399

Journal of Alzheimer’s Disease 46 (2015) 399–406 DOI 10.3233/JAD-142790 IOS Press

Body Mass Index and Mortality Rate in Korean Patients with Alzheimer’s Disease Hyemin Janga , Jong Hun Kimb,∗ , Seong Hye Choic , Yunhwan Leed , Chang Hyung Honge , Jee Hyang Jeongf , Hyun Jeong Hang , So Young Moonh , Kyung Won Parki , Seol-Hee Hanj , Kee Hyung Parkk , Hee Jin Kima , Duk L. Naa and Sang Won Seoa,l,m,∗ a Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea b Department of Neurology, Dementia Center, Stroke Center, Ilsan hospital, National Health Insurance Corporation, Goyang-shi, South Korea c Department of Neurology, Inha University School of Medicine, Incheon, Korea d Department of Preventive Medicine and Public Health, Ajou University School of Medicine, Suwon, Korea e Department of Psychiatry, Ajou University School of Medicine, Suwon, Korea f Department of Neurology, Ewha Womans University School of Medicine and Ewha Medical Research Institute, Seoul, Korea g Department of Neurology, Myongji Hospital, Goyang h Department of Neurology, Ajou University School of Medicine, Suwon, Korea i Department of Neurology, Dona-A University College of Medicine, Pusan, Korea j Department of Neurology, Konkuk University College of Medicine, Seoul, Korea k Department of Neurology, Gachon University of Medicine and Science, Gil Medical Center, Incheon l Neuroscience Center, Samsung Medical Center m Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University

Accepted 23 February 2015

Abstract. Background: A relationship between body weight, cognitive impairment, and the onset of Alzheimer’s disease (AD) was recently reported. However, to our knowledge, no studies have investigated the relationship between body weight and mortality in Asian AD patients. Objective: We evaluated the relationship between body mass index (BMI) and mortality rate in Korean AD cohorts. Methods: Participants were consecutively included from two Korean representative registries: 579 AD patients from Samsung Medical Center and 1911 AD patients from the Clinical Research Center for Dementia of South Korea study. We combined these two AD cohorts to evaluate the association between BMI and mortality. BMI was used to categorize the participants into underweight, normal-weight, overweight, and obesity subgroups. All deaths were confirmed through the nationwide mortality database of Statistics Korea. Results: 53 of 181 (29.3%), 208 of 1,127 (18.5%), 88 of 626 (14.1%), and 115 of 556 (20.7%) patients died in the underweight, normal-weight, overweight, and obese subgroups during 43.7 months of follow-up. The time-dependent cox proportional hazards model showed that, relative to the normal-weight subgroup, the underweight group had higher mortality (HR 1.82 (95% CI, 1.07–3.09)) while overweight group had lower mortality rate (HR 0.60 (95% CI, 0.38–0.95)) The effects of underweight and overweight were prominent in younger and older elderly group, respectively. However, there were no interactive effects of dementia severity or gender and BMI on survival rate.

∗ Correspondence to: Jong Hun Kim, MD, PhD, Department of Neurology, Dementia Center, Stroke Center, Ilsan Hospital, National Health Insurance Service, 1232 Baeksok-dong, Ilsandonggu, Koyang-Shi 410-719, South Korea. Tel.: +82 31 900 0213; Fax: +82 31 900 0343; E-mail: [email protected] or Sang Won

Seo, MD PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea. Tel.: +82 2 3410 1397; Fax: +82 2 3410 0052; E-mail: [email protected].

ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved

400

H. Jang et al. / BMI and mortality in AD

Conclusion: Relative to AD patients of normal weight, those who were underweight had an increased mortality rate, and overweight predicted decreased mortality in AD patients. Furthermore, our findings may help facilitate mortality stratification in AD patients by using baseline BMI. Keywords: Alzheimer’s disease, body mass index, mortality, obesity, survival analysis

INTRODUCTION As the world population ages, the prevalence of Alzheimer’s disease (AD) is expected to increase from 26.6 million in 2006 to over 100 million in 2050 [1]. Enormous resources will be required to care adequately for this large number of AD patients. In this context, information about the factors affecting mortality of AD patients is essential for patients, caregivers, clinicians, and policy planners. Such information will be useful for providing the resources needed for adequate institutional and home health care. There has been a tremendous increase in the prevalence of obesity in many countries [2, 3]. Obesity is widely accepted as an important health risk [4] because it is associated with metabolic syndrome components and their complications including type 2 diabetes, hypertension, coronary heart disease, and stroke [5]. However, the relationship between obesity and mortality is complex. For example, underweight consistently predicts increased mortality, whereas the relationship between overweight or obesity and mortality is inconsistent between studies [6–8]. In contrast to the deleterious effects of obesity, it has been reported that obese patients with established diseases have lower mortality rates than their normal-weight peers [9–18]. AD is associated with weight loss [19–21]. These authors have suggested that weight loss may be related to inadequate dietary intake, increased energy expenditure, or AD-related metabolic disturbances. The relationship between body weight and cognitive impairment or the development of AD has been studied extensively. Obesity in midlife is an important risk factor for incident AD [22, 23]. By contrast, in elderly people, underweight predicts the development of dementia [24, 25]. However, the relationship between body weight and AD-related mortality remains unknown. This relationship has been examined in only a few studies of European patients with various dementia disorders [20, 26, 27]. To our knowledge, no studies have reported on the relationship between body weight and mortality in AD patients in Asia, which now has the most rapidly increasing prevalence of AD. It has been suggested that the associations between body mass index (BMI) and health

outcomes may differ between Asian and European populations [28]. In this study, we evaluated the relationship between body weight and mortality in AD patients in combined two Korean AD cohorts. We hypothesized that the risk of mortality would be higher in underweight AD patients and lower in obese AD patients compared with normal-weight AD patients. We also investigated the variables affecting the relationships between BMI and survival rate. MATERIALS AND METHODS Subjects The study participants were consecutively included from two separate registry studies: 725 AD patients from the Memory Disorder Clinic in Samsung Medical Center (SMC, December 1994 to December 2005) and 1,911 AD patients from the Clinical Research Center for Dementia of South Korea (CREDOS) study, a nationwide multicenter cohort study of cognitive disorders involving 31 memory disorder clinics at universities and general hospitals in South Korea (March 2006 to December 2010) [29]. These two studies used a common standardized diagnostic assessment that included the diagnostic criteria for normal cognition amnestic mild cognitive impairment and AD except for scales for activities of daily living. The patients fit the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [30] and the criteria for probable AD proposed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association [31]. All subjects underwent a detailed clinical interview, neurological examination, and comprehensive neuropsychological battery, as described in previous studies [32]. The interview obtained a history of the earliest cognitive behavioral changes and the onset of symptoms, and vascular risk factors as reported by caregivers living with the patient. Blood tests including complete blood count, blood chemistry test, vitamin B12 /folate determination, syphilis serology, and thyroid functioning tests were performed for all subjects.

H. Jang et al. / BMI and mortality in AD

401

Conventional brain MRI scans (T1-weighted, T2weighted, and FLAIR images) confirmed the absence of structural lesions such as territorial infarction, intracranial hemorrhage, brain tumor, hydrocephalus, traumatic brain injury, or severe white matter hyperintensities. The institutional review boards at all participating centers approved this study. Written informed consent was obtained from patients and caregivers.

normal weight was used as a reference group. Among the 725 AD patients from the SMC, 146 patients whose BMI values were missing were excluded. A comparison between the included and excluded patients is shown in Supplementary Table 1. Finally, 579 and 1,911 AD patients from the SMC and CREDOS cohorts were included in this study altogether. The detailed demographic and clinical characteristics of the subjects are shown in Table 1.

BMI

Data collection

BMI was calculated as weight (in kilograms) divided by height (in meters) squared (kg/m2 ) at the first visit or first follow-up visit when patients were diagnosed with AD. The World Health Organization (WHO) guidelines defined underweight as BMIs less than 18.5 kg/m2 , normal between 18.5 and 24.9 kg/m2 , overweight from 25.0 to 29.9 kg/m2 , and obese more than 30.0 kg/m2 . However, Asians generally have a higher percentage of body fat and cardiovascular risk factors than white people of the same BMI. Thus, WHO proposed BMI cut-off points of 23 kg/m2 for overweight which is to identify people with a high risk of health concerns [28]. In this study, all patients were classified into four BMI subgroups based on this recommendations as follows: Less than 18.5 kg/m2 , underweight; 18.5–23 kg/m2 , normal; 23–25 kg/m2 , overweight; and >25 kg/m2 , obesity. A group with

The demographic variables, such as age at symptom onset and at diagnosis, gender, and educational level, were obtained in interviews with the caregivers. Vascular risk factors and comorbidities were also explored. The vascular risk factors included presence of hypertension, diabetes mellitus, history of cardiovascular disease (myocardial infarction, angina pectoris, arrhythmia, and abnormal ECG findings), smoking habits, and alcohol consumption. Hypertension and diabetes mellitus were defined as a reported medical history or documented treatment of either disorder at any time up to the AD diagnosis. Heart disease was defined as a history of myocardial infarction, congestive heart failure, or angina pectoris at any time before or at the time of the AD diagnosis. General cognitive function was evaluated using the Mini-Mental State Examination (MMSE), and clinical assessment

Table 1 Baseline characteristics Demographics Male gender, n (%) Age, years, mean ± SD Age of onset, mean ± SD Deceased, up to 2010.12, n (%) Cardiovascular risk factors, n (%) Hypertension Diabetes Hyperlipidemia Current smoker Coronary artery disease K-MMSE, mean ± SD CDR, mean ± SD Education years, mean ± SD Alcohol intake, n (%) Body mass index, kg/m2 , n (%) BMI

Body Mass Index and Mortality Rate in Korean Patients with Alzheimer's Disease.

A relationship between body weight, cognitive impairment, and the onset of Alzheimer's disease (AD) was recently reported. However, to our knowledge, ...
181KB Sizes 0 Downloads 8 Views