Korea Alzheimer's Disease Neuroimaging Initiative (K-ADNI)

PRIMARY OBJECTIVES

-Establish a registry for Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD)

STUDY DESIGN

-This is a non-randomized, natural history, observational, registry study.

SAMPLE SIZE AND RECRUITMENT

- Five hundred subjects will be enrolled at each clinical site (50 NC, 200 with MCI, 50 with AD, 100 with vMCI, and 100 with SIVD)

SUMMARY OF KEY ELIGIBILITY CRITERIA

• Newly enrolled subjects will be between 50-80 (inclusive) years of age.
• 1) Cognitively Normal Subjects
• 2) MCI subjects
• 3) AD subjects
• 4) vMCI or SIVD

PROCEDURES

• Recruited subjects will have clinical/cognitive assessments, biomarker and genetic sample collection, and imaging.
• Subjects will be followed up for 36 months from the baseline visit. All assessments are to be performed every year from baseline(0, 12, 24, 36 months), except; 1) FDG-PET and amyloid-PET will be performed every two years, i.e., on baseline and at 24 month visit. 2) CSF collection will also be performed on baseline and at 24 months visit. 3) Clinical/cognitive assessment and MRI evaluation will additionally be done at 6 months from baseline to determine short term change.

OUTCOME MEASURES

• Group differences for each clinical, cognitive, biochemical, and imaging measurement.
• Rate of conversion or change of disease severity will be evaluated among all groups
• Correlations among biomarkers and biomarker changes

Study Overview

• Status: Unknown
• Conditions: Mild Cognitive Impairment; Alzheimer's Disease; Subcortical Vascular Dementia

Detailed Description

The major goals of K-ADNI are to:

1. Establish a registry for Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD)

   • Collect longitudinal clinical, imaging, genetic, and biochemical biomarker data for clinical and neuroscience studies on 500 subjects in five diagnostic categories: cognitively normal control (NC), mild cognitive impairment (MCI), mild AD, vascular MCI (vMCI), and SIVD.
   • The following measurements known as representative parameters of dementia progress will be included. 1) clinical characteristics, 2) neuropsychological test, 3) structural and functional magnetic resonance image (MRI), 4) Fludeoxyglucose (FDG)-positron emission tomography (PET), 5) amyloid PET (18F-flutemetamol), 6) cerebrospinal fluid (CSF) and blood sample, 7) genetic analysis.

2. Determination of factors that are crucial in the aggravation or deterrence of progress of dementia syndrome, so that these factors can be used as predictors and outcome measures of AD and SIVD

   • Determine the relationships among clinical, imaging, genetic, and biochemical biomarker characteristics of the entire spectrum of AD, as the pathology evolves from normal aging through very mild symptoms, to MCI, and finally to dementia.
   • Also, determine the relationship among clinical, imaging, genetic, and biochemical biomarker characteristics of the vascular MCI (vMCI) and SIVD, which is an important sub-population of dementia syndrome especially in Asian population.

3. Identification of surrogate markers for new drug development in patients with AD and SIVD

   - Identify prognostic markers of AD and SIVD, identify outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios for new drugs.

4. Development of the standard model for acquiring multi-site neuroimaging study data - Develop improved methods which will lead to uniform standards for acquiring longitudinal multi-site clinical, MRI, PET, and other biological markers (blood, CSF, gene) data on patients with AD, MCI, vMCI, SIVD, and elderly controls.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120752
    • Seong Yoon Kim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Community Sample

Description

Inclusion Criteria:

1. Cognitively Normal Subjects

   • Mini-Mental State Examination (MMSE) scores between 24-30 (inclusive)
   • Clinical Dementia Rating (CDR)=0
   • non-depressed (Geriatric Depression Scale scores less than 4)
   • no evidence of cognitive impairment

2. MCI subjects

   • MMSE scores between 24-30 (inclusive)
   • a subjective memory concern reported by subject, informant, or clinician
   • objective memory loss measured by age and education year adjusted scores on logical memory sub-test (below -1.5 SD)
   • CDR=0.5
   • preserved activities of daily living, and an absence of dementia.

3. AD subjects

   • MMSE scores between 20-26 (inclusive)
   • CDR= 0.5 or 1.0.
   • meets National Institute of Neurological and Communicative Disorders and Stroke / Alzheimer's Disease and Related Disorders Associations (NINCDS/ADRDA) criteria for probable AD

4. vMCI or SIVD

   • For diagnosis of vMCI or SIVD, it is necessary to meet the above clinical/cognitive test scores of MCI or AD.
   • Presence of vascularity are determined by; 1) more than 2 vascular risk factors in recent 5 years (hypertension, diabetes, stroke, dyslipidemia, other cardiovascular disease, obesity, lack of exercise, and smoking) AND 2) more than 1 evidence of vascular neurological symptom, sign, or history AND 3) neuroimaging evidence of white matter hyperintensity, which is rated moderate or severe on MR T2-weighted image(T2WI) or FLAIR images.

Exclusion Criteria:

• Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions; Participants with multiple lacunes or lacunes in a critical memory structure are excluded
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
• Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past 1 year
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder
• History of schizophrenia
• History of alcohol or substance abuse or dependence within the past 2 years
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
• Any significant neurologic disease such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
cognitively normal; MRI scans, PET scans, lumbar puncture
mild cognitive impairment; MRI scans, PET scans, lumbar puncture
Alzheimer's Disease; MRI scans, PET scans, lumbar puncture
vascular MCI; MRI scans, PET scans, lumbar puncture
subcortical ischemic vascular dementia; MRI scans, PET scans, lumbar puncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of dementia conversion or disease severity worsening, evaluated by neuropsychological, MRI, PET, biomarker indices.	- The rate of decline as measured by clinical dementia rating (CDR) Sum of Boxes	0 Months (Baseline), 6 Mos, 12 Mos, 24 Mos, 36 Mos

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in cognitive, neuroimaging, and biomarker assessments	The rate of decline as measured by cognitive tests, Activities of Daily Living; The rate of volume change of the whole brain, hippocampus, and other structural MRI measures; Rates of change of glucose metabolism (FDG-PET); Extent of amyloid deposition as measured by 18F-flutemetamol; Correlations among biomarkers and biomarker changes; Group differences for each imaging and biomarker measurement	0 Months (baseline), 6 Mos, 12 Mos, 24 Mos, 36 Mos

Collaborators and Investigators

• Sponsor: Korean Alzheimers' Disease Neuroimaing Intitiative
• Investigators: Principal Investigator: Seong Yoon Kim, MD, PhD, Asan Medical Center, Univ. of Ulsan, Medical College

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ANTICIPATED): October 1, 2020
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: October 21, 2013
• First Submitted That Met QC Criteria: October 31, 2013
• First Posted (ESTIMATE): November 8, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2019
• Last Update Submitted That Met QC Criteria: March 7, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: dementia; amyloid; plaques; neuroimaging; biomarkers; cognition disorder; early detection; pre-dementia; Alzheimer's disease; mild cognitive impairment; subcortical Vascular Dementia; vascular MCI
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Cognition Disorders; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Dementia; Alzheimer Disease; Cognitive Dysfunction; Dementia, Vascular
• Other Study ID Numbers: HI12C0713