Korean Joint Registry for Alzheimer's Treatment and Diagnostics (JOY-ALZ) (JOY-ALZ)

The purpose of this research is to investigate the long-term effectiveness and safety of new Alzheimer's disease treatments, particularly monoclonal antibody therapies like lecanemab and donanemab, as well as to enhance diagnostic methods for Alzheimer's disease by collecting real-world data from Korean Alzheimer's patients. The goal is to contribute to the precision of Alzheimer's treatment and to evaluate the impact of these new therapies and diagnostic techniques in clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer Disease; Mild Cognitive Impairment; Subjective Cognitive Decline (SCD)

Detailed Description

In 2024, it is estimated that there will be over 1 million individuals aged 65 and older with dementia in South Korea, with national dementia care costs exceeding approximately 17 trillion KRW (0.9% of GDP). South Korea is experiencing rapid population aging, leading to a projected significant increase in both the number of patients and the associated socio-economic costs. Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment in the elderly, characterized by the abnormal accumulation of amyloid beta (Aβ) and tau proteins in the brain. Research has shown that beta-amyloid protein begins to accumulate in the brain over 20 years before the onset of memory impairment symptoms. Consequently, Alzheimer's disease progresses through a prolonged asymptomatic stage of normal cognitive function (cognitively unimpaired, CU) to subjective cognitive decline, mild cognitive impairment, and dementia.

In May 2024, the Korean Ministry of Food and Drug Safety approved lecanemab for the treatment of Alzheimer's disease. Recent advancements have been made in the development of new treatments and diagnostic methods for Alzheimer's disease, with some already approved for use in South Korea or anticipated to receive approval soon. These developments are expected to significantly impact the management of dementia and cognitive impairment patients in the near future. Among the new treatments, monoclonal antibody injections targeting the core pathological mechanism of Alzheimer's disease, which is the removal of beta-amyloid protein (e.g., lecanemab, donanemab), currently lack long-term efficacy data, providing only 1-2 years of investigatory data in clinical trials. Such medications may have side effects, including amyloid-related imaging abnormalities (ARIA) such as brain edema or microbleeding and infusion-related adverse reactions. For the advancement of precise treatments for Alzheimer's disease, it is essential to monitor long-term effects and side effects of these drugs in clinical practice to collect and analyze more extensive clinical data to establish additional clinical evidence.

Moreover, the phase 3 clinical trial data for lecanemab suggests that the drug's effectiveness and side effects may vary by ethnicity. Recently, a diagnostic technique that measures Elecsys beta-amyloid 42 (Aβ42) and Elecsys Phospho-Tau181 (ptau181) in cerebrospinal fluid (CSF) has received approval from the Korean Ministry of Food and Drug Safety for the diagnosis of Alzheimer's disease. Additionally, there is a strong potential for new diagnostic methods that measure proteins such as ptau217, ptau181, and Aβ42 in blood to be commercialized in clinical practice. Future advancements through real-world data collection on these new diagnostic methods will be necessary.

The Alzheimer's Association (AA) and researchers in the United States have initiated a registry study named the Alzheimer's Network for Treatment and Diagnostics (ALZ-NET) to collect real-world data on new treatments and diagnostic methods for Alzheimer's disease. Longitudinal studies to investigate the long-term effectiveness and safety of new treatments and diagnostic methods in Alzheimer's patients are also being established in countries such as Japan, Australia, the Netherlands, and Europe. In response to these changes in Alzheimer's disease management, the researchers aim to contribute to the precision of Alzheimer's treatment and the enhancement of new diagnostic methods by collecting real-world data from Korean Alzheimer's patients regarding the long-term effectiveness and safety of new therapies.

• Study Type: Observational
• Enrollment (Estimated): 4000

Contacts and Locations

• Study Contact: Name: Geon-ha Kim; Phone Number: 82-2-587-7462; Email: geonha@ewha.ac.kr

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
    • Contact: Kee-hyung Park; Phone Number: 82-2-587-7462; Email: khpark@gachon.ac.kr
    • Contact: Kee-hyung Park
  • Incheon, Korea, Republic of, 22332
    • Recruiting
    • Inha University Hospital
    • Contact: Seonghye Choi; Phone Number: 82-2-587-7462; Email: seonghye@inha.ac.kr
    • Contact: Seong-hye Choi
  • Seoul, Korea, Republic of, 07985
    • Not yet recruiting
    • Ewha Womans University Mokdong Hospital
    • Contact: Geon-ha Kim; Phone Number: 82-2-587-7462; Email: geonha@ewha.ac.kr
    • Contact: Geon-ha Kim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Approximately 40 medical institutions nationwide are expected to participate in the study over a period of 10 years, with about 4,000 participants in total. Our institution anticipates the participation of approximately 100 subjects. Participants in this study are adults with Alzheimer's disease dementia, mild cognitive impairment, or normal cognitive function (including subjective cognitive decline) who are undergoing medical evaluation for newly approved Alzheimer's disease medications after 2021, have made the decision to initiate treatment with these medications, or have already begun treatment with these newly approved Alzheimer's disease medications.

Description

Inclusion Criteria:

1. Participants must be 19 years of age or older at the time of informed consent.
2. Patients who are undergoing medical evaluation for newly approved Alzheimer's disease medications after 2021, patients who have decided to initiate treatment with these medications in consultation with their physician after 2021, or patients who have already started treatment with newly approved Alzheimer's disease medications after 2021.
3. Patients who have undergone an amyloid PET scan to confirm Alzheimer's disease pathology, or cerebrospinal fluid testing for Aβ42 and ptau181.
4. Clinical diagnosis of Alzheimer's disease, defined as follows:

1. [Alzheimer's Disease Dementia (ADD)] - Must meet the criteria for probable Alzheimer's dementia as defined by the National Institute on Aging and the Alzheimer's Association working groups (NIA-AA).

   • Must exhibit cognitive decline that impairs independent daily living.

2. [Mild Cognitive Impairment (MCI)]

   - Must meet NIA-AA diagnostic criteria for MCI.

   - The subject or informant must report cognitive decline.

   - Performance on delayed recall of verbal memory must be more than -1.0 SD below the age- and education-adjusted normative mean, or scores on any one or more tests of executive function, language, visuospatial abilities, or attention must be more than -1.5 SD below the age- and education-adjusted normative mean.

   - Clinical Dementia Rating scale (CDR) of 0.5.

   - Maintenance of independent daily living ability.

   - Not categorized as dementia.

3. [Cognitively Unimpaired (CU)]

   - Delayed recall of verbal memory must be at or above -1.0 SD versus the age- and education-adjusted normative mean, and all executive function, language, visuospatial abilities, and attention tests must be at or above -1.5 SD versus the age- and education-adjusted normative mean.

   - Maintenance of independent daily living ability.

   • If the subject reports cognitive decline, they will be classified as having Subjective Cognitive Decline (SCD).

     5. Patients must be ambulatory (use of mobility aids is acceptable). 6. The subject must provide written informed consent to participate in the study. In the case of dementia patients, additional written consent from a guardian is required.

Exclusion Criteria:

1. Presence of significant psychiatric disorders associated with intellectual disability, schizophrenia, major depression, bipolar disorder, delirium, etc.
2. History of substance abuse or alcohol dependence that required treatment within the past five years.
3. A current diagnosis of cancer that has not achieved remission within the past five years. However, localized prostate cancer, cervical carcinoma in situ, non-melanoma skin basal cell carcinoma, or squamous cell carcinoma are excluded.
4. Evidence of severe or unstable physical conditions (e.g., dialysis, severe liver disease).
5. Visual or auditory impairments that prevent the satisfactory assessment of cognitive function.
6. Inability to perform MRI due to the presence of metallic substances in the body.
7. Currently participating in another drug clinical trial.
8. Currently pregnant or breastfeeding.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Open Label Registry; Collection of real-world data from enrolled patients being evaluated for or receiving novel Korea MFDS-approved Alzheimer's disease treatments and diagnostics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Korean Mini-Mental State Examination-2 (K-MMSE-2) total score	This test consists of orientation to time and place, three-word recall, subtracting 7 from 100 in succession, overlapping pentagon drawing, command execution, reading, writing, repeating, and naming. The score ranges from 0 to 30.	Up to 10 years
Change from baseline in the Korean version of Montreal Cognitive Assessment (K-MOCA) total score	This assessment evaluates memory, language, executive function, visuospatial construction, reasoning, and attention, with a scoring range of 0-30 points where higher scores indicate better cognitive function.	Up to 10 years
Change from baseline in the Clinical Dementia Rating scale (CDR) total score	Scores include a Global CDR (0-3 points) and a CDR-Sum of Boxes (SB) which sums the scores of the six domains (0-18 points). Higher scores indicate worse cognitive function.	Up to 10 years
Change from baseline in the Functional Assessment Questionnaire (FAQ) total score	The informant evaluates the subject, with a score range of 0-30, where higher scores indicate a decline in daily functioning. A score of 9 or more suggests significant deterioration in daily functioning.	Up to 10 years
Change from baseline in the Korean version of the Alzheimer disease 8 (K-AD8) total score	The score ranges from 0 to 8, where higher scores indicate more severe cognitive impairment.	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Magnetic Resonance Imaging (MRI)	Data will be collected to diagnose cognitive impairment and to assess for emergence of amyloid related imaging abnormalities.	Up to 10 years
Alzheimer's disease (AD) biomarkers	Data from past amyloid Positron Emission Tomography (PET) scans will be collected for the diagnosis of AD. Results for cerebrospinal fluid assays of Elecsys Aβ42, Elecsys ptau181, and ptau181/Aβ42 will also be collected. A ptau181/Aβ42 ratio greater than 0.023 indicates a suggestion of AD.	Up to 10 years

Collaborators and Investigators

• Sponsor: Ewha Womans University Mokdong Hospital
• Collaborators: Samsung Medical Center; Seoul St. Mary's Hospital, The Catholic University; Asan Medical Center; Chonnam National University Hospital; Seoul National University Hospital; Gachon University Gil Medical Center; Gangnam Severance Hospital; CHA University; Soonchunhyang University Hospital; Jeju National University Hospital; Saint Vincent's Hospital, Korea; Chungnam National University Hospital; Wonkwang University Hospital; Konkuk University Hospital; Kyunghee University Medical Center; Inha University Hospital; KangWon National University Hospital; Ewha Womans University Seoul Hospital; Bundang Seoul National University Hospital; Ajou University Hospital, Suwon, South Korea; Busan University Medical Center; InjeUniversityBusanPaikHospital; Korean Dementia Association; Korea University Medicine; Yonsei University Yongin Severance Hospital; Gyungbook national university hospital; Hanllym University Medical Center; Heavenly Clinical Research
• Investigators: Principal Investigator: Geon-ha Kim, Ewha Womans University Mokdong Hospital; Principal Investigator: Seong-hye Choi, Inha University Hospital; Principal Investigator: Kee-hyung Park, Gachon University Gil Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Lecanemab; Real World Data
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: JOY-ALZ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with Eisai and gAAIN.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No