ORIGINAL ARTICLE Print ISSN 1738-3684 / On-line ISSN 1976-3026 https://doi.org/10.4306/pi.2017.14.6.851 OPEN ACCESS Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease: Methodology and Baseline Sample Characteristics Min Soo Byun1, Dahyun Yi1, Jun Ho Lee2, Young Min Choe3, Bo Kyung Sohn4, Jun-Young Lee5,6, Hyo Jung Choi5, Hyewon Baek7, Yu Kyeong Kim8, Yun-Sang Lee9, Chul-Ho Sohn10, Inhee Mook-Jung11,12, Murim Choi12, Yu Jin Lee2,6, Dong Woo Lee4, Seung-Ho Ryu13, Shin Gyeom Kim14, Jee Wook Kim15, Jong Inn Woo6, Dong Young Lee1,2,6 , and for the KBASE Research Group* 1Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea 2Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea 3Department of Neuropsychiatry, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea 4Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea 5Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea 6Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea 7Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Yongin, Republic of Korea 8Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea 9Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea 10Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea 11Department of Biochemistry, Seoul National University College of Medicine, Seoul, Republic of Korea 12Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea 13Department of Psychiatry, School of Medicine, Konkuk University, Konkuk University Medical Center, Seoul, Republic of Korea 14Department of Neuropsychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea 15Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea ObjectiveaaThe Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimer’s disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. MethodsaaAll participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [11C]Pittsburgh compound B-positron emission tomography (PET), and [18F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitor- ing and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannu- ally with the full KBASE assessment, including neuroimaging and laboratory tests. ResultsaaAs of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants–291 cogni- tively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)–were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. ConclusionaaThe KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the re- cruitment, study methodology, and baseline sample characteristics are described in this paper. Psychiatry Investig 2017;14(6):851-863 Key Wordsaa Alzheimer’s disease, Early diagnosis, Prediction, Biomarker, Prospective cohort study. Received: April 17, 2017 Revised: June 27, 2017 Accepted: July 8, 2017 Available online: October 12, 2017 Correspondence: Dong Young Lee, MD, PhD Department of Neuropsychiatry, Seoul National University Hospital, Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-ro, Jong- no-gu, Seoul 03080, Republic of Korea Tel: +82-2-2072-2205, Fax: +82-2-744-7241, E-mail: [email protected] *Information on the KBASE Research Group is provided in the Supplementary Materials 2 (in the online-only Data Supplement). cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2017 Korean Neuropsychiatric Association 851 Methodology and Baseline Characteristics of KBASE INTRODUCTION are expensive and are not commonly available except at ter- tiary hospitals, but they also come with the risk of radiation ex- Alzheimer’s disease (AD) is the most common cause of de- posure for serial or repeated scans.17,19,20 Additionally, clinical mentia.1,2 Because older age itself is a primary risk factor for interpretations of neuroimaging-based neuronal injury bio- AD, the number of people living with AD is increasing rap- markers are mostly dependent on visual qualitative reading idly and is projected to reach over 100 millions worldwide by because of limited normative information for quantitative read- 2050, resulting in tremendous social and economic impacts ing, particularly in non-Caucasian population.21 Thus, less in- globally.2-4 Development of effective therapeutic interventions vasive, less expensive, more readily available “new” biomark- that can delay or prevent disease progression has become a ers that are highly accurate and reliable for AD are needed, public health priority, notably since previous studies postu- especially given increasing need for biomarkers that can be lated that the prevalence and economic burden of AD could used on the front line in widespread screening in clinical prac- decrease by almost 50% in 2050 if the onset of AD is delayed tice and for the recruitment of candidates for clinical trials, as by 5 years in 2015.5,6 well as for repeated use for monitoring disease progression Nevertheless, the underlying etiologies and pathophysiolo- and treatment efficacy. For example, blood-based biomarkers gy of AD are not yet fully understood and there is currently no that can be assessed with simple venipuncture will be candi- effective treatment that can cure AD. Moreover, recent clinical dates if they reflect the underlying AD pathology.17 Several trials using anti-amyloid therapies for mild-to-moderate AD previous studies have attempted to discover novel biomark- dementia (ADD) patients that were expected to modify the ers for AD from blood-derived specimens (i.e., plasma, DNA, disease-course of AD failed to meet the primary endpoints.7-9 etc.) along with advancements in analytical methods such as Regarding the disappointing outcome of these trials, research- proteomic and genetic analyses.17,22-25 The previously report- ers pointed out that the timing of intervention may have been ed candidates, however, have limited utilization due to vari- one of the possible reasons; for patients with dementia stage able accuracy and low reproducibility stemming from two of AD, it may be too late for disease-course modification be- factors: 1) for several studies, samples were collected based cause of the irreversible neuronal loss that would mitigate on clinical diagnosis criteria rather than presence of in vivo any effect of therapy.8,10 Thus, early detection and intervention AD pathologies and 2) sample sizes were relatively small for before neuronal loss are likely to be important for maximiz- some studies. Therefore, further large-scale, well-character- ing the beneficial effect of new therapies. Furthermore, the tar- ized cohort studies are necessary to discover and validate bio- gets for developing disease-modifying agents are shifting from markers including blood-based ones that can reflect in vivo patients with ADD to individuals in the predementia phase brain AD pathologies. and even in the asymptomatic stage of AD.11 In this context, Various risk or protective factors for dementia syndrome development and validation of AD biomarkers for the early or cognitive impairment have been suggested by numerous detection and prediction of AD with high accuracy have be- epidemiological studies.1,26 However, we still do not know come important research goals.12,13 much about the mechanisms through which various lifetime Several neuroimaging techniques including positron emis- experiences such as physical and mental activity, social rela- sion tomography (PET) and magnetic resonance imaging (MRI) tionships, stress experiences, personality, diet and nutrition, and cerebrospinal fluid (CSF) biomarkers that reflectβ -amyloid and sleep, and many aging-related physiological or patholog- (Aβ) deposition and AD-specific neurodegeneration are cur- ical changes in the human body, such as vascular status, hor- rently available.12-14 Although these biomarkers have mark- monal changes, glucose or lipid metabolism, and body mass edly advanced clinical research and practice regarding AD