These were administered by four neuropsychiatrists according to the Korean version of the CERAD clinical assessment battery (CERAD- K) [19] and the transient ischemic attack (TIA)/stroke form from the Atherosclerosis Risk in Communities Study (ARIC) [20]. Comorbid major psychiatric disorders were assessed by three geropsychiatrists using the Mini International Neuropsychiatric Interview (MINI) [21]. Comprehensive neuropsychological assessments, including the Korean version of the CERAD neuropsychological assessment battery [22], frontal assessment battery [23], and digit span test [24], were also administered by four neuropsychologists. All respondents underwent routine blood examinations, urinalysis, electrocardiogram, and Doppler ultrasonography with spectral analysis of the large extracranial vessels. The respondents who were suspected to have dementia or stroke by the CERAD-K clinical assessment battery underwent brain magnetic resonance imaging or computed tomography. D i a g n o s i s Final diagnoses and the clinical dementia rating (CDR) index [25] were determined by the four geropsychiatrists. Dementia was first defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria [26]. AD was diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer s Disease and Related Disorders Association (NINCDS-ADRDA) [27], and VD was diagnosed according to the criteria of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l Enseignement en Neurosciences (NINDS-AIREN) [28]. DLB was diagnosed according to the consensus guideline proposed by McKeith et al. [29]. Both probable and possible cases were classified as dementia. Statistical Analyses The prevalences of AD, VD and overall dementia were calculated, stratified by gender (men and women) and age (65 69, 70 74, 75 79, 80 years old or over). Ninety-five percent confidence intervals (CIs) for each prevalence estimate were derived using the Prevalence of Dementia in Korean Elders 271

3 exact methods for a binomial parameter. The estimates of prevalence were adjusted by age and gender with regard to the population aged 65 and over in the Seongnam district, in order to estimate the overall prevalence rates in the district. Standardized prevalence rates for Korean elders were also estimated using the direct standardization method, in which the prevalence rates Table 1. Sociodemographic characteristics of subjects Men Women Total Total 301 (100.0) 413 (100.0) 714 (100.0) Age years 138 (45.8) 169 (40.9) 307 (43.0) years 100 (33.2) 117 (28.3) 217 (30.4) years 42 (14.0) 76 (18.4) 118 (16.5) 80 years 21 (7.0) 51 (12.3) 72 (10.1) Education 0 years 17 (5.6) 131 (31.7) 148 (20.7) 1 6 years 67 (22.3) 147 (35.6) 214 (30.0) 7 years 217 (72.1) 135 (32.7) 352 (49.3) Marriage Married 264 (87.7) 162 (39.2) 426 (59.7) Never married/ divorced/bereaved 37 (12.3) 251 (60.8) 288 (40.3) Income >12,000 USD/year 141 (46.8) 130 (31.5) 271 (38.0) 12,000 USD/year 160 (53.2) 283 (68.5) 443 (62.0) were adjusted by age and gender to the total Korean population, as given in the 2005 national census. The age-standardized prevalence of dementia according to the CDR index was reestimated using the same method, allowing us to compare our findings with those of other studies in which prevalence estimates were reported according to dementia severity. Logistic regression analyses were performed in order to evaluate the influence of age, gender, and education on the risk of dementia. All statistical analyses were performed using the SPSS 15.0 statistical software package. R e s u l t s A total of 714 subjects agreed to participate in the study (response rate = 63.9%). Table 1 shows the demographic characteristics of the KLoSHA population. The mean subject age was years and the percentage of women was 57.8%. The respondents were younger (quartile 1 = 67 years old, median = 71 years old; quartile 3 = 76 years old, 2 = , d.f. = 1, p! 0.001, Kruskal- Wallis test) and included fewer women (women = 70.8%, p! 0.01, 2 test) than the nonrespondents. Of the 714 participants, 28 were diagnosed as AD (24 women and 4 men), 7 as VD (4 women and 3 men), and 2 as DLB (both women). The crude prevalence of dementia was 5.2% (95% CI = %), and those of AD, VD Table 2. Prevalence estimates 1 of dementia in Korean elders Prevalence (95% CI) AD VD dementia Age years (n = 307) 1.3 ( ) 0.7 (0 1.6) 2.0 ( ) years (n = 217) 1.4 (0 2.9) 0.9 (0 2.2) 2.3 ( ) years (n = 118) 5.1 ( ) 1.7 (0 4.0) 8.5 ( ) 80 years (n = 72) 18.1 ( ) 1.4 (0 4.1) 22.2 ( ) Gender Men (n = 301) 1.5 ( ) 1.0 (0 2.2) 2.6 ( ) Women (n = 413) 7.0 ( ) 1.0 ( ) 8.8 ( ) Education 0 6 years (n = 362) 6.0 ( ) 0.8 (0 1.7) 7.6 ( ) 7 years (n = 352) 2.4 ( ) 1.0 (0 2.1) 3.5 ( ) All, crude 3.9 ( ) 1.0 ( ) 5.2 ( ) All, adjusted ( ) 1.0 ( ) 6.2 ( ) Age-standardized ( ) 1.0 ( ) 6.3 ( ) Age- and gender-standardized ( ) 1.0 ( ) 6.3 ( ) Age- and education-standardized ( ) 0.9 ( ) 6.4 ( ) 1 Cases per 100 people in a given stratum (95% CI). 2 Adjusted with regard to the population of Seongnam. 3 Standardized with regard to the 2005 Korean population. 272 Jhoo /Kim /Huh /Lee /Park /Lee /Choi / Han /Choo /Youn /Lee /Woo

4 Table 3. Influence of age, gender, and education on the risk of dementia in Korean elders AD VD Dementia OR (95% CI) p OR (95% CI) p OR (95% CI) p Age years years 1.1 ( ) ( ) ( ) years 5.2 ( ) ( ) ( ) years 15.4 ( ) < ( ) ( ) <0.001 Gender Male Female 4.0 ( ) ( ) ( ) Education 7 years years 1.3 ( ) ( ) ( ) OR = Odds ratio. Prevalence (%) Very mild Mild Moderate Severe AD VD Dementia Fig. 1. Prevalence of dementia, AD and VD by severity of dementia per 100 persons aged 65 and older in Seongnam, Korea. Very mild is equivalent to a CDR index of 0.5, mild corresponds to a CDR index of 1, moderate to a CDR index of 2, and severe to a CDR index of 3 or greater. and DLB were estimated to be 3.9% (95% CI = %), 1.0% (95% CI = %), and 0.3% (95% CI = %), respectively. The overall prevalence adjusted with regard to the elderly population of Seongnam was 4.8% for AD (95% CI = %), 1.0% for VD (95% CI = %), 0.4% for DLB (95% CI = %), and 6.2% for overall dementia (95% CI = %) ( table 1 ). As shown in table 2, the prevalence of dementia apparently increased with age. The prevalence of AD increased consistently with advancing age, whereas that of VD peaked at years old and then decreased thereafter. Dementia was more prevalent in women than in men (p = 0.026). This gender difference in the prevalence was significant for AD (OR = 4.0, 95% CI = , p = 0.02) but not VD (OR = 1.1, 95% CI = , p 1 0.1) (table 3 ). The age-adjusted prevalence of AD was 7.0% (95% CI = ) in women and 1.5% (95% CI = ) in men. The influence of the educational level on the prevalence of dementia was not significant in AD or VD after we controlled for the effect of age and gender (p 1 0.1, logistic regression analysis) ( table 3 ). The age- and genderstandardized prevalence of dementia among Korean elderly aged 65 years or older was estimated to be 6.3% for total dementia (95% CI = ), 4.8% for AD (95% CI = ), 1.0% for VD (95% CI = ), and 0.4% for DLB (95% CI = ). Finally, we estimated the age-standardized, severityspecific prevalence of dementia. As shown in figure 1, very mild (CDR = 0.5) and mild (CDR = 1) dementia were more prevalent than the moderate (CDR = 2) and severe (CDR 6 3) type. Among the AD, VD, and overall dementia groups, 71.0, 64.8 and 72.0%, respectively, fell into the very mild and mild stages. Prevalence of Dementia in Korean Elders 273

5 Discussion The age- and gender-standardized prevalence estimate of dementia in our study was 6.3%. Although this figure is slightly higher than those previously reported from the urban populations of other Asian countries, including Japan ( %) [30, 31], China ( %) [4, 32, 33], and India (2.4%) [6], it is lower than that from two previous studies on urban Korean elders (8.2% in the Seoul study [3], 8.0% in the Busan study [2] ). These apparent differences may be due to methodological differences, such as variations among the study designs and diagnostic thresholds for dementia, or they may reflect true population characteristics, such as differences in the incidence of dementia, differential survival and mortality after the onset of the dementia, and/or the demographic structure of the examined society [34]. As we noted previously [3], there is no firm agreement between clinicians or researchers, even when using the same diagnostic criteria, regarding the degree of functional impairment that warrants a diagnosis of dementia. This issue may be one of the major reasons for the differing estimates of dementia across populations. Since the diagnostic procedures and the threshold for dementia in the present study were identical to those used in our prior study in Seoul [3], it may be possible to postulate that the difference in the prevalence estimates between Seongnam and Seoul may be attributed to true differences in the incidence of dementia. Although there is some debate regarding the possible association between low educational attainment and the risk of dementia [35], it seems likely that education may contribute to the risk of dementia at least indirectly. For example, less educated people might be more frequently exposed to toxic drugs or nutritional deficiencies [35]. The proportion of noneducated individuals in the Seongnam population (20.7%) was comparable to that of overall urban areas in Korea, but much lower than that in the Seoul population (44.2%). In addition, low utilization of medical services resulting in poorer control of hypertension, diabetes, and other medical illnesses associated with an increased risk of dementia and high prevalence of alcohol dependency may also have contributed to the difference in the dementia prevalence between these areas [35, 36]. However, this study was not designed to directly test geographical differences in dementia prevalence within Korea, meaning that further studies will be required to test this hypothesis. Consistent with earlier prevalence studies in Korea [2, 3, 10, 11] and other countries [1], we found that the rate of dementia increased exponentially with age. The agestandardized prevalence rate of dementia and its subtypes in the Korean population of 2005 was 6.3%, which is likely to increase since the Korean society is rapidly transforming from an aging society to an aged society. Globally, the number of persons aged 60 years or over is expected to almost triple, and an even more marked increase is expected in the oldest-old populations (persons aged 80 years or over), particularly in developing countries. Currently, the proportion of oldest-old in the Korean population (15.2%) is still much lower than that in other developed countries such as the United States (24.7%) and Japan (19.7%) [37]. The prevalence of AD increased consistently with age, whereas that of VD peaked at the age of years old and decreased thereafter. This finding is consistent with a previous report in a rural elderly population in Korea [10]. Although no prior study has examined stroke and TIA in Korean elders, the prevalence estimates of stroke and TIA have been reported to decrease among the oldest-old [38]. This may be attributed to either a low survival rate or selection bias due to stroke-related physical disabilities. To our knowledge, this is the first report on the prevalence of DLB in community-dwelling Korean elders. DLB has been suggested to be the second most common type of degenerative dementia in older people [12]. In nonpopulation-based studies, prevalence estimates of DLB varied between 3.0 and 26.3% whereas lower estimates of DLB prevalence were found in population-based studies [13 15]. For example, the prevalence of DLB in an elderly Japanese population was estimated to be 0.1% [14]. Consistent with these earlier observations [13 15], the prevalence of DLB in the present study was estimated to be 0.4%, which was lower than that of VD (1.0%). The reported prevalence of AD and VD varies enormously throughout the world. In East Asian countries, an epidemiological transition in the prevalence of dementia whereby the prevalence of AD has become twice that of VD has been observed since the early 1990s [34]. This epidemiological transition in the prevalence of dementia may be due to the modification of risk factors for VD, although there is no clear evidence of a causal relationship for this [34, 35]. Consistent with these earlier observations, we found that AD (4.8%) was more prevalent than VD (1.0%) in our study population. The difference between the prevalence of AD and VD observed in the present study (about 5-fold) was larger than that observed in our previous works from Yonchon (less than 2-fold) [11] and Seoul (about 3-fold) [3]. This may be partly attributed to the higher educational level and socioeconomic 274 Jhoo /Kim /Huh /Lee /Park /Lee /Choi / Han /Choo /Youn /Lee /Woo

6 status of our sample population compared to those in the Yonchon and Seoul studies. One major strength of this study is that we adopted a single-phase design, which avoided the use of dementia screening tests that are susceptible to educational attainment (e.g. the MMSE). In addition, all participants were assessed by expert physicians using standardized, structured instruments for the diagnosis of dementia, stroke, and major psychiatric disorders. These two methodological strengths might have enhanced the accuracy of dementia diagnosis in the present study. However, the present study had two limitations with regard to the study population: first, the sample size was not large enough to estimate the age- and gender-specific prevalence of DLB, and second, the respondent group included younger subjects and fewer women than the nonrespondent group. 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