Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease2 (KBASE2) (KBASE2)

Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease2

The KBASE2 is the second phase of the KBASE project, which consists of roll-over participants from the first phase of the KBASE as well as newly enrolled participants with varying degrees of cognitive functions (e.g. individuals with normal cognition, mild cognitive impairment, or AD dementia). In addition to the aims of the first phase of the KBASE, the KBASE2 will focus on new data collection and integrative analysis of the rich structural, functional, and molecular neuroimaging data in relation to whole genome sequencing and other -omics. Network analysis of disruption in brain connectivity in relation to clinical status and AD biomarker profiles also will be conducted.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment

Detailed Description

The Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE) is a comprehensive prospective cohort study launched at Seoul National University (SNU) in 2014 using similar methods to the North American AD Neuroimaging Initiative (ADNI). KBASE includes well-characterized participants with normal cognition (CN), mild cognitive impairment (MCI) and AD dementia. Clinical/cognitive and lifestyle data, multimodal neuroimaging (structural MRI, MR angiography, diffusion tensor imaging, and resting-state fMRI, as well as amyloid, tau and FDG-PET, and bio-specimens were longitudinally collected during the past five years.

The KBASE2, the second phase of the KBASE project, will focus on new data collection and integrative analysis of the rich structural, functional, and molecular neuroimaging data in relation to WGS and other -omics. Network analysis of disruption in brain connectivity in relation to clinical status and AD biomarker profiles in KBASE will be related back to the NIA AD Sequencing Project (ADSP) multi-ethnic dataset (N>20,000) results. Amyloid, tau, neurodegeneration, and cerebrovascular integrity (A/T/N/V) neuroimaging biomarkers will be investigated cross-sectionally and longitudinally. Findings will be contrasted with and validated in independent cohorts, including ADNI and the Indiana Memory and Aging Study (IMAS), which both have similar genetic and deep longitudinal endophenotype data. The overarching premise is that 1) development of precision medicine for ADRD requires systematic multi-modal biomarker collection in diverse cohorts during early at-risk stages of disease to identify diagnostic, prognostic and therapeutic targets, and 2) sophisticated analytic strategies are required to address the complexity of multimodal data, heterogeneity, and diverse participant cohorts. Integrative longitudinal analysis of genetic and -omics networks with structural and functional brain networks in this Asian cohort will yield new targets related to A/T/N/V pathology and other pathways

In KBASE2 projects, the KBASE team at Seoul National University (SNU) and AD research team at Indiana University (ADNI Genetics Core, Indiana ADRC, IU Network Science Institute) will closely collaborate with the ADSP and its multi-institutional working groups, and the Universities of Pennsylvania and Southern California. Whole genome sequences (WGS) will be ADSP-harmonized by the NIA Genomic Center for AD (GCAD) and shared via NIAGADS (both UPenn). The Laboratory of Neuroimaging (LONI; USC) will support imaging and related data sharing.

• Study Type: Observational
• Enrollment (Estimated): 640

Contacts and Locations

• Study Contact: Name: Dong young Lee, MD, PhD; Phone Number: +82-2-2072-2205; Email: selfpsy@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Principal Investigator: Dong Young Lee, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • SMG-SNU Boramae Medical Center
    • Contact: Jun-Young Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Young and elderly normal controls: community-based population AD and MCI: clinic or community-based population

Description

Participants will be classified as either Alzheimer's disease(AD) group, mild cognitive impairment(MCI) group, elderly normal controls or young normal controls. Specific inclusion criteria for each group is described below.

Inclusion Criteria:

[Inclusion criteria: AD]

• Age : 55 - 90
• Clinical Dementia Rating (CDR)=0.5 or 1
• Diagnostic and Statistical Manual-IV(DSM-IV) criteria for dementia
• National Institute of Aging and the Alzheimer's Association (NIA-AA) Probable AD dementia
• Study partner or caregiver to accompany patient to all scheduled visits
• Written informed consent

[Inclusion criteria: MCI (amnestic)]

• Age : 55 - 90
• Clinical Dementia Rating (CDR)=0.5
• Concern regarding a change in cognition (obtained from the subject, from an informant who knows the subject, or from a skilled clinician observing the subject)
• Lower performance in any cognitive domain that is greater than would be expected for the subject's age and educational background
• Preservation of independence in functional abilities
• Study partner or caregiver to accompany subject to all scheduled visits
• Written informed consent

[Inclusion criteria: Elderly normal controls]

• Age : 55 - 90
• Clinical Dementia Rating (CDR)=0
• Those with contactable Informant
• Written informed consent

[Inclusion criteria: Young normal controls]

• Age : 20 - 54
• Clinical Dementia Rating (CDR)=0
• Written informed consent

Exclusion Criteria:

[Exclusion criteria: general]

• Past history or presence of major psychiatric illness (e.g. schizophrenia, bipolar disorder, alcohol/substance abuse or dependence, delirium)
• Significant neurologic or medical condition that can influence the mental state
• Contraindications for MRI scan (e.g. pacemaker, claustrophobia)
• Illiteracy
• Significant visual or hearing difficulty
• Taking investigational drug
• In pregnancy or breast-feeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Young normal controls; age : 20 ~ 54; without dementia, MCI, or other major neurological/psychiatric illness
Elderly normal controls; age : 55 ~ 90; without dementia, MCI, or other major neurological/psychiatric illness
MCI (Mild cognitive impairment); age : 55 ~ 90; without major neurological/psychiatric illness; concern regarding a change in cognition, lower performance in any cognitive domain that is greater than would be expected for the subject's age and educational background and preservation of independence in functional abilities
AD (Alzheimer's diseases); age: 55 ~ 90; National Institute of Aging and the Alzheimer's Association (NIA-AA) Probable AD dementia(Alzheimer's diseases)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of brain amyloid deposition	Group difference in baseline brain amyloid deposition on florbetaben PET and the relationship between the amount of brain amyloid deposition and clinical, neuropsychological, neuroimaging, genetic, biochemical measurement will be investigated.	baseline
Amount of brain tau deposition	Group difference in baseline brain amyloid deposition on AV1451 PET and the relationship between the amount of brain tau deposition and clinical, neuropsychological, neuroimaging, genetic, biochemical measurement will be investigated.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of brain amyloid deposition	The change of brain amyloid deposition and its relation to the clinical, neuropsychological, neuroimaging, genetic and biochemical variables will be assessed.	2 years
Change of brain tau deposition	The change of brain tau deposition and its relation to the clinical, neuropsychological, neuroimaging, genetic and biochemical variables will be assessed.	2 years
Change of CERAD total score	The change of CERAD total score and its relation to neuroimaging, genetic and biochemical variables will be assessed.	2 years
Change of cortical thickness	The change of Alzheimer-signature region cortical thickness and its relation to neuroimaging, biochemical, genetic biomarkers will be assessed	2 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Dong Young Lee, MD, PhD, Department of Psychiatry, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: October 23, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Alzheimer Disease; Neuroimaging; Prediction; Early diagnosis; Multiomics; Network-based analysis; Systems biology
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: KBASE02; U01AG072177 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No